ISSN 1300-3124
PERINATAL
JOURNAL
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The Official Publication of
Perinatal Medicine Foundation
Turkish Perinatology Society
Turkish Society of Obstetrics and Gynecology
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Volume 23 | Issue 1 | April 2015
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www.perinataljournal.com
The Official Publication of Perinatal Medicine Foundation,
Turkish Perinatology Society and
Turkish Society of Ultrasound in Obstetrics and Gynecology
Description
Perinatal Journal, the Official Publication of Perinatal Medicine
Foundation, Turkish Perinatology Society and Turkish Society of
Ultrasound in Obstetrics and Gynecology, is an international online
open access peer-reviewed scientific journal (e-ISSN: 1305-3124)
published triannually in English. The manuscripts which are accepted for publication in the Perinatal Journal are published as a parallel
publication of Turkish version in “Perinatoloji Dergisi” (p-ISSN:13005251, e-ISSN:1305-3132). Translation in to Turkish language is provided by the publisher as free of charge for authors. This is automatically accepted by the authors of manuscripts at the time of submission.
The journal mainly includes original clinical and experimental
research articles, case reports, reviews, editorial and opinion articles,
and a letters column. Perinatal Journal can be read by perinatologists, obstetricians, gynecologists, radiologists, pediatricians, sonographers, midwives, radiographers, and scientific members of other
related areas.
Aim and Scope
Perinatal Journal aims to create an interdisciplinary scientific platform for sharing and discussing topics on perinatal medicine and to
share its experience with international scientific community.
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Periantal Journal does not officially agree with the ideas of manuscripts published in the journal and does not guarantee for any product or service advertisements in its content. Scientific and legal
responsibilities of published articles belong to their authors.
Materials such as pictures, figures, tables etc. sent with manuscripts
should be original or if they were published before written approval
of copyright holder should be sent with manuscript for publishing
together.
All published materials will become the sole property of, and will
be copyrighted by Perinatal Journal. Therefore, "Acknowledgement
of Authorship and Transfer of Copyright Agreement" are requested
in addition to manuscripts that are to be assessed.
Acknowledgement of Authorship and Transfer of Copyright
Agreement form is available online at www.perinataljournal.com.
No payment is done for manuscripts under the name of copyright or
others approved for publishing in the journal and no publication cost
is charged.
Deomed Publishing
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Telefon: +90 216 414 83 43 (Pbx) Faks: +90 216 414 83 42
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The authors should disclose all issues concerning financial relationship, conflict of interest, and competing interest that may potentially influence the results of the research or scientific judgment. All
financial contributions or sponsorship, financial relations, and areas
of conflict of interest should be clearly explained in the cover letter
to the Editor-in-Chief at the time of submission, with full assurance
that any related document will be submitted to the journal when
requested. For the details of journal's "Conflicts of Interest Policy"
please visit www.perinataljournal.com.
Publication Ethics and Malpractice Statement
For the details of journal's “Publication Ethics and Malpractice
Statement” please visit www.perinataljournal.com.
Publication Info
Ownership: On behalf of the Perinatal Medicine Foundation,
Cihat fien
Managing Editor: Murat Yayla
Administrative Office: Cumhuriyet Cad. 30/5 Elmada¤, Taksim
34367 ‹stanbul
Due the Press Law of Turkish Republic dated as June 26, 2004 and
numbered as 5187, this publication is classified as a local periodical. Perinatal Journal is published by Deomed Publishing (Copyright
© 2015, Perinatal Medicine Foundation).
Publication Coordinator: ‹lknur Demirel
English Editor: Fikret Yeflilyurt
Graphic Design: Tolga Erbay
Page Layout: Nurgül Özcan
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www.perinataljournal.com
Volume 23 | Issue 1 | April 2015
Editor-in-Chief
Advisory Board
Cihat fien,
Istanbul, Turkey
Abdallah Adra, Beirut, Lebanon
Arif Akflit, Eskiflehir, Turkey
Aris Antsaklis, Athens, Greece
Saadet Arsan, Ankara, Turkey
Abdel-Latif Ashmaig, Khartoum, Sudan
Alev At›fl-Ayd›n, Istanbul, Turkey
Ahmet Baschat, Baltimore, MD, USA
Ahmet Baflaran, Konya, Turkey
Lous Cabero Roura, Barcelona, Spain
Manuel Carrapato, Porto, Portugal
Jose M. Carrera, Barcelona, Spain
Julene Carvalho, London, UK
Rabih Chaoui, Berlin, Germany
Frank Chervenak, New York, NY, USA
Bülent Çakmak, Tokat, Turkey
Filiz Çayan, Mersin, Turkey
Ebru Çelik, Malatya, Turkey
Vincenzo D’Addario, Bari, Italy
Nur Daniflmend, Istanbul, Turkey
Cansun Demir, Adana, Turkey
Jan Deprest, Leuven, Belgium
Ebru Dikensoy, Gaziantep, Turkey
Gian Carlo DiRenzo, Perugia, Italy
Tony Duan, Shanghai, PRC
Joachim Dudenhausen, Berlin, Germany
Alaa Ebrashy, Cairo, Egypt
Elif Gül Yapar Eyi, Ankara, Turkey
Ali Gedikbafl›, Istanbul, Turkey
Ulrich Gembruch, Bonn, Germany
Anne Greenough, London, UK
Gökhan Göynümer, Istanbul, Turkey
Arif Güngören, Hatay, Turkey
Melih A. Güven, Istanbul, Turkey
Joseph Haddad, Paris, France
Davor Jurkovic, London, UK
Oliver Kagan, Tübingen, Germany
Ömer Kandemir, Ankara, Turkey
Burçin Kavak, Elaz›¤, Turkey
‹schiro Kawabata, Osaka, Japan
Selahattin Kumru, Düzce, Turkey
Mertihan Kurdo¤lu, Ankara, Turkey
Associate Editors
Murat Yayla,
Istanbul, Turkey
Olufl Api,
Istanbul, Turkey
As›m Kurjak, Zagreb, Croatia
Nilgün Kültürsay, Izmir, Turkey
Malcome Levene, Leeds, UK
Narendra Malhotra, Agra, India
Giampaolo Mandruzzato, Trieste, Italy
Alexandra Matias, Porto, Portugal
Ratko Matijevic, Zagreb, Croatia
Israel Meizner, Tel Aviv, Israel
Mohammed Momtaz, Cairo, Egypt
Giovanni Monni, Cagliari, Italy
Ercüment Müngen, Istanbul, Turkey
Kypros Nicolaides, London, UK
Lütfü Öndero¤lu, Ankara, Turkey
Soner R. Öner, Izmir, Turkey
Okan Özkaya, Isparta, Turkey
Alexander Papitashvilli, Tbilisi, Georgia
‹brahim Polat, Istanbul, Turkey
Ritsuko Pooh, Osaka, Japan
Ruben Quintero, Tampa, FL, USA
Nebojsa Radunovic, Belgrade, Serbia
Guiseppe Rizzo, Rome, Italy
Stephen Robson, Newcastle, UK
Roberto Romero, Detroid, MI, USA
Levent Salt›k, Istanbul, Turkey
Haluk Sayman, Istanbul, Turkey
Mekin Sezik, Isparta, Turkey
Jiri Sonek, Dayton, OH, USA
Yunus Söylet, Istanbul, Turkey
Milan Stanojevic, Zagreb, Croatia
Florin Stomatian, Cluj, Romania
Turgay fiener, Eskiflehir, Turkey
Alper Tanr›verdi, Ayd›n, Turkey
Ebru Tar›m, Adana, Turkey
Neslihan Tekin, Eskiflehir, Turkey
Ilan Timor-Tritsch, New York, NY, USA
Seyfettn Uluda¤, Istanbul, Turkey
Liliana Voto, Buenos Aires, Argentina
Miroslaw Wielgos, Warsaw, Poland
Simcha Yagel, Tel Aviv, Israel
Ahmet Yal›nkaya, Diyarbak›r, Turkey
Ivica Zalud, Honolulu, HI, USA
Names are in alphabetical order.
The Official Publication of Perinatal Medicine Foundation, Turkish Perinatology Society
and Turkish Society of Ultrasound in Obstetrics and Gynecology
Correspondence: Perinatal Journal, Perinatal Medicine Foundation,
Cumhuriyet Cad. 30/5 Elmada¤, Taksim 34367 ‹stanbul, Turkey
Phone: (0212) 225 52 15 • Fax: (0212) 225 23 22 e-mail: editor@perinataljournal.com
www.perinataljournal.com
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Coverage
The manuscripts should be prepared for one of the following article categories
which are peer-reviewed:
• Original Article
• Case Report
• Technical Note
• Letter to the Editor
In addition, the journal includes article categories which do not require a peer
review process but are prepared by the Editorial Board or consist of invited articles, titled as:
• Editorial
• Opinion
• Review
• Abstracts
• Announcements
• Erratum
Manuscript Evaluation
All submissions to Perinatal Journal must be original, unpublished, and not under
the review of any other publication. This is recorded by the system automatically
with the IP number, the date and time of submission. On behalf of all authors the
corresponding author should state that all authors are responsible for the manuscripts. The name, date, and place of the relevant meeting should be stated if the
submission is a work that was previously presented in a scientific meeting.
Following the initial review, manuscripts which have been accepted for
consideration are reviewed by at least two reviewers. The Editors of the journal
decide to accept or reject the manuscript considering the comments of the
reviewers. They are authorized to reject or revise the manuscript, to suggest
required corrections and changes upon the comments and suggestions of
reviewers, and/or to correct or condense the text by permission of the corresponding author. They have also the right to reject a manuscript after authors’
revision. Author(s) should provide additional relevant data, documents, or information upon the editorial request if necessary.
Ethical Issues
All manuscripts presenting data obtained from studies involving human subjects
must include a statement that the written informed consent of the participants
was obtained and that the study was approved by an institutional ethics board
or an equivalent body. This institutional approval should be submitted with the
manuscript. Authors of case reports must submit the written informed consent
of the subject(s) of the report or of the patient’s legal representatives for the
publication of the manuscript. All studies should be carried out in accordance
with the World Medical Association Declaration of Helsinki, covering the latest
revision date. Patient confidentiality must be protected according to the universally accepted guidelines and rules. Manuscripts reporting the results of experimental studies on animals must include a statement that the study protocol was
approved by the animal ethics committee of the institution and that the study
was conducted in accordance with the internationally accepted guidelines,
including the Universal Declaration of Animal Rights, European Convention for
the Protection of Vertebrate Animals Used for Experimental and Other Scientific
Purposes, Principles of Laboratory Animal Science, and the Handbook for the
Care and Utilization of Laboratory Animals. The authors are strongly requested
to send the approval of the ethics committee together with the manuscript. In
addition, manuscripts on human and animal studies should describe procedures
indicating the steps taken to eliminate pain and suffering.
The authors should also disclose all issues concerning financial relationship,
conflict of interest, and competing interest that may potentially influence the
results of the research or scientific judgment. All financial contributions or sponsorship, financial relations, and areas of conflict of interest should be clearly
explained in the cover letter to the Editor-in-Chief at the time of submission,
with full assurance that any related document will be submitted to the journal
ii
Perinatal Journal
when requested. For the details of journal's "Conflict of Interest Policy" please
read the PDF document which includes "Conflicts of Interest Disclosure
Statement".
Perinatal Journal is committed to upholding the highest standards of publication ethics and observes the following principles of Publication Ethics and
Malpractice Statement which is based on the recommendations and guidelines
for journal editors developed by the Committee on Publication Ethics (COPE),
Council of Science Editors (CSE), World Association of Medical Editors (WAME)
and International Committee of Medical Journal Editors (ICMJE). For the details
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www.perinataljournal.com.
Manuscript Preparation
In addition to the rules listed below, manuscripts to be published in Perinatal
Journal should be in compliance with the Uniform Requirements for
Manuscripts Submitted to Biomedical Journals published by International
Committee of Medical Journal Editors (ICMJE) of which latest version is available
at www.icmje.org.
Authors are requested to ensure that their manuscript follows the appropriate guidelines such as CONSORT for randomized controlled trials, STROBE for
observational studies, STARD for diagnostic accuracy studies, and PRISMA for
systematic reviews and meta-analyses, for the study design and reporting if
applicable.
Authorship and Length of Texts
The author(s) must declare that they were involved in at least 3 of the 5 stages
of the study stated in the “Acknowledgement of Authorship and Transfer of
Copyright Agreement” as “designing the study”, “collecting the data”, “analyzing the data”, “writing the manuscript” and “confirming the accuracy of the
data and the analyses”. Those who do not fulfill this prerequisite should not be
stated as an author.
Original research articles base on clinical or experimental studies. The
main text should not exceed 2500 words (max. 16 pages), and a maximum of
six authors is advisable.
Case reports should illustrate interesting cases including their treatment
options. The main text should not exceed 2000 words (max. 8 pages), and a
maximum of five authors is advisable.
Viewpoint articles: Only by invitation and should be no more than 2000
words long (max. 8 pages).
Review articles: Only by invitation and should be no more than 40005000 words long (max. 20 pages).
Technical notes aims to present a newly diagnostic or therapeutic
method. They should not exceed 2000 words (max. 8 pages) and include a maximum of 10 references.
Letters to the Editor should be no more than 500 words long (max. 2
pages) and include a maximum of 10 references.
Sections in the Manuscripts
Manuscripts should be designed in the following order: title page, abstract,
main text, references, and tables, with each typeset on a separate page:
Page 1 - Title page
Page 2 - Abstract and key words
Page 3 and next - Main text
Next Page - References
Next Page - Table heading and tables (each table should be placed in separate pages)
Next Page - Figure legends and figures (each figure should be placed in
separate pages)
Last Page - Appendices (patient forms, surveys etc.)
Title page
This page should only include the title of the manuscript, which should be carefully chosen to better reflect the contents of the study. No anusual abbreviations
Information for the Authors
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should be used in the title of the manuscript. A short title as running heading
not exceeding 40 characters should be given which is desired to appear on top
part of continuing pages when journal is published.
should not be used. Papers published in only electronic journals or in the
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Abstract page
Abstracts should not contain any abbreviation and references. They should be
prepared under following designs.
Journal titles should be abbreviated according to the Index Medicus. All
authors if six or fewer should be listed; otherwise, the first six and “et al.”
should be written.
— Abstracts of research articles should be max. 250 words and structured in four paragraphs using the following subtitles: Objective, Methods,
Results, and Conclusion. Following the abstract, each abstract page should
include max. 5 key words separated with comma and written in lower cases.
Direct use of references is strongly recommended and the authors may be
asked to provide the first and last pages of certain references. Publication of the
manuscript will be suspended until this request is fulfilled by the author(s).
— Abstracts of case reports should be max. 125 words and structured in
three paragraphs using the following subtitles: Objective, Case, Conclusion.
Following the abstract, each abstract page should include max. 3 key words separated with comma and written in lower cases.
— Abstracts of review articles should be max. 300 words and presented
not structured in one paragraph. Following the abstract, each abstract page
should include max. 5 key words separated with comma and written in lower
cases.
— Abstracts of technical notes should be max. 125 words and structured
in three paragraphs using the following subtitles: Objective, Technique,
Conclusion. Following the abstract, each abstract page should include max. 3
key words separated with comma and written in lower cases.
— Standard journal article: Hammerman C, Bin-Nun A, Kaplan M.
Managing the patent ductus arteriosus in the premature neonate: a new look
at what we thought we knew. Semin Perinatol 2012;36:130-8.
Main text:
The sections in main text are defined according to the manuscript type.
— In research articles, main text should consist of sections titled as
"Introduction, Methods, Results, Discussion and Conclusion". Each title may
have subtitles. The categories of subtitles should be clearly defined.
The Introduction section should include a brief summary of the base of the
work and clearly states the purpose of the study.
The Methods section should contain a detailed description of the material,
the study design and clinical and laboratory tests, and statistical methods used.
A statement regarding the ethical issues should also be given in this section.
The Results section should provide the main findings of the study. Data
should be concisely presented, preferably in tables or graphs.
The Discussion section should mainly rely on the results derived from the
study, with relevant citations from the most recent literature.
The Conclusion section should briefly and claearly present the conclusions
derived from the results of the study. It should be in compliance with the aim of
the work and and point out its application in clinical practice.
— In Case Reports, main text should be divided with the titles
"Introduction, Case(s), Discussion". Reported case(s) should be introduced
clearly including the case story, and the results of laboratory tests should be
given in table format as far as possible.
— The text of the reviews articles should follow the "Introduction" and
be organized under subtitles which should clearly define the text's context categorization. The Reviews are expected to include wide surveying of literature
and reflect the author's personal experiences as far as possible.
— The text of the technical note type of articles should be divided into
"Introduction, Technic, Discussion". The presented technic should be defined
briefly under the related title, and include illustrations or figures as soon as possible.
— Letters to the Editor should not have titled sections. If there is a citation about a formerly published article within the text, reference(s) should be
provided.
References
References used in the text should be directly related to the topic, as recent as
possible and in enough numbers. They should be numbered in square brackets
in the order in which they are mentioned in the text including Tables and
Figures. Citation order should be checked carefully.
Only published articles or articles in press can be used in references.
Unpublished data including conference papers or personal communications
The style and punctuation should follow the formats outlined below:
— Article published in an only electronic journal: Lee J, Romero R, Xu
Y, Kim JS, Topping V, Yoo W, et al. A signature of maternal anti-fetal rejection
in spontaneous preterm birth: chronic chorioamnionitis, anti-human leukocyte
antigen antibodies, and C4d. PLoS ONE 2011;6:e16806. doi:10.1371/
journal.pone.0011846.
— Book: Jones KL. Practical perinatology. New York: Springer; 1990. p.
112-9.
— Chapter in a book: Sibai BM, Frangieh AY. Eclampsia. In: Gleicher N,
editors. Principles and practice of medical therapy in pregnancy. 3rd ed. New
York: Appleton&Lange; 1998. p. 1022-7.
Figures and tables
All illustrations (photographs, graphics, and drawings) accompanying the manuscript should be referred to as “figure”. All figures should be numbered consecutively and mentioned in the text. Figure legends should be added at the end
of the text as a separate section. Each figure should be prepared as a separate
digital file in “jpeg” format, with a minimum 300 dpi or better resolution. All
illustrations should be original. Illustrations published elsewhere should be submitted with the written permission of the original copyright holder. For recognizable photographs of human subjects, written permission signed by the
patient or his/her legal representative should be submitted; otherwise, patient
names or eyes must be blocked out to prevent identification. Microscopic photographs should include information on staining and magnification.
Each table should be prepared on a separate page with table heading on
top of the table. Table heading should be added to the main text file on a separate page when a table is submitted as a supplementary file.
Submission
For a swift peer review, Perinatal Journal operates a web-based submission, peer
review and manuscript tracking system. Authors are required to submit their
articles online. Details of how to submit online can be found at www.perinataljournal.com.
Submission Checklist
The following list will be useful during the final check of a manuscript before
submission:
1. Manuscript length (max. 4000 words for research articles)
2. Number of authors (max. 6 authors for research articles)
3. Title page (no anusual abbreviations)
4. Abstracts (max. 250 words for research articles)
5. Key words (max. 5 keys for research articles)
6. Main text (subtitles)
7. References (listed according to the rules of ICMJE)
8. Figures and tables (numbering; legends and headings; copyright
info/permission)
9. Cover letter
10. Acknowledgement of Authorship and Transfer of Copyright
Agreement (undersigned by all authors)
11. Conflicts of Interest Disclosure Statement (if necessary)
Volume 23 | Issue 1 | April 2015
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Contents
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Original Articles
Ultrasonographic evaluation of ventriculomegaly cases
1
Hakan Kalayc›, Halis Özdemir, Ça¤r› Gülümser, Ayfle Parlakgümüfl, Tayfun Çok, Ebru Tar›m, Filiz Bilgin Yan›k
Perinatal outcomes of patients diagnosed borderline gestational diabetes mellitus
6
Gök Özgül, Rauf Meleko¤lu, Sevda Yeleç, ‹pek Eskiyörük, Fatma Tuncay Özgünen
Health practices of pregnant women in Gumushane City Center
13
Handan Özcan, Nezihe K›z›lkaya Beji
The evaluation of pregnancies complicated by eclampsia: retrospective analysis of 37 cases in our clinic
20
Aytekin Tokmak, Korkut Da¤lar, Ali ‹rfan Güzel, Bergen Laleli, Salim Erkaya, Dilek Uygur
Factors affecting postpartum depression in Diyarbak›r
26
Ali Emre Tahao¤lu, Cihan To¤rul, Mehmet ‹rfan Külahç›o¤lu, Beflire Ayd›n Öztürk, Deniz Balsak,
Hanifi Bademk›ran, Erdo¤an Gül, Ümit Görkem, Tayfun Güngör
Analysis of maternal serum and urinary lipocalin-2 levels
30
Yeflim Bayo¤lu Tekin, Ülkü Mete Ural, Aynur K›rbafl, fienol fientürk, Figen K›r fiahin
Critical pulmonary stenosis with prenatal diagnosis: a case series and review of literature
34
Oya Demirci, Taner Yavuz, Resul Ar›soy, Emre Erdo¤du, P›nar Kumru, Oya Pekin
Evaluation of prenatal invasive procedures: analysis of retrospective cases
39
Aybike Tazegül Pekin, Özlem Seçilmifl Kerimo¤lu, Setenay Arzu Y›lmaz, Nadir Koçak,
Feyza Nur ‹ncesu, Ayfle Gül Kebapc›lar, Çetin Çelik
Investigation of the effects of fetal gender on umbilical artery and middle cerebral artery Doppler findings
45
Burcu Artunç Ülkümen, Halil Gürsoy Pala, Y›ld›z Uyar, Yeflim Baytur, Faik Mümtaz Koyuncu
Results of routine first trimester screening tests and following invasive procedures during pregnancy
50
Rahime Nida Ergin, Murat Yayla
Case Reports
The association of congenital hand reduction defect and uterine anomaly
56
Bülent Kars, Önder Sakin, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak
Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case
60
Sevil Eraslan, Rauf Meleko¤lu, Ebru Çelik
Goiter in fetus without maternal thyroid disease: a case report
65
Önder Sakin, Bülent Kars, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak
Letter to Editor
Letter to the Editor regarding “Extrauterine intrapartum treatment procedure in the unilateral
advanced fetal hydrothorax case”
Baflak Kaya, Ali Gedikbafl›
iv
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Ultrasonographic evaluation of
ventriculomegaly cases
Hakan Kalayc›, Halis Özdemir, Ça¤r› Gülümser, Ayfle Parlakgümüfl, Tayfun Çok, Ebru Tar›m, Filiz Bilgin Yan›k
Department of Gynecology & Obstetrics, Medical School of Baflkent University, Ankara, Turkey
Abstract
Özet: Ventrikülomegali vakalar›n›n ultrasonografik
de¤erlendirilmesi
Objective: To evaluate retrospectively the demographic data of the
patients diagnosed in or referred with the pre-diagnosis of ventriculomegaly to Perinatology Department of Adana and Ankara
Hospitals of Baflkent University.
Methods: In this study, 61 pregnant women with fetal ventriculomegaly diagnosed in our clinic or referred by other centers to the
Perinatology Department of Ankara and Adana Hospitals of
Baflkent University between May 2008 and March 2013 were evaluated in terms of their demographic data, diagnosis weeks, concomitant anomalies and the course of their pregnancies. SPSS v.
16.0 was used for statistical calculations.
Results: The analysis of 61 pregnant women between 20 and 41
years old showed that it was the first pregnancy of 45.9% of them.
Only 16.4% of them were at or over 35 years old. It was observed that
4.9% of them were conceived by assisted reproduction techniques.
The rates of mild (10–12 mm), moderate (12.1–14.9 mm) and severe
ventriculomegaly (≥15 mm) were 65.6%, 24.7% and 4.8%, respectively. Toxoplasma, Cytomegalovirus, Rubella or Herpes virus infections were not found in any case. Down syndrome was found in the
karyotype analysis of 3 patients (4.9%). The ventriculomegaly was
unilateral in 67.2% of the cases. The detection rate between 16 and
24 weeks which were also the weeks for detailed ultrasonography was
52.5%. There was an additional anomaly in 33.3% of the cases. The
most frequent concomitant anomalies were found as increased nuchal
thickness (13.3%), corpus callosum agenesis (11.1%) and nasal bone
hypoplasia (8.9%). In their follow-ups, it was observed that the findings were regressed in 53.8% of the cases, progressed in 19.3% of the
cases and remained unchanged in 26.9%.
Conclusion: When ventriculomegaly is detected, the presence of
additional anomalies should be investigated by detailed ultrasonographic examination during etiological investigation. In the selective
cases, the physicians may utilize the method of magnetic resonance
imaging to evaluate additional cerebral anomalies. It is also necessary
to recommend karyotype analysis and investigating Toxoplasma,
Rubella, Cytomegalovirus and Herpes virus infections in the presence of additional anomaly and even in isolated cases regardless of the
level of ventriculomegaly. Patients should be followed up regularly.
Amaç: Baflkent Üniversitesi Adana ve Ankara Hastaneleri Perinatoloji bilim dal›nda tan› alm›fl veya ventrikülomegali ön tan›s› ile
refere edilmifl hastalar›n demografik verilerinin retrospektif olarak
de¤erlendirilmesi.
Yöntem: Bu çal›flmada May›s 2008 ve Mart 2013 tarihleri aras›nda Baflkent Üniversitesi Ankara ve Adana Hastaneleri Perinatoloji
Bilim Dal›na d›flar›dan gönderilen veya klini¤imizde tespit edilen
fetal ventrikülomegalisi olan 61 gebe demografik verileri, tan› konulma haftalar›, efllik eden anomaliler ve gebeliklerin seyri aç›s›ndan de¤erlendirildi. ‹statistiksel hesaplamalarda SPSS v. 16.0’dan
faydalan›ld›.
Bulgular: 20–41 yafl aras› 61 gebenin de¤erlendirmesinde,
%45.9’unun ilk gebelikleriydi. %16.4’ü 35 yafl ve üzeriydi.
%4.9’unun yard›mc› üreme teknikleri ile gebe kald›¤› izlendi. Hafif (10–12 mm), ›l›ml› (12.1–14.9 mm) ve ciddi ventrikülomegali
(≥15 mm) oranlar› s›ras› ile %65.6, %24.7 ve %4.8 idi. Hiçbir vakada toksoplazma, sitomegalovirüs, rubella veya Herpes virüs enfeksiyonu saptanmad›. Karyotip analizinde 3 hastada Down sendromu tespit edildi (%4.9). Ventrikülomegalilerin %67.2’si tek tarafl› idi. Ayr›nt›l› ultrasonografi haftas› olan 16–24 haftalar› aras›
tespit oran› %52.5 idi. %33.3 ek anomali mevcuttu. En s›k efllik
eden anomaliler s›kl›k s›ras›na göre artm›fl nukal kal›nl›k (%13.3),
korpus kallozum agenezisi (%11.1) ve nazal kemik hipoplazisi
(%8.9) olarak izlendi. Takiplerde %53.8 vakada bulgular›n geriledi¤i, %19.3’ünde ilerledi¤i ve %26.9’unda de¤iflmeden kald›¤› izlendi.
Sonuç: Ventrikülomegali tespit edildi¤inde etyoloji araflt›rmas›nda ayr›nt›l› ultrasonografik muayene ile ek anomalilerin varl›¤›
araflt›r›lmal›d›r. Selektif vakalarda ek serebral anomalileri de¤erlendirmek için manyetik rezonans görüntüleme yönteminden faydalan›labilir. Karyotip analizi ve toksoplazma, rubella, sitomegalovirüs ve Herpes virüs enfeksiyonlar›n›n araflt›r›lmas› ek anomali
varl›¤›nda ve hatta izole vakalarda ventrikülomegalinin derecesi ne
olursa olsun önerilmelidir. Hastalar düzenli takibe al›nmal›d›r.
Keywords: Isolated ventriculomegaly, additional anomalies, followup.
Anahtar sözcükler: ‹zole ventrikülomegali, ek anomaliler, takip.
Correspondence: Hakan Kalayc›, MD. Baflkent Üniversitesi T›p Fakültesi Kad›n
Hastal›klar› ve Do¤um Anabilim Dal›, Ankara, Turkey. e-mail: smartdr96@yahoo.com
Received: April 15, 2014; Accepted: September 7, 2014
Please cite this article as: Kalayc› H, Özdemir H, Gülümser Ç, Parlakgümüfl A, Çok T,
Tar›m E, Bilgin Yan›k F. Ultrasonographic evaluation of ventriculomegaly cases.
Perinatal Journal 2015;23(1):1–5.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231001
doi:10.2399/prn.15.0231001
QR (Quick Response) Code:
Kalayc› H et al.
Introduction
The term ventriculomegaly (VM) is used for the cases
where anterior horns of ventricle, cavum septum pellucidum and choroid plexus can be seen in the axial plane
and lateral ventricle measurement on the plane is 10
mm and above at the glomus level of choroid plexus
(Fig. 1).[1,2] There are various definitions according to
the width of lateral ventricle. When lateral ventricle
measurements are 10–12 mm and 12.1–15 mm, the
definitions of mild and moderate VM are used.[3,4]
However, some authors deny 10-12 mm as mild VM
and define mild VM as 10-15 mm.[5] In measurements
which are 15 mm and above, severe VM term is used.[6]
While mild VM prevalence is 7.9 out of 10,000 live
births, severe VM prevalence is reported as 3.6 out of
10,000 live births.[7]
Many factors are assumed in the etiology such as
infections; cerebral atrophy induced by white matter
injury and/or cases causing absorption of cerebrospinal
fluid to decrease; obstructive causes such as DandyWalker malformation or aqueductal stenosis; developmental anomalies such as encephalocele, corpus callosum agenesis (Figs. 2a and 2b); genetic disorders such
as trisomy 13, 18 and 21; and cases such as choroid
plexus papilloma which may cause excessive cerebrospinal fluid production.[8] This expansion in ventricles may be accompanied by anomalies such as hydrocephaly, gray matter migration anomalies, corpus callosum agenesis, trisomies and microcephaly.[5] The
incidence of associated cerebral or extracerebral anomalies varies between 41% and 78%.[2] Many authors
a
Fig. 2.
2
Fig. 1.
Moderate ventriculomegaly.
believe that the presence of additional malformations is
directly associated with the prognosis. Prognosis is
observed better in most of the isolated VM cases.[2,9]
Therefore, prenatal diagnosis becomes crucial.
In this study, we aimed to analyze the demographic
data, diagnosis weeks, concomitant anomalies and the
course of pregnancy retrospectively in patients diagnosed with ventriculomegaly during intrauterine period.
Methods
In this study, 61 pregnant women with fetal ventriculomegaly diagnosed in our clinic or referred by other
centers to the Perinatology Department of Ankara and
b
(a) Corpus callosum agenesis (arrow). (b) Corpus callosum agenesis, colpocephaly, teardrop appearance (arrow).
Perinatal Journal
Ultrasonographic evaluation of ventriculomegaly cases
Adana Hospitals of Baflkent University between May
2008 and March 2013 were evaluated in terms of their
demographic data, diagnosis weeks, concomitant
anomalies and the course of their pregnancies. All
fetuses were evaluated by detailed fetal biometric
examination. Statistical data were analyzed by SPSS v.
16.0 (SPSS Inc., Chicago, IL, USA) software.
Results
The analysis of 61 pregnant women between 20 and 41
years old showed that it was the first pregnancy of
45.9% of them. Only 16.4% of them were at or over 35
years old. It was observed that 4.9% of them were conceived by assisted reproduction techniques. The rates
of mild (10–12 mm), moderate (12.1–14.9 mm) and
severe ventriculomegaly (≥15 mm) were 65.6%, 24.7%
and 4.8%, respectively. No Toxoplasma, Rubella,
Cytomegalovirus (CMV) and Herpes virus infection
was found in any of the pregnant women. Down syndrome was found in the karyotype analysis of 3 fetuses
(4.9%). The ventriculomegaly was unilateral in 67.2%
of the cases. The detection rate between 16 and 24
weeks which were also the weeks for detailed ultrasonography was 52.5%. The most frequent concomitant anomalies were observed as increased nuchal
thickness (13.3%), corpus callosum agenesis (11.1%),
and nasal bone hypoplasia (8.9%). Additionally, obstetric magnetic resonance was applied to 44.3% of the
pregnant women. Of pregnant women, 72.5% of them
delivered at 37 weeks or later. In their follow-ups, it
was observed that the findings were regressed in 53.8%
of the cases, progressed in 19.3% of the cases and
remained unchanged in 26.9%.
Discussion
In the detailed ultrasonographic examination performed on 18–22 weeks of gestation, it is routinely recommended to measure the width of lateral cerebral
ventricles.[1,10,11] In the lateral ventricle measurements,
10–12 mm is defined as mild VM, 12.1–15 mm as moderate and 15 mm, and above as severe VM.[3,4]
Infections may also have a role in the etiology. In
the study of Do¤an et al., severe VM was found in 5 of
8 cases with CMV infection, increased periventricular
echogenicity, intracranial calcification in 4 cases, thalamic hyperechogenicity in 3 cases, and mega cisterna
magna.[12] Tijana et al. found VM, which did not display
any finding on previous weeks, in patient with positive
toxoplasmosis at 25 weeks of gestation.[13] Dommergues
et al. detected CMV positivity in 29% of the cases in
their study.[14] In various publications, infection positivity was observed as 10–20% in severe VM cases while
it was 1–5% in mild VM cases.[9,15,16] Therefore, it is recommended to evaluate all cases diagnosed with VM in
terms of infection.[6,15,17,18] In our study, no infection factor was found; the reason is the rate of severe VM seen
in our patients as low as 4.8%.
Chromosomal anomaly incidence varies in VM
cases between 0% and 14%.[5,6,15] In our study, Down
syndrome was found in 4.9% (3) cases. While
Nicolaides et al. reported chromosomal anomaly incidence as 3% in isolated VM cases, they showed this
rate as 36% in the presence of additional anomaly.
Also, aneuploidy was reported at a low rate in isolated
severe VM cases compared to isolated mild VM
cases.[19] Similarly, Melchiorre et al. reported the rate of
chromosomal anomaly in isolated cases as 2.8%.[20]
Gaglioti et al. did not find any chromosomal anomaly
in severe VM cases while aneuploidy rate was 3.5% in
mild and moderate VM cases.[16] Gezer et al. reported
chromosomal anomaly incidence (6.8%) in fetuses with
severe ventriculomegaly higher than the fetuses with
mild ventriculomegaly (4.2%). Chromosomal anomaly
incidence (8.6%) in fetuses with isolated ventriculomegaly was also found higher than those with additional anomaly (3.8%).[21] Sezik observed Type 2
triploidy case with VM accompanied by atrioventricular septal defect.[22] Kara described the association of
VM and 47 XXY syndrome in a case report.[23]
In ventriculomegaly cases, it is possible to observe
both cerebral and extracerebral malformations as an
additional anomaly. They especially accompany with
severe VM. The most frequent concomitant anomalies
of severe VM cases are corpus callosum agenesis and
bifid spine.[24,25] In mild and moderate VM cases, this
rate varies between 10% and 76%.[17,26] Various studies
reported additional anomaly incidence at rates reaching up to 50%.[6,11,15] Gaglioti et al. found additional
anomaly in 60% of severe VM cases. In 88% of these
cases, families preferred to terminate the pregnancy.[16]
Tatl› et al. found additional anomaly in 9% of cases
with 10-15 mm ventricle width.[27] In our study, the
most frequent additional anomalies (33.3%) were
increased nuchal thickness (13.3%), corpus callosum
agenesis (11.1%) and nasal bone hypoplasia (8.9%).
Volume 23 | Issue 1 | April 2015
3
Kalayc› H et al.
We observed in our study that the findings were
regressed in 53.8% of the cases, progressed in 19.3%
of the cases and remained unchanged in 26.9%.
Ouahba et al. reported regression in 11% of 167 mild
VM cases, and they observed more regression in these
cases in terms of neurological development.[9]
Melchiorre et al. found a progression at a rate of
15.7%. In those with progression, there was poor
prognosis in terms of neurological development and
association with chromosomal anomalies.[20]
During magnetic resonance imaging, Levine et al.
found additional findings at a rate of 13.5% which may
change patient management in cases found to have
anomaly by ultrasonography.[28] Gezer et al. asserted that
ventricle width and brain parenchyma volume rate may
be helpful to determine prognosis in magnetic resonance imaging. Parenchyma volumes of those with poor
prognosis were found to be low.[29] We applied obstetric
magnetic resonance imaging to 44.3% of our cases. We
confirmed the diagnosis of corpus callosum agenesis in
four fetuses by ultrasonography, cortical atrophy in one
case, and encephalomalacia in one case. In line with
these findings, magnetic resonance imaging is significant to confirm the suspected diagnoses established by
ultrasonography. The use of magnetic resonance imaging is useful for pathologies such as neuronal migration
disorders, delayed sulcation, gyrus formation and heterotopias which can be detected at late second and third
trimesters and overlooked by ultrasonography.[30,31]
After the 11 years of follow-up of 101 children with
isolated VM, normal psychomotor development was
observed in 89 of them, and neurological disorder in
the spectrum reaching out from language delay up to
the severe mental retardation.[12]
Vergani et al. found neurological development retardation clearly lower in groups with 12 mm and lower
widths than the group with 12 mm and above (3% vs.
23%).[6] Devaseelan et al. reported neurological development retardation as 14% in children with progressed
VM during intrauterine period.[32] In another study,
scores below the normal levels were reported for fine
motor skills and language development in children with
persisting ventricle width during prenatal period.[33]
Conclusion
When ventriculomegaly is detected, the presence of
additional anomalies should be investigated by detailed
4
Perinatal Journal
ultrasonographic examination during etiological investigation. In the selected cases, the physicians may utilize the method of magnetic resonance imaging to
evaluate additional cerebral anomalies. In line with the
current information we have, we recommend performing karyotype analysis and investigating Toxoplasma,
CMV and infections such as Rubella regardless of the
level of ventriculomegaly and even in the isolated ventriculomegaly cases without any additional anomaly.
Patients should be followed up regularly. The parents
should be informed in detail for the neuropsychiatric
conditions that may arise during postpartum period.
Conflicts of Interest: No conflicts declared.
References
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13. Zivkoviç T, Ivoviç V, Vujaniç M, Klun I, Bobiç B, Nikoliç A,
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14. Dommergues M, Mahieu-Caputo D, Fallet-Bianco C,
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15. Pilu G, Falco P, Gabrielli S, Perolo A, Sandri F, Bovicelli L.
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16. Gaglioti P, Danelon D, Bontempo S, Mombrò M,
Cardaropoli S, Todros T, et al. Fetal cerebral ventriculomegaly: outcome in 176 cases. Ultrasound Obstet Gynecol
2005;25:372–7.
17. den Hollander NS, Vinkesteijn A, Schmitz-van Splunder P,
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18. Pilu G, Hobbins JC. Sonography of fetal cerebrospinal anomalies. Prenat Diagn 2002;22:321–30.
19. Nicolaides KH, Berry S, Snijders RJM, Thorpe-Beeston JG,
Gosden C. Fetal lateral cerebral ventriculomegaly: associated malformations and chromosomal defects. Fetal Diagn
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20. Melchiorre K, Bhide A, Gika AD, Pilu G, Papageorghiou
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al. Fetal serebral ventikülomegalide kromozomal anomali
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24. Breeze ACG, Alexander PMA, Murdoch EM, MissfelderLobos HH, Hackett GA, Lees CC. Obstetric and neonatal
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124–9.
25. Morris JE, Rickard S, Paley MNJ, Griffiths PD, Rigby A,
Whitby EH. The value of in-utero magnetic resonance
imaging in ultrasound diagnosed foetal isolated cerebral venticulomegaly. Clin Radiol 2007;62:140–4.
26. Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JC. The
central nervous system. Prenatal Diagnosis of Congenital
Anomalies. East Norwalk, CT: Appleton & Lange; 1988. p.
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27. Tatl› B, Özer I, Ekici B, Kalelio¤lu I, Has R, Eraslan E, et al.
Neurodevelopmental outcome of 31 patients with borderline
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114;969–71.
28. Levine D, Barnes PD, Robertson RR, Wong G, Mehta T.
Fast MR imaging of fetal central nervous system abnormalities. Radiology 2003;229:51–61.
29. Gezer NS, Güleryüz H, Gezer C, Koçyi¤it A, Yeflil›rmak
CD, Güçlü S, et al. Fetal manyetik rezonans görüntüleme ile
yap›lan beyin hacim ölçümlerinin ventrikülomegali ile
iliflkisi. Perinatoloji Dergisi 2013;21 Suppl 1:S35.
30. Benaceraf BR, Shipp TD, Bromley B, Levine D. What does
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1513–22.
31. Manganaro L, Savelli S, Francioso A, Di Maurizio M,
Coratella F, Vilella G, et al. Role of fetal MRI in the diagnosis of cerebral ventriculomegaly assessed by ultrasonography.
Radiol Med 2009;114:1013–23.
32. Devaseelan P, Cardwell C, Bell B, Ong S. Prognosis of isolated mild to moderate fetal cerebral ventriculomegaly: a systematic review. J Perinat Med 2010;38:401–9.
33. Lyall AE, Woolson S, Wolfe HM, Goldman BD, Reznick
JS, Hamer RM, et al. Prenatal isolated mild ventriculomegaly is associated with persistent ventricle enlargement
at ages 1 and 2. Early Hum Dev 2012;88;691–8.
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Original Article
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Perinatal outcomes of patients diagnosed borderline
gestational diabetes mellitus
Gök Özgül1, Rauf Meleko¤lu2, Sevda Yeleç1, ‹pek Eskiyörük1, Fatma Tuncay Özgünen1
1
Department of Gynecology & Obstetrics, Faculty of Medicine, Çukurova University, Adana, Turkey
2
Department of Gynecology & Obstetrics, Faculty of Medicine, Inönü University, Malatya, Turkey
Abstract
Özet: Borderline gestasyonel diabetes mellitus
saptanan gebelerin perinatal sonuçlar›
Objective: Although the effects of gestational diabetes mellitus to
maternal and fetal health are well known, we have few data about
maternal and fetal condition of borderline gestational diabetic pregnants who have gestational hyperglycemia not meeting gestational
diabetes criteria. Considering this, we aimed to investigate perinatal
and neonatal outcomes of patients who have borderline gestational
diabetes mellitus in our hospital.
Methods: In this study, we retrospectively examined maternal characteristics, obstetric and perinatal outcomes of pregnants whose
antenatal follow-up and birth occurred in Department of Obstetrics
and Gynecology in Faculty of Medicine in Çukurova University
between January 2009 and January 2013 and who have normal 50g oral glucose tolerance test (OGTT) but abnormal 100-g OGTT
and have normal 50-g OGCT test results. SPSS v. 19.0 statistics
software was used for data analysis. For the statistical significance
level between results, p value was taken as <0.05.
Results: A total of 239 pregnant women were included in the study.
The study group consisted of 105 pregnant women whose 50-g
OGTT results were abnormal but 100-g OGTT results were within
normal limits and the control group consisted of 134 pregnant
women whose 50-g OGTT results were within normal limits.
Compared to healthy pregnant women, mean age of the women in
the study group was found to be significantly higher (p=0.000). The
duration of hospitalization in the study group was found to be statistically significantly higher compared to the control group (p=0.001).
Mode of delivery, preterm labor, premature rupture of membranes,
gestational hypertension, preeclampsia, the presence of fetal distress
and postpartum hemorrhage were analyzed in both groups. Only
postpartum hemorrhage was found to be statistically significantly
higher in the study group compared to the control group (p=0.049).
There was statistically no significant difference in neonates between
two groups for LGA, SGA, hypoglycemia, hyperbilirubinemia,
neonatal admissions to the intensive care unit and neonatal death.
Conclusion: In our study, perinatal and neonatal outcomes of
patients who have borderline gestational diabetes mellitus and normoglisemic condition are same except postpartum hemorrhage and
hospitalization period. To acquire perinatal and neonatal outcomes
of women with borderline gestational diabetes mellitus, we need further well-designed randomized studies with larger populations.
Amaç: Çal›flman›n amac› gestasyonel diyabetin fetal ve maternal
sa¤l›¤a etkileri oldukça iyi bilinmesine ra¤men, gestasyonel diyabet kriterlerini karfl›lamayan gebelik hiperglisemisine sahip borderline gestasyonel diyabeti olan gebelerin maternal ve fetal durumunu ortaya koyan az say›da çal›flma olmas›n› göz önünde bulundurarak, hastanemizdeki borderline gestasyonel diyabeti olan hastalar›n perinatal ve neonatal sonuçlar›n› irdelemektir.
Yöntem: Bu çal›flmada Ocak 2009 ve Ocak 2013 tarihleri aras›nda
Çukurova Üniversitesi T›p Fakültesi Kad›n Hastal›klar› ve Do¤um Anabilim Dal› Gebe Poliklini¤inde antenatal izlemleri yap›lan ve do¤umlar› klini¤imizde gerçekleflen gebeler aras›ndan 50 g
OGTT sonuçlar› yüksek ancak 100 g OGTT sonuçlar› normal
olan hastalar ile 50 g OGTT sonuçlar› normal olan hastalar tespit
edilerek, maternal özellikleri, obstetrik ve perinatal sonuçlar› retrospektif olarak incelendi. Verilerin analizi için SPSS v 19.0 paket
program› kullan›ld›. Sonuçlar aras›nda istatistiksel anlaml›l›k düzeyi için p de¤eri <0.05 olarak al›nd›.
Bulgular: Çal›flmaya toplamda 239 gebe dahil edildi. 50 g OGTT
sonuçlar› yüksek ancak 100 g OGTT sonuçlar› normal s›n›rlarda
olan 105 gebe çal›flma grubunu, 50 g OGTT sonuçlar› normal
olan 134 gebe ise kontrol grubunu oluflturdu. Çal›flma grubundaki gebelerin yafl ortalamalar›n›n sa¤l›kl› gebelere oranla istatistiksel olarak anlaml› derecede yüksek oldu¤u saptand› (p=0.000). Çal›flma grubundaki gebelerin hastanede yat›fl sürelerinin kontrol
grubundakilere oranla istatistiksel olarak anlaml› oranda daha fazla oldu¤u saptand› (p=0.001). Her iki grubun do¤um flekli, erken
do¤um, erken membran rüptürü, gestasyonel hipertansiyon, preeklampsi varl›¤›, fetal distres varl›¤› ve postpartum kanama aç›s›ndan obstetrik sonuçlar› incelendi. Sadece postpartum kanaman›n
kontrol grubuna göre çal›flma grubunda istatistiksel olarak anlaml› derecede fazla oldu¤u saptand› (p=0.049). Yenido¤an bebeklerde
LGA, SGA, hipoglisemi, hiperbilirubinemi, yenido¤an yo¤un bak›m ünitesine yat›fl ve neonatal ölüm görülme oranlar› aras›nda da
her iki grup aras›nda istatistiksel olarak anlaml› fark saptanmad›.
Sonuç: Çal›flmam›zda borderline gestasyonel diyabeti olan hastalar›n postpartum kanama s›kl›¤› ve hastanede yat›fl süreleri d›fl›nda
perinatal ve neonatal sonuçlar› normoglisemik gebeler ile benzer
saptanm›flt›r.
Keywords: Gestational diabetes, glucose tolerance test, pregnancy
outcomes.
Anahtar sözcükler: Gestasyonel diyabet, glukoz tolerans testi,
gebelik sonuçlar›.
Correspondence: Rauf Meleko¤lu, MD. ‹nönü Üniversitesi T›p Fakültesi Kad›n
Hastal›klar› ve Do¤um Anabilim Dal›, Malatya, Turkey. e-mail: rmelekoglu@gmail.com
Received: November 17, 2014; Accepted: November 30, 2014
Please cite this article as: Özgül G, Meleko¤lu R, Yeleç S, Eskiyörük ‹,
Tuncay Özgünen F. Perinatal outcomes of patients diagnosed borderline gestational
diabetes mellitus. Perinatal Journal 2015;23(1):6–12.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231002
doi:10.2399/prn.15.0231002
QR (Quick Response) Code:
Perinatal outcomes of patients diagnosed borderline gestational diabetes
Introduction
Gestational diabetes mellitus (GDM) is defined as the
“carbohydrate intolerance occurring or found for the
first time during pregnancy”.[1] Pregnancy is characterized by insulin resistance and hyperinsulinemia. This
may be predisposing for pregnant women to develop
diabetes. This resistance is caused by the influence of
some diabetogenic placental secretion hormones
(growth hormone, corticotropin releasing hormone, placental lactogenic hormone, progesterone etc).
Decreased exercise, increased caloric intake and
increased adiposis tissue amount are also among the reasons of insulin resistance. Gestational diabetes is seen in
women who have insufficient pancreatic functions and
do not have insulin release sufficient enough to tolerate
diabetogenic hormone change.[2]
It is recommended to all pregnant women to have
50-g oral glucose tolerance test (OGTT) for gestational
diabetic screening between 24 and 28 weeks of gestation.[3] If the result is above 140 mg/dl, patient is referred
to 100-g OGTT. For GDM diagnosis, at least two
threshold values of 100-g OGTT should be met or
exceeded. However, there is also a major patient group
who has positive result for 50-g OGTT but normal
result for 100-g OGTT. Although the effects of gestational diabetes mellitus to maternal and fetal health are
well known, maternal and fetal conditions of borderline
gestational diabetic women who are between normal
glucose values and gestational diabetic levels. Some
studies in the literature point out that the pregnant
women with normal 100-g OGTT results despite high
50-g OGTT results may have different maternal characteristics compared to normal pregnant women and
may have more risks in terms of adverse obstetric outcomes.[4] This group is called as “borderline GDM”.
In our study, we aimed to analyze retrospectively the
pregnant women with normal 100-g OGTT results
despite high 50-g OGTT results and the pregnant
women with normal 50-g OGTT results among the cases
who were followed up and delivered at the Department
of Gynecology & Obstetrics, Faculty of Medicine,
Çukurova University between January 2009 and January
2013, and to investigate and compare their maternal
characteristics and obstetric and perinatal outcomes.
Methods
This study includes 239 pregnant women who had
their antenatal follow-ups and deliveries at the
Department of Gynecology & Obstetrics, Faculty of
Medicine, Çukurova University between January 2009
and January 2013 in accordance with the follow-up and
delivery protocols prepared in compliance with the
Prenatal Care Management Guide and Delivery and
Cesarean Labor Management Guide of the Health
Ministry, and their babies.
The approval of the Ethics Committee of Faculty
of Medicine, Çukurova University was obtained before
the study. Also, in compliance with the Helsinki
Declaration Principles, all women included in the
study were informed in written and verbally about the
study and their informed consents were received.
The study group consisted of 105 pregnant women
who were at 24-28 weeks of gestation, undergone GDM
screening and had normal results for 100-g OGTT
despite the high results for 50-g OGTT (those having
all values below the threshold value of 100-g OGTT
and those with single high value), and the control group
consisted of 134 pregnant women who delivered at the
same period and had normal results for 50-g glucose
screening test performed at 24-28 weeks of gestation.
Pregnant women below 18-year-old and above 35year-old, multipara pregnant women, those with multiple pregnancies, presence of major fetal anomaly in
fetus and of maternal chronic diseases (such as chronic
hypertension, diabetes mellitus, chronic renal failure
asthma, pulmonary or cardiac diseases etc.), patients
with maternal thrombophilia history and pregnant
women who undergone labor induction were excluded
from the study.
In our clinic, we perform 50-g OGTT to pregnant
women, who admit to follow-up clinics between 24 and
28 weeks of gestation, by orally administering 50 g glucose dissolved in 200 ml water. One hour after patient
receives glucose solution, venous blood sample is collected from patient and plasma glucose levels are measured spectrophotometrically via oxidase method by
using Roche diagnostic kits on Roche/Hitachi (Roche
Diagnostics Corp., Indianapolis, IN, USA) device in
biochemistry laboratory.
Those with blood glucose levels:
• Below 140 mg/dl are considered as normal
• Above 200 mg/dL are considered as directly GDM
• For those with a value between >140 mg and <200
mg, OGTT is carried out with 100 g glucose after
8-14 of fasting. During this test, venous blood samVolume 23 | Issue 1 | April 2015
7
Özgül G et al.
ple is collected from patient for fasting blood glucose first and after 100 g glucose dissolved in 200
ml is administered to patient, venous blood samples
are collected first, second, and third hours, and the
samples are analyzed in biochemistry laboratory.
GDM diagnosis is established when at least two
threshold values used by National Diabetes Data
Group are met or exceeded (fasting: 105, first hour:
190, second hour: 165, third hour: 145).
The patients who were included in the study were
retrospectively recorded and compared in terms of
demographical data such as age, weight, body mass
index, smoking habit, gestational age, blood pressure
data during the referral for delivery; perinatal data such
as preterm labor as a perinatal outcome (delivery before
37+0 weeks of gestation), pregnancy induced hypertension (hypertension developed without proteinuria after
20 weeks of gestation), presence of preeclampsia (hypertension developed with proteinuria after 20 weeks of
gestation), delivery type (vaginal delivery/cesarean),
presence of cesarean, shoulder dystocia and postpartum
hemorrhage due to fetal distress (≥500 ml blood loss
through genital tract after delivery), hospitalization period; and neonatal data such as APGAR score, head circumference, gender, LGA rates according to gestational
age [birth weight being ≥90 p according to gestational
age], SGA rates according to gestational age [birth
weight being ≤10 p according to gestational age], neonatal hypoglycemia (blood glucose below 40 mg/dl regardless of birth weight and gestational week), nenonatal
hyperbilirubinemia (blood bilirubin levels being at
pathological levels according to gestational age, weight
and gender), newborn intense care need and neonatal
mortality rates of babies born in both groups.
SPSS ver. 19.0 software was used for the statistical
analysis of the data. Categorical measurements were
summarized as figures and percentages while constant
measurements were indicated as mean and standard
deviation. The distributions were checked in the comparison of constant measurements among groups; t-test
for two independent samples was used for variables displaying parametric distribution while Mann-Whitney U
test was used for variables not displaying parametric distribution. Either chi-square test or Fisher’s test statistics
was used for the comparison of categorical variables
such as smoking habit and gender. In all tests, p<0.05
was considered statistically significant.
8
Perinatal Journal
Results
A total of 239 pregnant women were included in the
study. While mean age of the pregnant women in the
study group was 31.5±5.1, it was 28.9±4.4 in the control group (p=0.000). It was found that the mean age of
pregnant women in the study group was statistically
and significantly higher than the mean age of healthy
pregnant women. There was statistically no significant
difference between the groups in terms of gravida, parity, gestational week, weight, blood pressure, presence
of poor obstetric history and smoking habit.
When the groups were evaluated in terms of postnatal hospitalization period, it was seen that hospitalization period of the pregnant women in the study
group was 1.7±0.6 days while it was 1.5±0.5 days in the
control group (p=0.001). The hospitalization period of
the pregnant women in the study group was statistically and significantly higher than those in the control
group.
The distribution of the patients in study and control groups by demographic characteristics is shown in
the Table 1.
While 54.3% of the pregnant women in the study
group had delivered by cesarean, 45.7% of them delivered vaginally. While cesarean rate in the control group
was 44%, the rate of vaginal delivery was 56%. There
was statistically no significant difference between the
groups in terms of delivery types (p=0.116). Preterm
labor, premature rupture of membranes, gestational
hypertension, presence of preeclampsia and fetal distress, and obstetric outcomes in terms of postpartum
Table 1. Distribution of demographic characteristics according to the
groups.
Study group
(Mean±SD)
Control group
(Mean±SD)
p
0.000
Age
31.5±5.1
28.9±4.4
Weight
79.6±11.5
77.6±10.9
0.180
Gravida
2.7±1.2
2.7±1.4
0.913
0.534
Parity
1.3±0.6
1.2±0.8
Systolic blood pressure
114.3±13.6
112.1±12.2
0.188
Diastolic blood pressure
71.9±9.5
70.2±9.6
0.181
Week of gestation
38.4±1.7
38.3±1.5
0.556
Hospitalization
1.7±0.6
1.5±0.5
0.003
n (%)
n (%)
p
Smoking habit
4 (3.8)
1 (0.7)
0.101
Poor obstetric history
4 (3.8)
10 (7.5)
0.234
Perinatal outcomes of patients diagnosed borderline gestational diabetes
hemorrhage were evaluated. It was found that only postpartum bleeding was statistically and significantly higher in the study group compared to the control group
(p=0.049). The distribution of obstetric outcomes in
both groups is shown in the Table 2.
Newborn follow-up forms of 234 pregnant women
included in the study were analyzed and neonatal data
were collected. The newborns in both groups were
compared in terms of birth weights, head circumference measurements and gender distributions, and statistically no significant difference was found (p=0.188,
p=0.670, p=0.958, respectively).
While the 1-minute APGAR score of 14.2% of the
newborns in the study group was below 7, it was 12.6%
in the control group. The percentage of those with 5minute APGAR score below 7 was 2% in the study
group while it was 2.9% in the control group. No statistically significant difference was found between two
groups in terms of APGAR scores (p=0.815, p=0.599,
respectively).
No statistically significant difference was seen
between the newborns of two groups in terms of LGA,
SGA, hypoglycemia, hyperbilirubinemia, hospitalization at newborn intense care unit and neonatal mortality rates. The distribution of neonatal outcomes in
both groups is shown in the Table 3.
Table 2. Distribution of the obstetric outcomes according to the
groups.
Preterm labor
Premature rupture of membranes
Study group
n (%)
Control group
n (%)
p
4 (3.8)
9 (6.7)
0.327
13 (12.4)
8 (6)
0.083
Gestational HT
5 (4.8)
4 (3)
0.476
Preeclampsia
2 (1.9)
5 (3.7)
0.408
Fetal distress
4 (3.8)
2 (1.5)
0.258
Postpartum hemorrhage
3 (2.9)
0 (0)
0.049
Cesarean
57 (54.3)
59 (44)
0.116
Normal delivery
48 (45.7)
75 (56)
0.116
Delivery type
According to the results of few studies, many obstetricians define cases, who have positive results for 50-g
OGTT but normal results for 100-g OGTT, as glucose intolerant or borderline gestational diabetics and
recommend more frequent follow-up.[9] Yee et al.
reported advanced maternal age, multiparity and being
of Asian or Latin American ethnicity as the risk factors
for having abnormal results of glucose tolerance test in
the absence of GDM.[10] In our study, we compared the
cases in the study group who had high results in 50-g
OGTT but normal results in 100-g OGTT with the
cases in the control group and found that the age was
Discussion
GDM prevalence increases in the world and it affects
1-14% of the pregnancies. Estimated GDM prevalence
is 1.4-2.8% in a low-risk population, 3.3-6.1% in a
riskier population, and it may be more than 10% in
high-risk population.[5]
There are less data about the gestational hyperglycemia prevalence not meeting the criteria of gestational diabetes mellitus. The data received from the
Australian studies showed that 7% of all pregnant
women have hyperglycemia not meeting GDM criteria
while 5.5-8.8% of them already have GDM every
year.[6,7] There is no sufficient study in terms of blood
glucose follow-ups of this group, how to follow up
them and perinatal outcomes. Stamilio et al. confirms
that the positivity of 50-g OGTT is an independent
risk factor in terms of perinatal complications and indicates that these cases may more frequently benefit from
fetal monitorization, nutritional consultation or diabetic diet.[8]
Table 3. Distribution of the neonatal outcomes according to the
groups .
Study group Control group
(Mean±SD)
(Mean±SD)
Birth weight of neonatal
p
3224.7±446.0
3142.7±498.7
0.188
Head circumference of neonatal
34.4±1.5
34.3±1.9
0.670
n (%)
n (%)
p
1-minute APGAR score <7
15 (14.2)
17 (12.6)
0.815
5-minute APGAR score >7
3 (2)
4 (2.9)
0.599
Male
56 (53.3)
71 (53)
0.958
Female
49 (46.7)
63 (47)
0.958
SGA
2 (1.9)
7 (5.2)
0.182
LGA
2 (1.9)
5 (3.7)
0.408
Neonatal hypoglycemia
3 (2.9)
1 (0.7)
0.208
Hyperbilirubinemia
2 (1.9)
1 (0.7)
0.427
Hospitalization at newborn
intense care unit
9 (8.6)
16 (11.9)
0.400
1 (1)
1 (0.7)
0.259
Gender
Neonatal death
Volume 23 | Issue 1 | April 2015
9
Özgül G et al.
statistically and significantly high in the study group
compared to the control group.[9,11–13]
Gestational hyperglycemia not meeting the criteria
of gestational diabetes mellitus is associated with a series
of known health risks. It is known that the insulin resistance which is characteristics for the occurrence of GDM
is also associated with the development of preeclampsia.[14] In their multi-central multi-ethnical cohort study
(HAPO study), Metzger et al. evaluated 25,505 women
in terms of effects of maternal hyperglycemia on gestational outcomes and reported that there was a linear
association between preeclampsia prevalence and the
results of glucose tolerance test.[6] In our study, we found
statistically no significant difference between the study
group and the control group in terms of the gestational
hypertension and preeclampsia incidence.
Preterm labor is defined as the deliveries occurring
before 37 weeks of gestation are completed. GDM and
especially pregestational DM are known risk factors for
preterm labor. Beigelman et al. found preterm labor
rate as 10% in the study conducted on 3841 pregnant
women with GDM.[15] In our study, although preterm
labor rate was found at a lower rate in the study group
than the control group, there was no statistically significant difference between the groups.
Maternal diabetes is a risk factor for cesarean delivery. Cesarean delivery rate varies from 25% up to 80%
in diabetic women. Many factors such as diabetic complications including prematurity, macrosomia and
nephropathy are associated with high cesarean rates.[16] In
their studies, Stamilio et al. observed statistically higher
cesarean rate in cases with high results for 5 g glucose
tolerance test but normal results for 100-g OGTT compared to the cases with normal results for 50-g OGTT.[8]
Dudhbhai et al. found no significant difference between
borderline diabetic pregnant women and the control
group in terms of the cesarean rates.[13] Hong et al. investigated demographical characteristics and obstetric and
neonatal outcomes of patients with borderline gestational diabetes, and found that the cesarean rate due to fetal
distress was higher in this group than the normoglycemic pregnant women.[17] In our study, although we
found cesarean rates higher in the study group, there was
no statistically significant difference between two
groups. We also did not see any statistically significant
difference between two groups in terms of the cesarean
delivery carried out due to fetal distress.
The conditions such as episiotomy extension during vaginal delivery, vaginal laceration and postpartum
10
Perinatal Journal
atonia are observed more frequently in those who
deliver large baby. Jastrow et al. reported that the risks
for cephalopelvic disproportion, uterine rupture,
shoulder dystocia, perineal laceration and postpartum
hemorrhage due to LGA or macrosomic baby risk are
higher in mothers with maternal hyperglycemia.[18] In
our study, the postpartum hemorrhage rate was statistically and significantly higher in the study group than
the control group. We found that the most frequent
reasons for postpartum hemorrhage seen in the study
group were uterine atony followed by delivery tract
lacerations and rest placenta induced hemorrhage.
When we compared the groups in terms of maternal hospitalization periods, we found that the mothers
in the study group had statistically and significantly
longer hospitalization periods than the mothers in the
control group. In their study, Hong et al. reported statistically no significant difference between control
group and the study group with patients having borderline DM.[17] Long hospitalization periods of the
patients in our study group may be due to the high
cesarean rates and postpartum hemorrhage rates.
Figueroa et al. indicated in their studies that LGA
and macrosomia rates of the patients with borderline
gestational diabetes increased 2 and 1.6 times, respectively.[19] In the study of Bonomo et al., the authors suggested that even the slight changes in glucose intolerance may cause overgrowth in babies.[20] From 20% up
to 40% of diabetic mothers are over 90th percentile in
birth weight according to the gestation. In our study,
we found statistically no significant difference between
the groups despite the high rates of birth weight in the
study group compared to the control group.
Birth traumas, increased preterm labor rates,
obstetric conditions such as preeclampsia, and various
metabolic disorders depending on the maternal diabetes cause low APGAR scores and high level of
intense care needs in babies of diabetic mothers.[21]
Although Hong et al. found statistically no significant
difference between 1-minute and 5-minute APGAR
scores in patients with high results for 50-g OGTT but
normal results for 100-g OGTT, they reported statistically and significantly higher rates for newborn
intense care and hospitalization periods in newborns in
this group.[17] We, on the other hand, found statistically no significant difference between the groups in
terms of 1-minute and 5-minute APGAR scores, newborns’ intense care needs and neonatal mortality rates.
Perinatal outcomes of patients diagnosed borderline gestational diabetes
Dodd et al. carried out a study by using the data of
16,975 women who delivered in tertiary healthcare
organizations in Australia between 1993 and 2003, and
they found that the patients with borderline GDM had
risks for preeclampsia and cesarean and when compared to the babies of mothers with normal results for
glucose tolerance test, they indicated that the babies of
these patients had increased risks for hypoglycemia and
hyperbilirubinemia.[7] We did not observe statistically
any significant difference between two groups in terms
of neonatal hypoglycemia, hyperbilirubinemia, and
SGA and LGA baby rates. We believe that the reason
is low numbers of patients in the study and control
group, and non-availability of detailed neonatal information in the patient files analyzed retrospectively.
Conclusion
Gestational hyperglycemia not meeting the criteria of
gestational diabetes mellitus affects a great number of
pregnant women. Hyperglycemia seen during pregnancy is associated with a series of negative gestational outcomes including preeclampsia, delivery trauma and type
II DM development in mother, and future obesity, type
I and type II DM development in baby. While we do not
have certain threshold values to be categorized for establishing GDM diagnosis, the values for upper limit to initiate the treatment in order to keep blood glucose within normal limits in case of gestational hyperglycemia are
also unclear. In our study, except postpartum hemorrhage rate and hospitalization periods of the patients
with gestational diabetes, the perinatal and neonatal outcomes were similar with the outcomes of normoglycemic pregnant women. While there are researchers
recommending to refer patients with gestational hyperglycemia not meeting GDM and type II DM diagnosis
criteria to dieticians and to carry out blood glucose monitorization and follow-ups more frequently, there are
also researchers who assert that such approaches would
increase labor induction and cesarean rates, would raise
healthcare costs due to frequent examinations and investigations but not create any significant difference in
maternal and neonatal outcomes. Our knowledge on
this issue is based on limited number of randomized
studies. In order to make precise recommendations for
the management of such patients, we need further welldesigned randomized studies with larger population.
Conflicts of Interest: No conflicts declared.
References
1. Committee opinion no. 504: Screening and diagnosis of gestational diabetes mellitus. Obstet Gynecol 2011;118:751–3.
2. Gabbe SG, Niebyl JR, Galan HL, Jauniaux ERM, Landon
MB, Simpson JL, Driscoll DA. Diabetes Mellitus
Complicating Pregnancy. Obstetrics: Normal and Problem
Pregnancies. 6th ed. Philadelphia: Saunders; 2012. p: 902–4.
3. Practice Bulletin No. 137. Gestational diabetes mellitus.
Obstet Gynecol 2013;122(2 Pt 1):406–16.
4. Han S, Crowther CA, Middleton P. Interventions for pregnant women with hyperglycaemia not meeting gestational
diabetes and type 2 diabetes diagnostic criteria. Cochrane
Database Syst Rev 2012;1:CD009037.
5. Mulla WR, Henry TQ, Homko CJ. Gestational diabetes
screening after HAPO: has anything changed? Curr Diab
Rep 2010;10:224–8.
6. Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr
U, Coustan DR. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.
7. Dodd JM, Crowther CA, Antoniou G, Baghurst P, Robinson
JS. Screening for gestational diabetes: the effect of varying
blood glucose definitions in the prediction of adverse maternal and infant health outcomes. Aust N Z J Obstet Gynaecol
2007;47:307–12.
8. Stamilio DM, Olsen T, Ratcliffe S, Sehdev HM, Macones
GA. False-positive 1-hour glucose challenge test and adverse
perinatal outcomes. Obstet Gynecol 2004;103:148–56.
9. Edelman D, Olsen MK. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33(Suppl 1):S62–S9.
10. Yee LM, Cheng YW, Liddell J, Block-Kurbisch IB,
Caughey AB. 50-Gram glucose challenge test: is it indicative
of outcomes in women without gestational diabetes mellitus?
J Matern Fetal Neonatal Med 2011;24:1102–6.
11. Gumus II, Turhan NO. Are patients with positive screening
but negative diagnostic test for gestational diabetes under
risk for adverse pregnancy outcome? J Obstet Gynaecol Res
2008;34:359–63.
12. Gezer A, Esen F, Mutlu H, Oztürk E, Ocak V. Prognosis of
patients with positive screening but negative diagnostic test
for gestational diabetes. Arch Gynecol Obstet 2002;266:
201–4.
13. Dudhbhai M, Lim L, Bombard A, Jullard K, Meenakshi B,
Trachelenberg Y, et al. Characteristics of patients with
abnormal glucose challenge test and normal oral glucose tolerance test results: comparison with normal and gestational
diabetic patients. Am J Obstet Gynecol 2006;194:e42–5.
14. Wolf M, Sandler L, Munoz K, Hsu K, Ecker JL, Thadhani
R. First trimester insulin resistance and subsequent
preeclampsia: a prospective study. J Clin Endocrinol Metab
2002;87:1563–8.
15. Beigelman A, Wiznitzer A, Shoham-Vardi I, Vardi H,
Holtcberg G, Mazor M. Premature delivery in diabetes: etiology and risk factors. Harefuah 2000;138:919–23.
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16. James DK, Steer P, Weiner C, Gonik B, Crowther C,
Robson S, et al. Pregnancy and laboratory studies: a reference table of clinicians. Obstet Gynecol 2010;115:868.
17. Ju H, Rumbold AR, Willson KJ, Crowther CA. Borderline
gestational diabetes mellitus and pregnancy outcomes. BMC
Pregnancy Childbirth 2008;8:31.
18. Jastrow N, Roberge S, Gauthier RJ, Laroche L, Duperron L,
Brassard N, et al. Effect of birth weight on adverse obstetric
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Gynecol 2010;115(2 Pt 1):338–43.
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Casey B, et al. Relationship between 1-hour glucose chal-
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lenge test results and perinatal outcomes. Obstet Gynecol
2013;121:1241–7.
20. Bonomo M, Cetin I, Pisoni MP, Faden D, Mion E, Taricco
E, et al. Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial. Diabetes Metab
2004;30:237–44.
21. Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ,
Hamman RF, McDuffie RS; Kaiser Permanente of Colorado
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Original Article
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Health practices of pregnant women in
Gumushane City Center
Handan Özcan1, Nezihe K›z›lkaya Beji2
1
Vocational Health High School, Gumushane University, Gumushane, Turkey
Department of Women Health and Diseases Nursing, Florence Nightingale Faculty of Nursing, Istanbul University, Istanbul, Turkey
2
Abstract
Özet: Gümüflhane il merkezindeki gebelerin sa¤l›k
uygulamalar›
Objective: The study aimed to investigate the health practices of
pregnant women living in Gumushane city center, and to increase
awareness among pregnant women.
Amaç: Çal›flma, Gümüflhane il merkezinde yaflayan gebelerin sa¤l›k uygulamalar›n› araflt›rmak ve gebelerin fark›ndal›klar›n› artt›rmak amac›yla planlanm›flt›r.
Methods: The research is of definitive characteristics. It was conducted with a total of 189 pregnant women between October 1st
and December 10th, 2012. The data was provided as figure, percentage, arithmetic mean and standard deviation. After normality
analyses were applied to the data, Mann-Whitney U test, one-way
analysis of variance (ANOVA) test and post hoc analyses to determine the source of difference were carried out.
Yöntem: Araflt›rma tan›mlay›c› niteliktedir. 1 Ekim – 10 Aral›k
2012 tarihleri aras›nda toplam 189 gebeyle gerçeklefltirilmifltir.
Veriler; say›, yüzde, aritmetik ortalama ve standart sapma ile verilmifltir. Verilere normallilik analizleri uygulamas› sonras› MannWhitney U testi, tek yönlü varyans analizi (ANOVA) testi, farkl›l›klar›n kayna¤›n› belirlemek amac›yla post hoc analizler yap›lm›flt›r.
Results: The ages of pregnant women are between 19- and 48-yearold, and the mean age is 29.09±5.5. Of the participants, 65.1% of
them stated that their expenses were equal to their incomes, 8.58%
of them had no social security, 24.6% of them had a job, and 51.3%
of them were living in the city center. Statistically significant difference was found in the ANOVA test analysis carried out among the
score averages of the “Health Practices Questionnaire” according to
the educational background of the spouses of the pregnant women.
Difference was found between primary school and university graduates. Score average of the “Health Practices Questionnaire” for
those living in metropolises was higher than those living in villages;
it was found that the score average of the questionnaire decreased as
the age increased.
Bulgular: Gebelerin yafllar› 19–48 yafl aral›¤›nda olup, ortalama
29.09±5.5’dir. Kat›l›mc›lar›n %65.1’i gelirlerinin giderlerine eflit
oldu¤unu, %8.58’inin sosyal güvencesi olmad›¤›n›, %24.6’s› çal›flt›¤›n›, %51.3’ü il merkezinde yaflad›¤›n› söyledikleri tespit edilmifltir. Gebelerin efllerinin e¤itim düzeylerine göre ‘Gebelikte
Sa¤l›k Uygulamalar› Ölçek’ puan ortalamalar› aras›nda yap›lan
ANOVA testi analizinde istatistiksel aç›dan anlaml› fark elde edilmifltir. ‹lkokul ve üniversite mezunlar› aras›nda farkl›l›k oldu¤u
saptanm›flt›r. Büyük flehirlerde yaflayanlar›n ‘Gebelikte Sa¤l›k Uygumalar› Ölçek’ puan ortalamas›, köylerde yaflayanlardan daha
yüksek bulunmufl ve yafl›n artmas› ile ölçek puan ortalamas› da
düflmektedir.
Conclusion: For the health practices during pregnancy, the ages of
pregnant women and their spouses and living in whether in urban or
rural areas caused differences. It is required to extend “prenatal and
postnatal training programs” among pregnant women and their
families, to enable the spouses of pregnant women to join such programs by informing them, to carry out detailed interviews in order
to evaluate and modify the practices of pregnant women in advanced
age group, and to increase awareness on this subject matter.
Keywords: Pregnancy, health behavior, education.
Sonuç: Gebelikte sa¤l›k uygulamalar›nda; gebenin kendisinin ve
eflinin yafllar›n›n, yaflad›¤› alan›n kentsel ya da k›rsal olmas›n›n
farkl›l›klara sebep oldu¤u görülmüfltür. Gebelere ve ailelerine yönelik “prenatal ve postnatal e¤itim programlar›n›n” yayg›nlaflt›r›lmas›, gebelerin efllerinin de bilgilendirilerek bu programlara kat›l›m›n›n sa¤lanmas›, ileri yafl grubundaki gebelerin uygulamalar›n›n
de¤erlendirilmesi ve düzeltilmesi ad›na ayr›nt›l› görüflmelerin yap›lmas› ve bu konuda fark›ndal›klar›n›n artt›r›lmas› gerekmektedir.
Anahtar sözcükler: Gebelik, sa¤l›k davran›fl›, e¤itim.
Correspondence: Handan Özcan, MD. Gümüflhane Üniversitesi Sa¤l›k Hizmetleri
Meslek Yüksekokulu, Gümüflhane, Turkey. e-mail: hndnozcn@hotmail.com
Received: April 7, 2014; Accepted: December 1, 2014
Please cite this article as: Özcan H, K›z›lkaya Beji N. Health practices of pregnant
women in Gumushane City Center. Perinatal Journal 2015;23(1):13–19.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231003
doi:10.2399/prn.15.0231003
QR (Quick Response) Code:
Özcan H, K›z›lkaya Beji N
Introduction
According to the data of TNSA-2008, a woman who
reaches at the end of her fertility age in Turkey gives
2.16 births on average. Total fertility rate today is 50%
lower than the rate in 1970s. In Turkey, fertility piles up
in the age group 20–29. An average woman has her first
child at 25-year-old, and two children at 30-year-old.
Fertility period diminishes swiftly after 30-year-old, and
reaches a negligible level at 40s.[1]
Health practices of women during pregnancy affect
both maternal and neonatal health both during pregnancy and postpartum period. Health practices during pregnancy can be defined as the activities including the
health of pregnant woman, fetus and newborn and
affecting the gestational outcome. Health practices
which are significant for gestational outcomes should be
identified and earned during prenatal care. These practices should include various topics such as dental care,
not smoking, not using alcohol or illegal substances, balanced nutrition and gaining appropriate amount of
weight, regular exercising, having training about pregnancy and labor, and avoiding risky sexual acts or exposure to other infection factors.[2] As well as going for regular health checks, proper nutrition and resting habits,
factors such as knowing regular course of pregnancy and
possible gestational complications, and choosing right
information source also directly affect the quality of gestational period.[3] Dental care and checks during pregnancy are very important in terms of fetal health. The
studies show that more than one third of women have
dental problems.[4] Risky conditions such as preterm
labor, baby with low birth weight and preeclampsia are
seen in those who have periodontal problems during
pregnancy. Mothers should be encouraged for dental
checks.[5]
Smoking during and after pregnancy causes significant health issues for fetus, newborn and child. Active
smoking is one of the major reasons for various health
risks such as preterm labor, miscarriage, postpartum
hemorrhage, ectopic pregnancy, fetus with low birth
weight and placenta praevia.[6] Smoking during the first
trimester is one of the major factors increasing the risks
for spontaneous abortion and ectopic pregnancy.[7] It was
reported that the risk for ectopic pregnancy is 1.5 – 2.5
higher in smoking women.[8]
Physical activity is important for a healthy life. The
importance of exercising during pregnancy is empha-
14
Perinatal Journal
sized in the literature.[9] It is reported that exercising is
useful for pregnant women who have no obstetric and
medical complication, and physical activity is recommended minimum 30 minutes weekly in order not to
have any gestational complication.[10] Direct heavy physical activities, competitive sports increasing cardiac
rhythm and prolonged activities on supine position are
not recommended.[11] The recent studies in particular
have highlighted that physical activities have a significant role for a healthy pregnancy.[12,13] Problems such as
fatigue particularly, physical discomfort, being unable to
use time efficiently and incompetency in child care are
seen more in pregnant women who do not engage in
physical activities.[14-16]
High quality care and balanced nutrition during
pregnancy is very important for the maternal health.[17]
As the education, health and nutrition condition, socioeconomic life standards and provided healthcare services of mother improve, the chance to have a successful
pregnancy also increases. A successful pregnancy and
delivery ensure babies to born into a healthy life.[18]
Maintaining pregnancy healthy for both mother and
baby requires medical checks from the beginning up to
the end of pregnancy. In normal pregnant women, prenatal checks are estimated to be once a month until the
28 weeks of gestation, once every 15 days between 28
and 36 weeks of gestation and once a week from the 36
weeks of gestation up until delivery. According to the
Ministry of Health, it is aimed to follow up each pregnant woman at least for 6 times by identifying as of the
beginning of pregnancy. Making visits regularly ensures
to decrease fetal and neonatal problems.[19]
Vaccination programs have a significant role especially to decrease infant deaths. According to the World
Health Organization (WHO), 1/5 of the infant deaths in
developing countries are caused by the preventable diseases. Thanks to the “Expanded Program on
Immunization” initiated by WHO in 1974, considerable
decreases have been observed in the incidence, mortality
and morbidity rates of preventable diseases by vaccination.[20] Main purposes of vaccination are to protect fetus
during pregnancy against infections such as varicella and
rubella causing congenital malformation, growth retardation, stillbirth and neurological sequels, to protect
mother against diseases such as influenza, hepatitis B
which progress more severely during pregnancy, and to
decrease infant morbidity, mortality and infectious dis-
Health practices of pregnant women in Gumushane City Center
ease risk of newborn in the first 6 months.[21] There are
significant differences in vaccination rates according to
the region, residential area and educational background
of mother. The percentage of fully vaccination children
is significantly low in the Eastern Anatolia Region
(64%). It is followed by Northern and Southern Regions
(84% and 82%, respectively).[1]
Postpartum care is very important both for mother
and baby. Considerably majority of them are being
physicians, 82% of women had postpartum care. Four
out of five women had their first postnatal check within
two days after the delivery. Postpartum care and its timing vary according to the regions. The rate of having
care within first 41 days is the highest among the women
in Aegean Region (92%), and the rate of women in MidEastern Anatolia is only 55%.[1] The care to be provided
to mother and baby is very significant for facilitating the
adaptation of mother to postpartum period, early start of
and sustaining lactation, providing mother-baby interaction, accelerating healing process, preventing complications, and for the postnatal comfort.[22]
The study aimed to investigate the health practices
of pregnant women living in Gumushane city center,
and to increase awareness among pregnant women.
‘Rarely (b)’ as 2 points, ‘Sometimes (c)’ as 3 points,
‘Frequently (d)’ as 4 points and ‘Always (e)’ as 5 points;
each question from 18 to 34 has 5 appropriate options
which are scaled from 1 to 5 points. Some questions
have reverse scaling. These are the questions 6, 7, 8, 22,
23, 24, 25, 26, 27, 33 and 34. The points of these questions are scaled from 5 to 1, in a reverse way. A general
point is obtained from the total of the all questions.
Getting high score represents high quality health behavior which has a significant benefit on pregnancy. In the
study of Lindgreen, the lowest possible score in the scale
is 34 while the highest possible score is 170.[2] The
method of face-to-face interview was applied in the data
collection. After the questionnaire, health practice trainings were provided to pregnant women.
SPSS software was used for the analysis of the data.
The data obtained in the study was provided as figure,
percentage, arithmetic mean and standard deviation.
After normality analyses were applied to the data,
Mann-Whitney U test, one-way analysis of variance
(ANOVA) test and post hoc analyses to determine the
source of difference were carried out. p<0.05 was considered as significant.
Results
Methods
The research is of definitive characteristics. A total of
233 pregnant women visiting the maternity clinic for
pregnancy control between October 1st and December
10th 2012 were accessed and only 189 of them accepted to participate in the study.
During the period when the investigation was
planned and it was started to collect the data, written
permission was received from Gumushane Provincial
Directorate of Health. All participants were informed
and read the purposes and methods of the investigation.
The data collection tool used in the investigation has
two parts. The first part of the form, which is intended
for personal information, performs a literature review
and it includes 25 questions such as age, educational
background, employment status, health insurance, residential area, family type, pregnancy follow-up, and child
number. The second part of the form is “Health
Practices Questionnaire” (HPQ). HPQ-II is a questionnaire with 34 questions. Questions from 1 to 17 include
five-point likert scale varying between “Always” and
“Never”. The answer ‘Never (a)’ is calculated as 1 point,
Mean age of the pregnant women is 29.09±5.5 (min:
19, max: 48). Of the participants, 65.1% of them stated that their expenses were equal to their incomes,
8.58% of them had no social security, 24.6% of them
had a job, and 51.3% of them were living in the city
center (Table 1).
While 66.7% of the pregnant women preferred to
visit an obstetrician at state hospital, 6.8% of them visited obstetricians both at private hospital and state hospital. Of the pregnant women, 60.6% said that they
had pregnancy follow-up for 5 times or more, 75.4% of
them became pregnant voluntarily, 72.3% of them had
health practice training before pregnancy (from internet, those with pregnancy experience, TV, family
physician, nurse), and 89.3% of them said that they
would like to be informed about health practices. Only
1.7% of the participants had the history of sexually
transmitted disease (Table 2).
Of the spouses, 10.1% were primary school graduate, 14.9% were secondary school graduate, 51.1%
were high school graduate, and 23.9% were university
graduate. While 2.6% of them were unemployed,
Volume 23 | Issue 1 | April 2015
15
Özcan H, K›z›lkaya Beji N
Table 1. Distribution of pregnant women according to definitive characteristics (n=189).
Table 2. Pregnancy history of participants.
Pregnancy history
Definitive characteristics
Number
Number
%
Planning the pregnancy (n=183)
I got pregnant accidentally
I got pregnant on purpose
I got pregnant accidentally but I want to deliver
37
138
37
20.2
75.4
4.4
Health checks during pregnancy (n=188)
Once
Twice
Three times
Four times
Five times or more
13
17
22
22
114
6.9
9.0
11.7
11.7
60.6
Number of pregnancy
First pregnancy
Second pregnancy
Third pregnancy
Fourth pregnancy
Fifth pregnancy or more
55
61
43
17
6
30.2
33.5
23.6
9.3
3.3
Having training on health practices during
pregnancy (n=188)
Yes
No
136
51
72.3
27.1
%
Age (n=189)
15–24
25–34
35 and above
43
112
34
22.8
59.3
18.0
Educational background (n=188)
Primary school
Secondary school
High school
University
48
51
62
27
25.5
27.1
32.9
14.4
Residential area (n=189)
Metropolis
City center
County
Village
9
97
56
27
4.8
51.3
29.6
14.3
Profession (n=187)
Housewife
Civil service
Worker
Self-employed
Other
141
31
6
5
4
75.4
16.6
3.2
2.7
2.1
Income level (n=186)
Income less than expenses
Income equals to expenses
Income higher than expenses
27
121
38
14.5
65.1
20.4
Performer of the follow-ups during pregnancy (n=168)
Family physician
4
Private obstetrician
41
Obstetrician at state hospital
112
Other
1
ence was caused by the mean values of first group (age
range of 15-24) and third group (35-year-old and
above), and that the score average of the questionnaire
decreased as the age increased (Table 3).
39.7% of them were civil service employees, 32.8% of
them were worker, 18.5% of them were self-employed
and 6.3% of them were engaged in other fields.
The mean score of the participants for health practice questionnaire (HPQ) was 111.76±18.53.
Statistically no significant difference was observed in
the analysis of ANOVA test carried out in the HPQ
scores according to the educational background of pregnant women (p>0.05) (Table 4).
In the analysis of ANOVA test performed between
age groups of pregnant women and mean HPQ scores,
statistically a significant difference was found.
According to the post-hoc analysis to determine the
source for the difference, it was found that the differ-
The average HPQ scores were also analyzed
according to the employment status of pregnant
Table 3. Distribution of mean HPQ scores according to age groups of pregnant women.*
Mean HPQ Score
Age group
N
X
SS
15–24
43
117.4884
12.56862
25–34
112
110.6786
20.69174
35 and above
33
107.9697
15.88924
Total
188
111.7606
18.53660
*ANOVA test was used.
16
Perinatal Journal
2.3
24.4
66.7
1.7
F
P
2.996
0.052
Health practices of pregnant women in Gumushane City Center
Table 4. Distribution of mean HPQ scores according to educational background of pregnant women.*
Mean HPQ Score
Educational background
N
X
SS
Primary school
47
109.8298
15.94190
Secondary school
51
111.6667
21.24116
High school
63
112.6190
17.50615
University
27
113.2963
20.30312
Total
188
111.7606
18.53660
F
P
0.274
0.844
*ANOVA test was used.
women. There was no significant difference in the
Mann-Whitney U analysis performed between the
employment statuses and mean HPQ scores of pregnant women (Table 5).
graduate. According to TNSA 2008 data, about 52%
of women were only primary school graduates. In the
study, 73% of women were secondary school or higher level graduates.
In the analysis of ANOVA test performed on mean
HPQ scores according to the educational background
of the spouses of pregnant women, statistically a significant difference was found. In the post-hoc analysis
carried out for determining the source of difference, it
was seen that there was difference between primary
school graduates and university graduates.
In Turkey, the lowest employment rate among
women was in Central and Eastern Regions.[1] Our
study, we observed that the rates of unemployed
women in Gumushane, which is a province in the Black
Sea Region, were high similar to the women living in
Central and Eastern Regions.
Discussion
While 51.3% of the women participated in the
study were living in the large city, 29.6% of them were
living in counties, 14.3% of them in villages, and 4.8%
of them in the city. The most of the pregnant women
being living in the city and the metropolis is important
in terms of having follow-up, care and training during
pregnancy. In our study, we found statistically a significant difference in the analysis of ANOVA test performed on mean HPQ scores according to the most
frequent residential area of pregnant women. The
mean scores of those living in the city were higher than
those living in the villages.
While 82.1% of the participants were in the 15–34 age
range, 47.6% of them were high school and university
It is known that carrying out the delivery in healthy
conditions and getting postpartum follow-ups regular-
In the analysis of ANOVA test performed on mean
HPQ scores according to the most frequent residential
areas of pregnant women, statistically a significant difference was found. A post-hoc analysis was performed
for the difference, and the p value was found as <0.05
for the difference between the average values of those
living in urban and rural areas. The mean HPQ scores
of pregnant women living in the city center were found
to be higher than those living in villages.
Table 5. Distribution of mean HPQ scores according to employment statuses of pregnant women.*
Mean HPQ Score
Employment status
N
X
140
83.24
Employed
31
98.47
Total
171
Unemployed
SS
U
P
18.536
1783.50
0.121
*Mann-Whitney U test was used.
Volume 23 | Issue 1 | April 2015
17
Özcan H, K›z›lkaya Beji N
ly decrease maternal and perinatal newborn deaths.[23]
Total visits before the delivery is a significant indication for evaluating the sufficiency of prenatal care.
While pregnant women need to have follow-ups for 6
times during the pregnancy, insufficient number of visits shows that this service is not carried out actively.[24]
Although the mean HPQ scores in the study are low,
the rate of participants to visit a health institution during pregnancy for five or more times is 60.6%.
their families, to enable the spouses of pregnant
women to join such programs by informing them, to
carry out detailed interviews in order to determine the
mistakes and to modify the practices of pregnant
women in advanced age group, and to increase awareness on this subject matter.
In the analysis of ANOVA test performed on mean
HPQ scores according to the educational background
of the spouses of pregnant women, statistically a significant difference was found. As the educational background increases, HPQ score also increases. Similarly,
as in the study of Çakmakç› and Eser, there was statistically a significant difference between the pregnant
women whose spouses were university/college graduate and those whose spouses were high school or lower
level graduates.[25]
References
In the analysis of ANOVA test performed on the
mean HPQ scores according to the age groups of pregnant women, statistically a significant difference was
found. Mean HPQ score of young pregnant women
was 117.48 while it was 107.96 for pregnant women
with advanced ages. The reason for difference based on
age may be that young group tries to learn by searching studies as a source of information, and that the
advanced age group utilizes their experience.
The results of our study are similar to the studies
performed to analyze the effects of age and educational background of women on gestational health. The
major factors increasing the possibility to carry out a
delivery in a healthcare institution are the young ages
of women, early in the rank of birth order, mother having high number of prenatal care and high level of education. It has been reported that the possibility to
deliver a baby in a healthcare institution in an urban
area is 1.2 times higher than rural areas, and the rate of
home birth is higher in Eastern Regions than Central
Anatolian Regions (27%).[1,19]
Conclusion
For the health practices during pregnancy, the ages of
pregnant women and their spouses and living in
whether in urban or rural areas caused differences.
Therefore, it is required to extend “prenatal and postnatal training programs” among pregnant women and
18
Perinatal Journal
Conflicts of Interest: No conflicts declared.
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19. Turan T, Ceylan S, Teyikçi S. Annelerin düzenli prenetal
bak›m alma durumlar› ve etkileyen faktörler. F›rat Sa¤l›k
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24. Taflk›n L. Kad›n Sa¤l›¤› ve Hastal›klar› Hemflireli¤i. XI.
bask›. Ankara: Sistem Ofset Matbaac›l›k; 2012. p: 67–80.
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Original Article
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The evaluation of pregnancies complicated by
eclampsia: retrospective analysis of
37 cases in our clinic
Aytekin Tokmak, Korkut Da¤lar, Ali ‹rfan Güzel, Bergen Laleli, Salim Erkaya, Dilek Uygur
Gynecology & Obstetrics Clinic, Zekai Tahir Burak Maternal Health Training and Research Hospital, Ankara, Turkey
Abstract
Özet: Eklampsi ile komplike olan gebeliklerin
de¤erlendirilmesi: Klini¤imizdeki 37 olgunun
retrospektif analizi
Objective: We aimed to evaluate the clinical characteristics and
maternal and perinatal outcomes of pregnancies complicated by
eclampsia.
Amaç: Eklampsi ile komplike olan gebeliklerin klinik özelliklerinin ve maternal ve perinatal sonuçlar›n›n de¤erlendirilmesi.
Methods: A total of 37 patients were identified who were diagnosed
and treated in Zekai Tahir Burak Maternal Health Training and
Research Hospital between January 2009 and December 2013.
These patients found in and reviewed by their hospital records were
evaluated retrospectively in terms of their clinical characteristics,
laboratory parameters, and maternal and perinatal outcomes.
Results: It was found that a total of 89,908 deliveries were performed in our hospital during the study. Eclampsia incidence was
calculated as 0.4/1000 deliveries. Mean age of the cases in our study
was 27.2±6.6 years and mean gestational age was 33.2±4.5 weeks.
The rate of the cases who were nullipara was 78.4%. It was understood that the most of the eclamptic seizures occurred during the
antenatal period (59.6%) after 28 weeks of gestation (89.2%).
Neonatal morbidity rate was 61.1% and perinatal mortality rate was
12.5%. While major morbidity rate was 43.2%, the leading cause of
the morbidity was HELLP syndrome (37.8%). It was found that a
thirty-year-old woman who was multipara (G2P1) died on the postpartum 10th day due to intracranial hemorrhage.
Conclusion: Eclampsia is one of the most significant reasons of
maternal and perinatal morbidity and mortality. Even though it is not
always possible to prevent it, the best approach can be provided by
ensuring patients with highest risk for eclampsia to have regular antenatal care, preventing convulsions through hospitalization in tertiary
healthcare centers with proper conditions, bringing blood pressure
under control and carrying out delivery at the most convenient time.
Keywords: Eclampsia, clinical characteristics, maternal and perinatal outcomes.
Yöntem: Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rma
Hastanesinde Ocak 2009 ve Aral›k 2013 tarihleri aras›nda eklampsi tan›s› konulan ve tedavi edilen toplam 37 hasta tan›mland›. Hastane kay›tlar›ndan saptanan ve dosyalar› incelenen bu hastalar klinik özellikleri, laboratuvar parametreleri ve maternal ve perinatal
sonuçlar›na göre retrospektif olarak de¤erlendirildi.
Bulgular: Çal›flma süresince hastanemizde toplam 89.908 do¤umun gerçekleflti¤i saptand›. Eklampsi insidans› 0.4/1000 do¤um
olarak hesapland›. Çal›flmam›zda yer alan olgular›n yafl ortalamas›
27.2±6.6 y›l ve ortalama gebelik yafl› 33.2±4.5 haftayd›. Olgular›n
%78.4’ü nullipar idi. Eklamptik nöbetlerin ço¤unlu¤unun antenatal dönemde (%59.6) ve 28. gebelik haftas›ndan sonra (%89.2)
gerçekleflti¤i anlafl›ld›. Neonatal morbidite oran› %61.1 ve perinatal mortalite oran› %12.5 olarak bulundu. Majör morbidite oran›
%43.2 ve morbiditeye neden olan önde gelen sebep HELLP sendromuydu (%37.8). Otuz yafl›nda multipar (G2P1) bir kad›n›n,
do¤umdan sonra 10. günde intrakranial kanama nedeniyle kaybedildi¤i saptand›.
Sonuç: Eklampsi, maternal ve perinatal morbidite ve mortalitenin
en önemli nedenlerinden biridir. Her zaman önlenemese de, eklampsi geliflme riski yüksek olan hastalar›n düzenli antenatal bak›m
almalar›n›n sa¤lanmas›, uygun koflullara sahip üçüncü basamak
merkezlerde hospitalize edilerek, konvülziyonlar›n önlenmesi, kan
bas›nc›n›n kontrol alt›na al›nmas› ve uygun zamanda do¤umun
gerçeklefltirilmesi ile en iyi yaklafl›m sa¤lanabilir.
Anahtar sözcükler: Eklampsi, klinik özellikler, maternal ve perinatal sonuçlar.
Correspondence: Aytekin Tokmak, MD. ZTB Kad›n Sa¤l›¤› E¤itim ve Arafl. Hast.
Kad›n Hastal›klar› ve Do¤um Klini¤i, Ankara, Turkey. e-mail: aytekintokmak@gmail.com
Received: November 2, 2014; Accepted: January 5, 2015
Please cite this article as: Tokmak A, Da¤lar K, Güzel, A‹, Laleli B, Erkaya S,
Uygur D. The evaluation of pregnancies complicated by eclampsia: retrospective
analysis of 37 cases in our clinic. Perinatal Journal 2015;23(1):20–25.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231005
doi:10.2399/prn.15.0231005
QR (Quick Response) Code:
The evaluation of pregnancies complicated by eclampsia
Introduction
Methods
Hypertensive disorders are the most frequent medical
complication of pregnancy, and it has been reported
that they affect 5-10% of pregnancies in the USA.[1]
Despite its higher incidence and wider incidence range
in developing countries, its incidence rate (0.16–
1/1000 delivery) is stable in developed countries.[2]
Eclampsia is a specific neurological complication of
pregnancy, it is characterized by hypertension and
tonic clonic convulsions, and its pathophysiology is still
unclear. It has been found that the cerebral anomalies
developing in eclampsia are similar to the changes in
hypertensive encephalopathy.[3] Early marriage, nulliparity, insufficient prenatal care, low socio-economical
condition and malnutrition are the risk factors for
eclampsia as in preeclampsia. While eclamptic seizure
may develop after severe preeclampsia, it also may
develop unexpectedly without hypertension and proteinuria.[4] A mild hypertension can be seen only in 3060% of the women developing eclampsia.[3] Headache,
blurring of vision, photophobia and mental changes
may be early diagnoses of an approaching eclampsia;
however, the eclampsia may develop even without
these findings.
Thirty-seven cases who were established eclampsia
diagnosis and treated in high-risk pregnancy and delivery room departments of Zekai Tahir Burak Maternal
Health Training and Research Hospital between
January 2009 and December 2013 were evaluated retrospectively. Patient data were obtained from patient
files. Demographic characteristics, laboratory findings
and obstetric outcomes were recorded. For each
women, age, gravida, parity, abortion, gestational body
mass index (BMI), blood pressure measurements, week
of gestation at diagnosis, additional disease, smoking
habit, initial symptoms, educational level, the phase
that delivery occurs, laboratory findings, hospitalization period, magnesium application, delivery type,
birth weight, Apgar score, and finally maternal - fetal
morbidity and mortality were investigated. It was seen
that the weeks of gestation were calculated according
to last menstrual periods, and that the gestational age
was noted according to ultrasound screenings carried
out on the first trimester in those who did not know
their last menstrual period. Full urinalysis, full blood
counts, liver and kidney function tests and LDH values
of all cases were recorded. It was found that fetal biometry and Doppler examination by ultrasonography
and continuous external fetal monitorization by cardiotocography were carried out for each patient. With
12-hour dosing interval, 12 mg betamethasone was
administered to all pregnant women at or below 34
weeks of gestation for fetal lung maturation.
Eclampsia is a life-threatening complication of
pregnancy. Its most frequently reported reason is
HELLP syndrome.[3] Maternal mortality rate of
eclampsia was reported was as high as 15%.[5]
Intracranial hemorrhage, pulmonary edema, renal,
hepatic and respiratory failures are the leading mortality reasons. Increased perinatal mortality is a result of
eclampsia, and perinatal mortality rate was reported as
10% in a multicentric study carried out in Brazil.[6]
Chronic placental insufficiency, preterm labor and
ablatio placentae are among perinatal mortality reasons.[7] It is easy to establish eclampsia diagnosis; however, it should be remembered that conditions such as
epilepsy, encephalitis, meningitis, brain tumors, cysticercosis and ruptured brain aneurysm may trigger
eclampsia during advanced weeks of gestation and
puerperium. All pregnants having convulsion should
be considered as eclamptic until all other reasons are
ruled out.[8] Eclampsia requires immediate treatment in
order to minimize maternal and fetal morbidity and
mortality. In this study, we aimed to analyze eclampsia
cases in our hospital which is a tertiary healthcare center in Central Anatolia.
Eclampsia was identified according to the presence
of following criteria: the presence of at least two among
hypertension, proteinuria, thrombocytopenia, and
increased serum AST level within 24 hours after convulsions developed during pregnancy or within 10 days
during following delivery. The diagnosis of HELLP
syndrome was established according to hemolysis (LDH
>600 U/L), thrombocytopenia (<100×103/μL) and
increased liver enzyme (AST>70U/L). It was found that
10-minute intravenous loading dose of 4.5 g magnesium
sulphate (MgSO4) was administered to all women having
eclamptic seizure and then convulsion prophylaxis was
initiated so as to progress as 2 g/h intravenous infusion,
and nifedipine and alpha-methyldopa were used in the
anti-hypertensive treatment in order to keep diastolic
blood pressure between 90 and 100 mmHg and severe
hypertension under control.
Volume 23 | Issue 1 | April 2015
21
Tokmak A et al.
Statistical Package for the Social Sciences (SPSS)
version 15.0 (SPSS Inc., Chicago, IL, USA) was used
for statistical analysis. Definitive data and frequencies
were calculated by the computer. Conformity of the
data to normal distribution was evaluated by
Kolmogorov-Smirnov test. The data with constant and
normal distribution were provided as mean±standard
deviation, and the data without constant and normal
distribution were provided as median (minimum-maximum). Categorical variables were given as figure (percentage).
Results
During the 5-year period of the study, a total of 89,908
deliveries occurred in our hospital. It was found that 37
of these pregnancies were complicated with eclampsia.
Eclampsia incidence was calculated as 0.4/1000 deliveries. Eclampsia was more common in nullipara cases
(78.4% vs. 21.6%). Mean age and weeks of gestation of
the patients were 27.2±6.6 (range: 16 to 42) years and
33.2±4.5 (range: 25 to 39) weeks, respectively. While
mean systolic blood pressure value was 155.7±26.9
mmHg, it was 101.6±17.5 mmHg for diastolic blood
pressure. The clinical and laboratory findings of the
patients are shown in the Table 1. Eclamptic seizure
occurred during antepartum period in 22 patients, during postpartum period in 10 patients and during intrapartum period in 5 patients. Eclamptic seizure developed without hypertension in 5 patients, and headache
was the most frequent initial symptom (Table 2). The
rates of cesarean and vaginal delivery were 89.2% and
10.8%, respectively. Two out of 4 patients who had
vaginal delivery developed postpartum eclampsia, one
patient had intrauterine fetal death and one multipara
patient developed intrapartum eclampsia on the second
phase of the delivery. The educational level of more
than half of the patients was primary school or below.
One patient had gestational diabetes while one patient
had smoking history. Multiple pregnancy was found in
two patients (one twin, and one triplet). It was seen in
two patients that eclampsia developed without proteinuria. While maternal morbidity developed in 16
patients, the diagnosis of HELLP syndrome was established in 14 of them, disseminated intravascular coagulation (DIC) in one patient, sudden temporary loss of
vision in one patient and renal failure following
detachment in one patient. It was found that one
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Perinatal Journal
Table 1. Clinical and laboratory characteristics of cases.
Variable
Result
Age (year)*
27.2±6.6
Nullipara†
29 (78.4)
Gravida‡
2 (1–6)
Parity‡
0 (0–3)
Abortion‡
BMI (kg/m2)*
Smoking†
1 (0–6)
29.8±4.8
1 (2.7)
Educational level†
Illiterate
2 (5.4)
Primary school
17 (45.9)
Secondary school
8 (21.6)
High school
10 (27)
SBP (mmHg)*
155.7±26.9
DBP (mmHg)*
101.6±17.5
Hospitalization period (day)*
8.6±3.3
AST (U/L)*
236.2±458.9
ALT (U/L)*
176.8±305.1
Creatinine (mg/dL)*
0.7±0.2
Platelet (x103/μL)*
179.4±108.6
LDH (U/L)*
1008.4±705.9
Proteinuria in spot urine (mg/dL)†
0
0< and ≤30
>30 and ≤300
>300
2 (5.4)
3 (8.1)
22 (59.5)
10 (27)
BMI: Body mass index; DBP: Diastolic blood pressure; SBP: Systolic blood pressure. Data *: 9±SD; †: n(%); ‡: median (minimum–maximum).
patient was referred to the Intense Care Unit of
Anesthesiology and Reanimation Department of
Ankara Training and Research Hospital due to
intracranial hemorrhage, but died on the way.
Maternal mortality was found as 2.7% due to this case.
Prematurity and intrauterine growth retardation
(IUGR) were the most frequent reasons for perinatal
morbidity (Table 3). Perinatal mortality rate was
found as 12.5% (5/40).
Table 2. Initial symptom.
Symptom
n (%)
Headache
10 (27)
Blurring of vision
8 (21.6)
Epigastric pain
2 (5.4)
Recurring seizure
5 (13.5)
The evaluation of pregnancies complicated by eclampsia
Discussion
Eclampsia is a life-threatening gestational complication developing acutely. It has a high risk of morbidity
and mortality for mother and fetus. When eclampsia
usually occurs following severe preeclampsia, it may
appear without any preeclamptic symptoms. Munro[9]
reported that 38% of eclamptic seizures occurred without any symptom and finding previously. Its incidence
reported in developed countries is 1/2000–1/3000;
however, this rate is much more in developing countries.[4] The eclampsia rates reported in Turkey vary. In
their study, Y›ld›r›m et al.[10] investigated 113 eclampsia
cases and found eclampsia rate as 1.2/1000 delivery,
which was reported as 1.7/1000 in another study carried in the western region of Turkey.[11] The study performed in Southeastern Anatolia found the incidence
rate as 19/1000[12] while it was reported as 1.2/1000 in
Northeastern Anatolia.[13] In our study, we found a
lower rate which was 0.4/1000 (1/2430). The reason
may be that especially the eclampsia cases developing
during the postpartum period referred to other multidisciplinary hospitals in the region.
Liu et al.[14] found that eclampsia incidence gradually decreased and nulliparity, anemia and the presence
of cardiac disease in singleton deliveries increased the
risk of eclampsia for 2.3–4.8 times. In another study, it
was argued that being younger than 20-year-old and
older than 35-year-old, long intervals between deliveries, low socio-economic level, gestational diabetes, gestational obesity and gaining weight during pregnancy
less or more than recommended were found to be the
risk factors associated with eclampsia, and that multiparity and smoking decreased the eclampsia.[15] Y›ld›r›m
et al. showed in their studies that 63.7% of eclamptic
seizures developed in nullipara cases.[10] Similarly, we
found in our study that nulliparity was more common
among eclamptic cases (78.4%).
Lopez-Llera[16] categorized eclampsia according to
the onset time of the seizure and defined as antepartum
if it develops before delivery, as intrapartum if it occurs
during delivery and as postpartum if it develops within
7 days after delivery. It was reported that 38–53% of
the eclamptic seizures developed during antepartum
period while 11–44% of them developed during postpartum period.[3] However, it can be difficult to distinguish them since antepartum and intrapartum periods
intertwine. Also, in higher than 90% of the eclamptic
Table 3. Obstetric and maternal-perinatal outcomes.
Variable
Result
Week of gestation*
33.2±4.5
≤28 week of gestation†
4 (10.8)
Birth weight*
1988.9±973.6
Apgar score‡
6 (0–9)
Multiple pregnancy†
Twin
1 (2.7)
Triple
1 (2.7)
Perinatal morbidity†
Prematurity
22 (61.1)
IUGR
12 (32.4)
Perinatal mortality†
5 (12.5)
Maternal complication†
16 (43.2)
HELLP
14 (37.5)
Maternal mortality†
Delivery
1 (2.7)
type†
Vaginal delivery
4 (10.8)
Cesarean section
33 (89.2)
Period that seizure occurred†
Antepartum
Postpartum
Intrapartum
22 (59.5)
10 (27)
5 (13.5)
IUGR: Intrauterine growth retardation. Data *: 9±SD; ‡: n(%); ‡: median (minimum–maximum).
cases, it develops after 28 weeks of gestation.[4] In line
with the literature, we observed eclamptic seizure in
most of our cases during antepartum period (59.4%)
and after 28 weeks of gestation (89.2%).
The first step of eclampsia management is to prevent
maternal injuries and to provide cardiopulmonary support. Afterwards, it is to prevent the recurrence of convulsions and to decrease blood pressure to the safe levels. There are strong evidences for using routine magnesium sulphate (MgSO4) for the prophylaxis of seizures in
the literature, and a full consensus has been reached.[17,18]
The recommendation for patient with eclamptic seizure
is to administer 1–2 g/h maintenance dose for at least 24
hours after 4–6 g intravenous loading dose.[1] However,
in 9.4% of the cases, it was reported that eclamptic
seizures may recur despite MgSO4 prophylaxis.[17] We
initiate MgSO4 prophylaxis for all our severe preeclamptic and eclamptic patients. We monitor our patients by
their urination, respiratory rate, patellar reflex and intermittent serum magnesium levels. In our study, similar to
the literature, the seizure recurred under MgSO4 proVolume 23 | Issue 1 | April 2015
23
Tokmak A et al.
phylaxis in 5 (13.5%) patients, and we kept the seizure
under control in all these patients by single dose
diazepam (10 mg).
In women developing eclampsia, detachment, DIC,
HELLP, cerebral hemorrhage and maternal mortality
risk increased.[4] The risk of HELLP syndrome is
reported about 10–15% in eclamptic cases.[3] However,
in recent publications in our country, the rate of
eclamptic patients developing HELLP syndrome
reached up to 40% and the eclampsia was grouped in
two categories as developing HELLP and not developing HELLP.[10,11,19] In line with the literature, HELLP
syndrome was the most common complication in our
patients while one patient had DIC, one patient had
renal failure following detachment and one patient had
sudden temporary loss of vision. Also, our patient
developing HELLP died after intracranial hemorrhage
on postpartum 10th day in the intense care unit of a
multidisciplinary hospital.
In the study investigating maternal death of 174
cases, Akar et al. found maternal mortality rate as
40/100,000 and preeclampsia- and eclampsia-induced
complications as the most common direct maternal
death.[20] It is reported in the world that eclampsiainduced maternal mortality rates has increased up to
15%.[5] Eclamptic cases are more common in developing countries and it is explained by the multiple numbers of convulsions occurring out of hospital and nonpresence of antenatal follow-ups of these cases. In our
country, maternal mortality rate in eclamptic cases is
reported between 0 and 14.6%.[21] In our study, we
found eclampsia-induced maternal mortality rate as
2.7% (1 case).
Perinatal morbidity and mortality rates are high in
the babies of eclamptic mothers. Preeclampsia and
eclampsia are responsible for 2.7% of perinatal mortality independent from prematurity and IUGR,
preeclampsia rate is 12% in newborns with IUGR and
19% in preterm newborns.[22] In a multinational study
supported by WHO and involved 29 countries, perinatal mortality rates were found as 2.6%, 9.2% and 22.6%
in non-preeclamptic/non-eclamptic, preeclamptic and
eclamptic pregnant women, respectively.[23] These complications are most likely prematurity-induced RDS,
apnea, jaundice, kernicterus, malnutrition, hypoglycemia, seizure, periventricular leukomalacia and prolonged hospitalization periods.[24,25] While most of our
24
Perinatal Journal
cases (61.1%) were born as premature, 12 (32.4%) cases
had IUGR. One case died during perinatal period and 4
cases during neonatal period. We found perinatal mortality rate as 12.5%.
Conclusion
In conclusion, severe preeclampsia and eclampsia are
significant reasons for maternal and perinatal morbidity and mortality in the world. Understanding the
pathophysiology better, close antenatal follow-ups and
appropriate treatment by hospitalizing risky cases in
tertiary healthcare centers with proper conditions may
decrease eclampsia incidence and associated secondary
maternal and perinatal morbidity and mortality rates.
Conflicts of Interest: No conflicts declared.
References
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5. Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Semin Perinatol 2012;36:56–9.
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ML, Surita FG, et al. The burden of eclampsia: results from
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7. Sibai BM. Eclampsia. VI. Maternal-perinatal outcome in 254
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olgunun de¤erlendirilmesi. Perinatoloji Dergisi 2007;15:61–7.
11. As›c›oglu O, Güngördük K, Yildirim G, Aslan H, Günay T.
Maternal and perinatal outcomes of eclampsia with and
without HELLP syndrome in a teaching hospital in western
Turkey. J Obstet Gynaecol 2014;34:326–31.
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12. Sumnulu I, ‹ldeniz M, Özel N. The incidence of pregnancy
induced hypertension in southeast Turkey. Int J Gynaecol
Obstet 1989;28:211–5.
13. ‹ngec M, Kumtepe Y, Borekci B, Bebek Z, Kadanal› S.
2001–2003 y›llar›ndaki 81 eklampsi olgusunun maternal ve
perinatal sonuclar›. Jinekoloji ve Obstetik Dergisi 2005;19:
135–41.
14. Liu S, Joseph KS, Liston RM, Bartholomew S, Walker M,
León JA, et al.; Maternal Health Study Group of Canadian
Perinatal Surveillance System (Public Health Agency of
Canada). Incidence, risk factors, and associated complications of eclampsia. Obstet Gynecol 2011;118:987–94.
15. Coghill AE, Hansen S, Littman AJ. Risk factors for eclampsia: a population-based study in Washington State, 19872007. Am J Obstet Gynecol 2011;205:553.e1–7.
16. Lopez-Llera M. Main clinical subtypes of eclampsia. Am J
Obstet Gynecol 1992;166:4–9.
17. Witlin AG, Sibai BM. Magnesium sulfate therapy in
preeclampsia and eclampsia. Obstet Gyencol 1998;92:883–9.
18. Hall DR, Odendaal HJ, Smith M. Is the prophylactic administration of magnesium sulphate in women with pre-eclampsia indicated prior to labor? BJOG 2000;107:903–8.
19. Kumtepe Y, Dündar O, Cetinkaya K, Ingeç M. Preeclampsia
and eclampsia incidence in the eastern anatolia region of
Turkey: the effects of high altitude. J Turk Ger Gynecol Assoc
2011;12:26–30.
20. Akar ME, Eyi EG, Yilmaz ES, Yuksel B, Yilmaz Z. Maternal
deaths and their causes in Ankara, Turkey, 1982–2001. J
Health Popul Nutr 2004;22:420–8.
21. Erden AC, Yayla M. Preeklampsi ve eklampside maternal ve
fetal morbidite-mortalite. Perinatoloji Dergisi 1993;1:24–30.
22. Dodd JM, O’Brien C, Grivell RM. Preventing pre-eclampsia – are dietary factors the key? BMC Med 2014;12:176.
23. Abalos E, Cuesta C, Carroli G, Qureshi Z, Widmer M, Vogel
JP, et al.; WHO Multicountry Survey on Maternal and
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Original Article
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Perinatal Journal 2015;23(1):26–29
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Factors affecting postpartum
depression in Diyarbak›r
Ali Emre Tahao¤lu1, Cihan To¤rul1, Mehmet ‹rfan Külahç›o¤lu1, Beflire Ayd›n Öztürk1, Deniz Balsak1,
Hanifi Bademk›ran1, Erdo¤an Gül1, Ümit Görkem2, Tayfun Güngör2
1
Gynecology & Obstetrics Clinic, Diyarbak›r Maternity and Pediatrics Hospital, Diyarbak›r, Turkey
2
Department of Gynecology & Obstetrics, Hitit University, Çorum, Turkey
Abstract
Özet: Diyarbak›r'da postpartum depresyonu
etkileyen faktörler
Objective: The aim of this study is to investigate the factors affecting postpartum depression (PPD) according to age groups in
Diyarbak›r city located on the southeastern part of Turkey.
Amaç: Bu çal›flman›n amac› Türkiye’nin güneydo¤usunda yer alan
Diyarbak›r ilinde postpartum depresyonu (PPD) etkileyen faktörleri yafl gruplar›na göre incelemektir.
Methods: The questions of Edinburgh postpartum depression scale
(EPDS) were asked to 495 women who referred to our clinic at their
postpartum periods. A separate statistical analysis was carried out for
51 adolescent women (below 18-year-old) and 72 puerperant
women over 35-year-old. Score 13 according to EPDS score result
was determined as cut-off value.
Yöntem: Klini¤imize baflvuran 495 postpartum dönemdeki kad›na Edinburgh postpartum depresyon skoru (EPDS) anket sorular›
soruldu. Elli bir adölesan (18 yafl alt›) ve 35 yafl üstü olan 72 lohusa için ayr› istatistiksel inceleme yap›ld›. EPDS skor sonucuna göre 13 puan cut-off de¤er olarak belirlendi.
Results: In 101 out of 495 (20.4%) patients, EPDS score was 13 and
above. This rate was 27.4% in adolescent puerperant women, and
19.4% in puerperant women over 35-year-old. It was found that
depression history was a significant variable affecting postpartum
depression (p<0.005).
Conclusion: Postpartum depression is a significant disease possible
to overlook which affects the health of mother and baby. This is
risky especially during adolescent period. Depression history is an
important variable in the etiology of postpartum depression. This
period can be screened for postpartum depression. The greatest factor limiting postpartum depression in Southeastern Anatolia Region
which has the highest reproduction rate in Turkey can be the support provided to the puerperant women by relatives and friends during puerperal period.
Keywords: Postpartum period, postpartum depression.
Introduction
Gestation is a period when a woman has her physiological, psychological and social changes. Prenatal and post-
Bulgular: Toplam 495 hastan›n 101’inde (%20.4) EPDS skoru 13
ve üzerinde idi. Adölesan lohusalarda bu oran %27.4, 35 yafl üstü
lohusalarda ise %19.4 idi. Geçirilmifl depresyon öyküsünün postpartum depresyonu etkileyen anlaml› bir de¤iflken oldu¤u bulundu (p<0.005).
Sonuç: Postpartum depresyon anne ve çocuk sa¤l›¤›n› etkileyen
önemli ve gözden kaç›r›lmas› olas› bir hastal›kt›r. Bu durum özellikle adölesan ça¤da risklidir. Geçirilmifl depresyon hikayesi postpartum depresyon etyolojisinde en önemli de¤iflkendir. Postpartum depresyon için bu dönemde tarama yap›labilir. Türkiye’nin en
yüksek üreme h›z›na sahip olan Güneydo¤u Anadolu bölgesinde
postpartum depresyonu s›n›rlayan en büyük etken akraba ve arkadafl çevresinin puerperal dönemde lohusalara verdi¤i destek olabilir.
Anahtar sözcükler: Postpartum dönem, postpartum depresyon.
natal changes, newborn care, breast feeding problems,
new environment, and changes in social status may cause
the health of pregnant woman to deteriorate. A peak in
Correspondence: Ali Emre Tahao¤lu, MD. Diyarbak›r Kad›n Do¤um ve Çocuk Hastal›klar›
Hastanesi Kad›n Hast. ve Do¤um Klini¤i, Diyarbak›r, Turkey. e-mail: alyemre@yahoo.com
Received: April 23, 2014; Accepted: January 5, 2015
Please cite this article as: Tahao¤lu AE, To¤rul C, Külahç›o¤lu M‹, Ayd›n Öztürk B,
Balsak D, Bademk›ran H, Gül E, Görkem Ü, Güngör T. Factors affecting postpartum
depression in Diyarbak›r. Perinatal Journal 2015;23(1):26–29.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231006
doi:10.2399/prn.15.0231006
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Factors affecting postpartum depression in Diyarbak›r
the depression rate was reported at postpartum fourth
and eighth weeks.[1] In a meta-analysis, it was reported
that postpartum depression rate in the first three postpartum months was 14.5%, and major depression criteria were satisfactorily met in 6.5% of postpartum
women, and this was at higher levels especially in nullipara population.[1] Changes during pregnancy may bring
along many problems and cause stress.[2] The period
after pregnancy is 3–4 times more risky in terms of mental illnesses than gestational period.[3] Therefore, possible postpartum depression may constitute a significant
health problem.
According to Diagnostic and Statistical Manual of
Mental Disorders (DSM), having 5 or more of the criteria for at least two weeks is defined as postpartum
depression (PPD). These are insomnia-hypersomnia,
psychomotor agitation or retardation, fatigue, unhappiness or sense of guilt, decreased concentration, changes
in appetite and suicide ideation. These episodes begin
within postpartum four weeks and ends within 1 year.
According to DSM, PPD is described as non-psychotic
major depression.[4]
Identifying and preventing postpartum depression in
advance is significant in terms of the health of baby and
mother. Edinburgh Postpartum Depression Scale
(EPDS) can be used to investigate postpartum depression.[5] Although this scale is not diagnostic, sensitivity of
PPD is 61.5% and specificity of PPD is 77.4% for those
scoring 13 and above.[6]
where each option is scored between 0 and 3 and maximum total score is 30.[6]
The study was separated into 3 groups according to
the age groups which are adolescents, puerperant
women who are over 35-year-old and all puerperant
women. Statistical analysis was performed by SPSS
15.0 (SPSS Inc., Chicago, IL, USA) and definitive statistics and chi-square test were used.
Results
The factors affecting postpartum depression were investigated by categorizing 495 puerperant women in the
study according to their age groups, which were adolescent puerperant women and puerperant women over 35year-old. As risk factors, their ages, number of their living children, financial status, educational status, delivery
type, if they had any emesis problem, gender of baby,
depression history and if the pregnancy was intended
were asked. Among all the age groups, it was found that
only depression history affected PPD (p<0.001).
In 101 out of 495 (20.4%) patients, EPDS score was
13 and above. In the factors investigated, it was found
that only the depression history was a significant factor
affecting postpartum depression in puerperant women
(Table 1).
Table 1. Statistical analysis of 495 patients.
No depression Depression exists
(n=394)
(n=101)
Methods
Our study was carried out on 495 puerperant women
who referred to Diyarbak›r Maternity and Pediatrics
Hospital between September 2012 and May 2013. The
approval of the Ethics Committee of Okmeydan›
Training and Research Hospital was obtained. Patient
consent forms were received from all participants.
Women who delivered term babies (at 37 weeks and
above) were included in the study. The exclusion criteria included multiple pregnancy, pregnancy by assisted
reproductive techniques, history of mental disease
diagnosis, antenatal fetal anomaly and mother or baby
being in the intense care unit.
All puerperant women included in the study on
postpartum 8 weeks were asked EPDS questions and
factors that may affect postpartum depression. EPDS is
a questionnaire with 10 items, each having 4 options
p
value
Age
Mean: 26.7±6.6 (14–52)
26.7±6.5
26.5±7.1
0.7540
Number of living children
2.2 (0–10)
3.8 (0–11)
0.115
Financial status
600 TL and below
600–1500 TL
1500–5000 TL
78.4
19.3
2.3
72.3
22.8
5
0.162
Educational level
Illiterate
Literate
Primary school
Secondary school
High school
University
36.3
23.4
23.9
7.1
6.6
2.8
35.6
23.8
19.8
9.9
5.9
5
0.718
Delivery type (C/S)
207
54
0.602
Emesis (present)
64
17
0.887
Depression history (exists)
6
16
<0.001
Gender of baby (male)
198
55
0.452
Planned pregnancy (exists)
41
14
0.325
Volume 23 | Issue 1 | April 2015
27
Tahao¤lu AE et al.
It was seen in 495 patients who were analyzed that
age, number of living children, educational status,
financial status, delivery type, emesis problem, if the
pregnancy was intended or not and gender of baby
were not significant factors in terms of postpartum
depression.
Postpartum depression was identified in 51
patients, of which 14 cases (27.4%) were adolescent
puerperant women below 18-year-old (Table 2). None
of the factors analyzed had a significant effect on postpartum depression.
Postpartum depression was identified in 14 (19.4%)
out of 72 patients who were puerperant women above
35-year-old (Table 3). None of the factors had any
effect on postpartum depression.
Discussion
Even though the pregnancy and delivery are physiological, they may affect the health of mother and baby
in a negative way. While most of the women can adapted to physiological, psychological and social changes
occurring during pregnancy and delivery, some women
may suffer mental illnesses at different levels.[7] It has
been shown that PPD constitutes a risk in motherinfant relationship, and affects cognitive and emotional development of baby.[8] Verbal and visual communication problems of baby and disorders in emotional,
cognitive, verbal and social abilities are the negative
effects of PPD.[9]
In our study, we found that number of living children, financial status, educational level, delivery type,
presence of emesis during pregnancy, whether pregnancy being intended or not and gender of baby did
not affect postpartum depression. It was observed that
only depression history affected postpartum depression. It has been already shown in many studies that
depression history is a significant factor affecting postpartum depression.[10,11]
In our study, we found that the rate of postpartum
depression at postpartum 8 weeks in Diyarbak›r city
and nearby regions was 20.4% (according to EPDS,
cut-off was 13 and above). The study carried out in
Trabzon found PPD rate as 28.1%.[12] However, other
studies performed in Turkey found PPD rate as
14.0%, 16.8% and 14.0%, respectively.[11,13,14] We found
PPD rate during adolescent period as 27.4% which was
the highest result among the age groups. There are
28
Perinatal Journal
Table 2. Statistical analysis of puerperant women below 18-year-old.
No depression Depression exists
(n=37)
(n=14)
Number of living children
p
value
1
1
0.079
Financial status
600 TL and below
600–1500 TL
1500–5000 TL
64.9
35.1
-
50
50
-
0.337
Educational level
Illiterate
Literate
Primary school
Secondary school
High school
University
35.1
16.2
16.2
16.2
13.5
2.2
28.6
28.6
14.3
21.4
7.1
-
0.871
Delivery type (C/S)
26
7
0.176
Emesis (present)
5
1
1.000
Depression history (exists)
1
0
1.000
Gender of baby (male)
20
8
0.843
Planned pregnancy (exists)
1
2
0.179
contradictory results among age groups for PPD.
Some studies found that being below 25-year-old is a
significant factor for PPD.[15,16] Some other studies
showed that postpartum depression presented no difference among age groups.[17]
The prevalence of postpartum depression during
the test period may differ according to population size,
Table 3. Statistical analysis of puerperant women above 35-year-old.
No depression Depression exists
(n=58)
(n=14)
Number of living children
p
value
5 (0–10)
5 (0–11)
0.835
Financial status
600 TL and below
600–1500 TL
1500–5000 TL
77.6
17.2
5.2
78.6
14.3
7.1
0.969
Educational level
Illiterate
Literate
Primary school
Secondary school
High school
University
44.8
10.3
20.7
12.1
5.2
6.9
50
14.3
28.6
7.1
0.460
Delivery type (C/S)
20
3
0.525
Emesis (present)
7
4
0.207
Depression history (exists)
2
2
0.168
Gender of baby (male)
34
11
0.166
Planned pregnancy (exists)
3
0
1.000
Factors affecting postpartum depression in Diyarbak›r
study design, test type and cut-off value. Mostly, the
negative results of this situation which cannot be
detected by healthcare professionals on health of
mother and baby should be known and it should be on
the alert against this mood disorder in puerperant
women especially with depression history.
Routine screening is performed for postpartum
depression diagnosis in some countries such as
Australia and the USA.[18] Such screening procedures
may also be helpful in Turkey to detect such a complicated condition for baby and mother.
The depression rate is correlated with other regions
in Anatolia region which has the highest fertility rate in
Turkey, and in Diyarbak›r which on the 10th rank for
fertility rate.[19] The reason for this situation can be
explained with the support from relatives and friends
during postpartum period.
Conclusion
Although postpartum depression is usually overlooked,
it is a significant mood disorder, which should be diagnosed and treated, and it affects maternal health and
development of baby.
Conflicts of Interest: No conflicts declared.
References
6. Aydin N, Inandi T, Yigit A, Hodoglugil NN. Validation of
the Turkish version of the Edinburgh Postnatal Depression
Scale among women within their first postpartum year. Soc
Psychiatry Psychiatr Epidemiol 2004;39:483–6.
7. Gülseren L. Do¤um sonras› depresyon: Bir gözden geçirme.
Turk Psikiyatri Derg 1999;10:58–67.
8. Murray L, Cooper PJ. Effects of postnatal depression on
infant development. Arch Dis Child 1997;77:99–101.
9. Brand SR, Brennan PA. Impact of antenatal and postpartum
maternal mental illness: how are the children? Clin Obstet
Gynecol 2009;52:441–55.
10. Gonidakis F, Rabavilas AD, Varsou E, Kreatsas G,
Christodoulou GN. A 6-month study of postpartum depression and related factors in Athens Greece. Compr Psychiatry
2008;49:275–82.
11. Kirpinar I, Gözüm S, Pasinlio¤lu T. Prospective study of
postpartum depression in eastern Turkey prevalence, sociodemographic and obstetric correlates, prenatal anxiety and
early awareness. J Clin Nurs 2010;19:422–31.
12. Ayvaz S, Hocao¤lu C, Tiryaki A, Ak I. Incidence of postpartum depression in Trabzon province and risk factors at gestation. [Article in Turkish] Turk Psikiyatri Derg 2006;17:
243–51.
13. Danaci EA, Dinç G, Deveci A, Sen FS, Içelli I. Postnatal
depression in Turkey: epidemiological and cultural aspects.
Soc Psychiatry Psychiatr Epidemiol 2002;37:125–9.
14. Gulseren L, Erol A, Gulseren S, Kuey L, Kilic B, Ergor G.
From antepartum to postpartum: a prospective study on the
prevalence of peripartum depression in a semiurban Turkish
community. J Reprod Med 2006;51:955–60.
1. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S,
Gartlehner G, Swinson T. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol 2005;
106:1071–83.
15. Lanes A, Kuk JL, Tamim H. Prevalence and characteristics
of postpartum depression symptomatology among Canadian
women: a cross-sectional study. BMC Public Health
2011;11:302.
2. Okanl› A, Tortumo¤lu G, K›rp›nar ‹. Gebe kad›nlar›n
ailelerinden alg›lad›klar› sosyal destek ile problem çözme
becerileri aras›ndaki iliflki. Anadolu Psikiyatri Dergisi 2003;
4:98–105.
16. Inandi T, Elci OC, Ozturk A, Egri M, Polat A, Sahin TK.
Risk factors for depression in postnatal first year, in eastern
Turkey. Inter J Epidemiol 2002;31:1201–7.
3. Deveci, A. Postpartum psikiyatrik bozukluklar. Birinci
Basamak için Psikiyatri 2003;2:42–6.
17. Goker A, Yan›kkerem E, Demet MM, Dikayak S, Yildirim
Y, Koyuncu FM. Postpartum depression: is mode of delivery
a risk factor? ISRN Obstet Gynecol 2012;2012:616759.
4. American Psychological Association. Diagnostic and Statistical
Manual of Mental Disorders. DSM-IV-tr. 4th ed. Washington
DC: American Psychiatric Association; 2000.
5. Cox JL, Holden JM, Sagovsky R. Detection of postnatal
depression. Development of the 10-item Edinburgh Postnatal
Depression Scale. Br J Psychiatry 1987;150:782–6.
18. Hübner-Liebermann B, Hausner H, Wittmann M.
Recognizing and treating peripartum depression. Dtsch
Arztebl Int 2012;109:419–24.
19. Türkiye ‹statistik Kurumu (TÜ‹K). Do¤um ‹statistikleri,
2012. Ankara: TÜ‹K; 2013; Nr. 13618.
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Original Article
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Perinatal Journal 2015;23(1):30–33
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Analysis of maternal serum and urinary
lipocalin-2 levels
Yeflim Bayo¤lu Tekin1, Ülkü Mete Ural1, Aynur K›rbafl2, fienol fientürk1, Figen K›r fiahin1
1
Department of Obstetrics & Gyneceology, Faculty of Medicine, Recep Tayyip Erdo¤an University, Rize, Turkey
2
Department of Biochemistry, Faculty of Medicine, Recep Tayyip Erdo¤an University, Rize, Turkey
Abstract
Özet: Maternal serum ve üriner lipokalin-2
düzeylerinin de¤erlendirilmesi
Objective: Lipocalin-2 is a glicoprotein secreted by leukocytes. It is
known that lipocalin-2 levels are affected in maternal blood and
urine depending on the endothelial damage induced by preeclampsia, and hyperglycemia created by gestational diabetes. However,
there are not sufficient studies investigating the levels in healthy
pregnants. In our study, we aimed to determine the changes in
lipocalin-2 levels of healthy pregnant women.
Amaç: Lipokalin-2 lökositlerden salg›lanan bir glikoproteindir.
Preeklampsinin indükledi¤i endotel hasar›na ve gestasyonel diyabetin oluflturdu¤u hiperglisemiye ba¤l› olarak maternal kanda ve
idrarda lipokalin-2 düzeylerinin etkilendi¤i bilinmektedir. Ancak
sa¤l›kl› gebelerdeki düzeylerini araflt›ran yeterli say›da çal›flma bulunmamaktad›r. Bu çal›flmada sa¤l›kl› gebelerde lipokalin-2 düzeylerindeki de¤iflikliklerin belirlenmesi amaçlanm›flt›r.
Methods: This study was carried out as cross-sectional and casecontrolled. Lipocalin-2 levels were determined in blood and urine
at first and third trimesters in the same patient group and they were
compared. Also, full blood parameters, biochemical and urinary
data of the cases were also evaluated.
Yöntem: Bu çal›flma kesitsel ve vaka kontrollü olarak yürütülmüfltür. Ayn› hasta grubundan ilk ve üçüncü trimesterde kan ve idrarda lipokalin-2 düzeyleri belirlenerek karfl›laflt›r›lm›flt›r. Ayr›ca olgular›n tam kan parametreleri, biyokimyasal ve üriner verileri de
de¤erlendirilmifltir.
Results: Lipocalin-2 levels decrease at a statistically significant level
in both maternal blood and urine at the third trimester (p<0.05).
However, no significant change was found in other hematologic,
biochemical and urinary parameters (p>0.05).
Bulgular: Lipokalin-2 düzeyleri hem maternal kanda hem de idrarda üçüncü trimesterde istatistiksel olarak anlaml› düzeyde düflmektedir (p<0.05). Ancak di¤er hematolojik, biyokimyasal ve üriner parametrelerde anlaml› de¤ifliklik saptanmam›flt›r (p>0.05).
Conclusion: Lipocalin-2 is a new marker used in the early diagnosis
of gestational complications such as preeclampsia and gestational diabetes. It is seen that lipocalin-2 levels in healthy pregnant women
decrease to lower levels in third trimester compared to first trimester.
However, further studies are required with more populations where
maternal serum and urine levels are determined longitudinally.
Sonuç: Lipokalin-2 preeklampsi ve gestasyonel diyabet gibi gebelik komplikasyonlar›n›n erken tan›s›nda kullan›lan yeni bir markerdir. Sa¤l›kl› gebeliklerde lipokalin-2 seviyelerinin ilk trimestere göre 3. trimesterde daha düflük seviyelere indi¤i görülmektedir.
Ancak daha genifl olgu serileri ile longitudinal olarak maternal serum ve idrar düzeylerinin belirlendi¤i çal›flmalara ihtiyaç vard›r.
Keywords: Pregnancy, lipocalin-2, biochemical marker.
Anahtar sözcükler: Gebelik, lipokalin-2, biyokimyasal marker.
Introduction
Lipocalin-2 is a glycoprotein weighing 25 kDa from
lipocalin family. It was first defined as a matrix protein in
granules within human neutronphiles.[1] In different cell
types, it has a role as a growth and differentiation factor.
Its expression was found in many organs such as liver,
kidney and adipose tissue. It was shown that it is also
secreted at higher rates in also inflammatory reactions.[2]
It has been determined that lipocalin-2 is an inflammatory marker closely associated with insulin resistance
and hyperglycemia, and has a role to create insulin resist-
Correspondence: Yeflim Bayo¤lu Tekin, MD. Recep Tayyip Erdo¤an Üniversitesi
T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Rize, Turkey.
e-mail: yesimbay@yahoo.com
Received: October 4, 2014; Accepted: January 12, 2015
Please cite this article as: Bayo¤lu Tekin Y, Mete Ural Ü, K›rbafl A, fientürk fi, K›r fiahin F.
Analysis of maternal serum and urinary lipocalin-2 levels. Perinatal Journal 2015;23(1):30–33.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231007
doi:10.2399/prn.15.0231007
QR (Quick Response) Code:
Analysis of maternal serum and urinary lipocalin-2 levels
ance for gestational diabetes.[3] It was shown that it is
secreted from mature renal epithelium, and it is useful to
identify renal damage at early period. Also, it was found
that maternal lipocalin-2 levels increased at the early
period depending on the preeclampsia.[4]
Although lipocalin-2 levels were found to be high in
gestational complications such as preeclampsia and gestational diabetes in the literature, there are no sufficient
studies evaluating lipocalin-2 levels in normal pregnancies and changes during pregnancy. Our aim in this
study is to evaluate lipocalin-2 levels in healthy pregnant
women and to determine changes during pregnancy. In
this way, it would be more significant to understand if
the changes found in gestational complications are physiological responses or the results of the disease pathogenesis. In our study, we aimed to determine and compare lipocalin-2 values at first and third trimesters in
healthy pregnant women not complicated by any pregnancy-induced diseases, and to identify the changes in
lipocalin-2 levels during pregnancy.
Methods
This is a cross-sectional case-controlled study. The
study was carried out for a year in antenatal polyclinic of
a university hospital. The study was approved by the
local ethics committee of the university, and the consents of the participants were received by informing
them about the study.
Pregnant women between 18- and 35-year-old
referred to the hospital for their first antenatal visit were
included in the study. Patients with chronic hypertension, preeclampsia, pregestational diabetes history or
those diagnosed with gestational diabetes in their previous pregnancies were excluded from the study. Also the
patients with the history of renal, cardiovascular,
autoimmune and hepatobiliary system diseases were
excluded from the study.
First venous blood and urine samples were collected
from the patients who referred within their first
trimester during their 9–12 weeks of gestation and found
to have single alive fetus. Second blood and urine samples were collected at the visit carried out between 34
and 36 weeks of gestation. Blood and urine samples were
first centrifuged and then separated as supernatant, and
kept at -20°C. Full blood parameters and routine biochemical and urinary analyses of the participants were
done concurrently in order to determine possible additional pathologies and hematologic, biochemical and
urinary anomalies which may be induced by pregnancy.
Lipocalin-2 serum and urine levels were studied by
ELISA method and according to the recommendations
of Biovender (Research and Diagnostic Products,
Heidelberg, Germany). Intra-assay and inter-assay coefficients of variation (CV) were found as 7.5% and 9.7%.
Sensitivity was calculated as 0.02 ng/ml.
Statistical analysis was carried out by SPPS statistical
software (SPSS Inc., Chicago, IL, USA) version 17.0.
Normal distribution of the data was tested by
Kolmogorov-Smirnov test and Lilliefor’s correction test.
The data displaying normal distribution were provided as
mean±standard deviation. Paired-sample test was used to
compare first and second blood and urine samples. The
value p<0.05 was considered statistically significant.
Results
Forty healthy pregnant women who referred in their first
trimester were included in the study. Five of the cases did
not come for their visits. Two cases were excluded from
the study due to gestational diabetes and one case due to
preeclampsia. The study was completed with a total of 32
cases. Mean age of the participants was 28.9±5.6 and the
gravida was 2.0±1.1. Maternal hematologic, biochemical
and urinary parameters of first and third trimesters were
compared. In both visits, no significant difference was
found in hemoglobin, hematocrit and platelet values
from full blood parameters and in glucose, BUN, creatinine, ALT, AST and urinary pH and density values from
biochemical parameters (Table 1). It was seen that both
Table 1. Comparison of maternal serum and urinary parameters
according to the trimesters.
s-lipocalin-2 (ng/ml)
u-lipocalin-2 (ng/ml)
Glucose (mg/dL)
Creatinine (mg/dL)
BUN (mg/dL)
ALT (U/L)
AST (U/L)
WBC (K/uL)
Hb (g/dL)
Hct (%)
PLT (K/uL)
u-pH
Density
First trimester
Last trimester
P value
78.79±20.4
76.84±62.50
90.84±13.29
0.57±0.07
14.36±4.02
11.45±4.86
14.62±3.15
10.93±1.68
11.3±1.08
33.20±2.48
236.91±61.74
6.37±0.76
1.012±0.004
60.48±20.69
36.34±29.79
92.15±13.07
0.57±0.06
14.8±3.4
11.33±3.96
14.70±2.86
9.94±1.48
11.58±1.33
33.96±2.43
233.47±60.25
6.14±0.56
1013±0.005
0.001
0.022
0.837
0.705
0.530
0.893
0.711
0.053
0.083
0.172
0.431
0.217
0.507
ALT: alanine transaminase; AST: aspartate transaminase; BUN: blood urea nitrogen;
Hb: hemoglobin; Hct: hematocrit; PLT: platelet; s-: serum; u-: urinary; WBC: white
blood cell.
Volume 23 | Issue 1 | April 2015
31
Bayo¤lu Tekin Y et al.
urinary and serum lipocalin-2 levels were significantly
low in the third trimester compared to the first trimester
(Table 1).
Discussion
In our study, we evaluated maternal serum and urinary
lipocalin-2 levels in the first and third trimesters of
non-complicated pregnant women, and we found that
lipocalin levels of both in urine and serum were significantly lower in the third trimester. In their study,
Edelstam et al. evaluated lipocalin-2 levels on healthy
pregnant women during the third trimester at 33, 36
and 39 weeks of gestation and postpartum period.
They reported that lipocalin-2 levels increased
depending on the week of gestation; however, these
levels reached their highest values at postpartum period.[5] They stated that increasing lipocalin-2 levels may
be associated with postpartum infection.
Lipocalin-2 levels are usually the discussion topic of
the studies carried out on complicated pregnancies. As
being a marker to determine endothelial damage, they
are used in studies on preeclampsia.[6] The lipocalin-2
values in pregnant women complicated with
preeclampsia were reported at higher levels. It was
even shown that this increase induced by endothelial
damage began in the second trimester and continued
to increase on the third trimester. In these studies
where healthy pregnant women were included as control group, it was stated that lipocalin-2 levels were stable in healthy cases.[6] Similarly, Karampas et al. found
in their longitudinal studies where healthy pregnant
women were compared with pregnant women complicated with preeclampsia and growth retardation that
lipocalin-2 levels were similar to normal pregnant
women in all three trimesters.[7] Ödum et al. reported
that lipocalin-2 in the urine were at high levels in normal pregnant women unlike preeclampsia.[8] However,
we observed in our study that lipocalin-2 levels were
not stable in normal pregnant women, and they were
significantly low both in urine and serum in the third
trimester compared to the first trimester.
In a study performed on 130 healthy individuals
where lipocalin-2 was used to determine renal function
and glomerular filtration, serum lipocalin-2 levels of
non-pregnant women were compared with the values
at all three trimesters of gestation. However, this was
not a case-controlled study, and the values at the second trimester were high significantly.[9]
32
Perinatal Journal
The strength of our study is to be a case-controlled
study. Analysis of lipocalin-2 levels of the same patient
group in urine and serum at both first and third
trimesters, and significantly low results obtained in
both analyses show the reliability of the study.
However, small number of population, cases being
preconceptional, and non-availability of second
trimester and postpartum values are among the limitations of the study.
Conclusion
Lipocalin-2 is a promising marker as the early identifier of endothelial damage, and for the early diagnosis of
preeclampsia as well as glucose intolerance and hyperglycemia. However, in the light of existing studies, it
raises concern that lipocalin-2 levels in healthy pregnant women do not have clear standard ranges, and
there are contradictory results about the progress of
blood and urine levels during pregnancy. The results
of our study contribute to the determination of the
normal progress of lipocalin-2 in healthy pregnant
women as a candidate marker to predict severe gestational complications. On the other hand, further studies with wider populations where reference ranges are
determined well according to the trimesters in healthy
pregnant women will help to enhance the diagnostic
capabilities of lipocalin-2.
Conflicts of Interest: No conflicts declared.
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Buemi M. Second trimester neutrophil gelatinase-associated
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Acta Obstet Gynecol Scand 2008;87:1370–3.
Analysis of maternal serum and urinary lipocalin-2 levels
5. Edelstam G, Löwbeer C, Kral G, Gustafsson SA, Venge P.
New reference values for routine blood samples and human
neutrophilic lipocalin during third-trimester pregnancy.
Scand J Clin Lab Invest 2001;61:583–92.
metalloproteinase-9 (MMP-9) and their complex MMP9/NGAL in pregnancies with preeclampsia and those with a
small for gestational age neonate: a longitudinal study.
Prenat Diagn 2014;34:726–33.
6. D’Anna R, Baviera G, Giordano D, Todarello G, Russo S,
Recupero S, et al. Neutrophil gelatinase-associated lipocalin
serum evaluation through normal pregnancy and in pregnancies complicated by preeclampsia. Acta Obstet Gynecol
Scand 2010;89:275–8.
8. Ødum L, Andersen AS, Hviid TV. Urinary neutrophil
gelatinase-associated lipocalin (NGAL) excretion increases
in normal pregnancy but not in preeclampsia. Clin Chem
Lab Med 2014;52:221–5.
7. Karampas G, Eleftheriades M, Panoulis K, Rizou M,
Haliassos A, Hassiakos D, et al. Maternal serum levels of
neutrophil gelatinase-associated lipocalin (NGAL), matrix
9. Ma∏yszko JS, Rams L, Drozdowska-Rams L, Ma∏yszko J.
Serum neutrophil gelatinase-associated lipocalin as a marker
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Med Sci 2010;6:744–7.
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Critical pulmonary stenosis with prenatal diagnosis:
a case series and review of literature
Oya Demirci1, Taner Yavuz2, Resul Ar›soy1, Emre Erdo¤du1, P›nar Kumru1, Oya Pekin1
1
Perinatology Clinic, Zeynep Kamil Maternity and Pediatrics Training and Research Hospital, Istanbul, Turkey
Pediatric Cardiology Unit, Zeynep Kamil Maternity and Pediatrics Training and Research Hospital, Istanbul, Turkey
2
Abstract
Özet: Prenatal tan›l› kritik pulmoner stenoz:
Olgu serisi ve literatür derlemesi
Objective: The aim of the study is to investigate the morphology of
right ventricular cavity, the tricuspid valve size and the treatments
applied at postnatal period in cases with critical pulmonary stenosis
(PS) having intact ventricular septum.
Amaç: Ventriküler septumu intakt olan kritik pulmoner stenozlu
(PS) olgularda sa¤ ventrikül kavitesinin morfolojisi, triküspit kapak
boyutu ve postnatal uygulanan tedavilerin de¤erlendirilmesi amaçlanm›flt›r.
Methods: Seven cases included in the study who were considered to
have critical PS in fetal echocardiography at second and third
trimesters. The fetuses found to have antegrade jet stream at pulmonary valve level and reverse flow at ductus arteriosus as well as
hyperthrophy and hypoplasia on the right ventricle were determined
as critical PS. The cases were categorized as bipartite or tripartite
according to the morphology of right ventricular cavity. Z-score of
tricuspid valve was calculated according to the week of gestation.
Yöntem: Çal›flmaya ikinci ve üçüncü trimestrede fetal ekokardiyografide kritik PS düflünülen 7 olgu al›nd›. Sa¤ ventrikülde hipertrofi ve hipoplazinin yan› s›ra pulmoner kapak seviyesinde ileri
yönde jet ak›m ve duktus arteriozusta ters ak›m saptanan fetüsler
kritik PS olarak de¤erlendirildi. Sa¤ ventrikül kavitesinin morfolojisine göre olgular bipartit veya tripartit olarak ayr›ld›. Gestasyon
haftas›na göre triküspit kapak Z-skoru hesapland›.
Results: Bipartite right ventricle cavity was found in cases diagnosed at second trimester, and tripartite right ventricle cavity in
cases diagnosed at third trimester. Tricuspid valve Z-score of the
cases with bipartite right ventricle morphology was less than those
with tripartite. Two out of seven cases were monochorionic diamniotic twin pregnancies. Balloon valvuloplasty was performed on postnatal second day despite the prostaglandin E1 (PGE1) infusion in 3
cases with bipartite, and 3 cases required Blalock-Taussing shunt. In
four tripartite cases, cyanosis control was better by PGE1 infusion,
and balloon valvuloplasty was performed on postnatal second day in
3 cases and on postnatal 55th day in 4 cases. No Blalock-Taussing
shunt was required.
Conclusion: In critical PS cases, the treatment methods to be
applied during postnatal period may vary according to the right ventricle being of two or three parts and the stenosis level of tricuspid
valve.
Keywords: Critical pulmonary stenosis, tricuspid stenosis, tricuspid
deficiency, postnatal treatment.
Bulgular: ‹kinci trimesterde tan› konulan olgularda bipartit,
üçüncü trimesterde tan› konulan olgularda tripartit sa¤ ventrikül
kavitesi belirlendi. Bipartit sa¤ ventrikül morfolojili olgular›n triküspit kapak Z-skoru, tripartit olanlardan daha düflük olarak hesapland›. Yedi olgunun ikisi monokoryonik diamniyotik ikiz gebelikti. Bipartit olan 3 olguda prostaglandin E1 (PGE1) infüzyonuna
ra¤men postnatal 2. günde balon valvüloplasti yap›ld› ve 3 olguda
da Blalock-Taussing flant gereksinimi oldu. Tripartit dört olguda
ise PGE1 infüzyonu ile siyanoz kontrolü daha iyi sa¤lanm›fl, üç olguda postnatal 2. haftada, dördüncü olguda ise postnatal 55. günde balon valvüloplasti uyguland›. Blalock-Taussing flant gereksinimi olmad›.
Sonuç: Kritik PS olgular›nda sa¤ ventrikülün iki ya da üç parçal›
olma durumuna, triküspit kapa¤›n darl›k derecesine ba¤l› olarak
postnatal dönemdeki uygulanacak tedavi yöntemleri de¤iflebilmektedir.
Anahtar sözcükler: Kritik pulmoner stenoz, triküspit darl›k, triküspit yetmezlik, postnatal tedavi.
Correspondence: Oya Demirci, MD. Zeynep Kamil Kad›n ve Çocuk Hastal›klar› E¤itim ve
Araflt›rma Hastanesi, Perinatoloji Klini¤i, ‹stanbul, Turkey. e-mail: demircioya@gmail.com
Received: October 27, 2014; Accepted: January 24, 2015
Please cite this article as: Demirci O, Yavuz T, Ar›soy R, Erdo¤du E, Kumru P,
Pekin O. Critical pulmonary stenosis with prenatal diagnosis: a case series and review
of literature. Perinatal Journal 2015;23(1):34–38.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231008
doi:10.2399/prn.15.0231008
QR (Quick Response) Code:
Critical pulmonary stenosis with prenatal diagnosis
Introduction
Critical pulmonary stenosis (PS) causes reverse flow in
the ductus arteriosus of fetus and severe right ventricular
hypertrophy. Secondary to hypertrophy, the right ventricular cavity gets narrow especially at apex. During
neonatal period, it causes shunt and cyanosis at interatrial level from right to left. Critical PS can also be evaluated within pulmonary atresia with intact ventricular septum (PAIVS) due to the fact that it may progress to pulmonary atresia (PA) as week of gestation advances.[1] The
most distinguishing characteristic of the fetus with critical pulmonary stenosis from mild and medium PS is the
reverse flow of ductus arteriosus seen in ultrasonographic examination.[1,2] There is no concomitant genetic disease or extra cardiac anomaly in most of the PAIVS and
critical PS cases.[1] The abnormal appearance in
quadrilocular during cardiac examination between 18
and 22 weeks of gestation at second trimester is usually
the most striking characteristics and it initiates the
process toward the diagnosis. However, although some
cases have PS at critical levels, the sizes of right ventricle
may seem normal and it may cause late diagnosis. In
some other cases, PAIVS and critical PS diagnosis may
be established even at the first trimester.[1]
Right ventricular cavity morphologically consists of
three parts which are inlet, apex and outlet. Ventricular
hyperthropy occurs at various levels depending on the
size of narrowing of the right ventricular outlet and the
week of gestation that pulmonary atresia occurs, stenosis
on tricuspid valve and the level of failure.[1] As a result of
the overgrowth of intracavity muscular layer, apex of
right ventricle (bipartite) or both apex and outlet (unipartite) may not develop. In critical PS, right ventricle usually has all three parts (tripartite). Sometimes, apical
region may not develop well and may have bipartite morphology as in PAIVS.[1,2] Z-score is used when evaluating
tricuspid valve size.[1–3] In cases which developed right
ventricular hypoplasia with bipartite and unipartite morphology, severe tricuspid valve stenosis (low Z-score) is
also observed.[1,2]
For newborns with critical pulmonary stenosis, various treatment options are offered according to right ventricular morphology usually at postnatal early period
such as balloon valvuloplasty, ductal stent, BlalockTaussing (BT) shunt operation, biventricular repair at
advanced periods, and Glenn or Fontan procedures. In
our study, we aimed to investigate the morphology of
right ventricular cavity, tricuspid valve Z-scores and
treatments applied in cases with critical pulmonary
stenosis (PS) having intact ventricular septum.
Methods
Seven cases considered having critical PS in fetal
echocardiography at second and third trimesters at the
Perinatology Clinic of Zeynep Kamil Maternity and
Pediatrics Training and Research Hospital between
2013 and 2014 were included in the study. The fetuses
found to have antegrade jet stream at pulmonary valve
level and reverse flow at ductus arteriosus as well as
hyperthrophy and hypoplasia on the right ventricle were
suspected to be critical PS. The cases with postnatal
clinical progress and echocardiography findings compatible with critical PS were included in the study. The
cases were categorized as bipartite or tripartite according to the morphology of right ventricular cavity. Zscore of tricuspid valve was calculated according to the
week of gestation.[3] Tricuspid valve insufficiency was
categorized as mild, medium and severe.[4,5]
Ultrasonographic examinations were performed with
the use of Voluson 730 Pro (GE Healthcare,
Milwaukee, WI, USA). Transthoracic echocardiography was carried out on the first day after the delivery.
Prenatal and postnatal echocardiography measurements
were evaluated by pediatric cardiology and perinatology
departments. Statistical analysis was done by SPSS v.
11.5 (SPSS, Inc., Chicago, IL, USA). Constant data
were provided as median.
Results
Median week of gestation for the cases was 32 (range:
24 to 34) weeks when prenatal diagnosis was established. In the fetal ultrasonography during second
trimester for the cases which were diagnosed at third
trimester, the size of right ventricle was normal, and no
abnormality was observed at the right ventricle outlet.
Bipartite right ventricle cavity was found in cases diagnosed at second trimester, and tripartite right ventricle
cavity in cases diagnosed at third trimester. No case
developed pulmonary atresia. Median delivery week
was 37 (range: 37 to 39 weeks) and median birth weight
was 2950 (2570–3060) g. Two of the seven cases were
monochorionic diamniotic twin pregnancy, and twinto-twin transfusion syndrome was not developed in
either case. One of the twin pregnancies delivered at 37
Volume 23 | Issue 1 | April 2015
35
Demirci O et al.
weeks of gestation while the other one at 34 weeks of
gestation. Development of fetuses was normal in the
twin pregnancy which delivered at 37 weeks of gestation; however, selective intrauterine growth retardation
(IUGR) developed in the other twin pregnancy delivered at 34 weeks of gestation. While critical PS was
observed in the elder fetus, there was perimembranous
ventricular septal defect in the donor fetus.
Chromosome examinations of all cases were normal;
one case had anal atresia. Tricuspid valve Z-score of the
cases with bipartite right ventricle morphology was less
than those with tripartite. Also, in 5 cases with negative
tricuspid valve Z-score, medium tricuspid failure was
detected. Prostaglandin E1 (PGE1) infusion was initiated in all cases as soon as they were born. In 3 bipartite
cases, cyanosis developed at early period despite the
PGE1 infusion, and all had balloon valvuloplasty on
postnatal second day. In one case, BT shunt was performed since cyanosis continued on 5th day after balloon valvuloplasty, no problem observed during 3month follow-up. Another case had operation due to
anal atresia after valvuloplasty; when cyanosis increased
after the operation, the case was referred for BT shunt
but passed away when 15-day-old before shunt was
applied. The other 37-week-old twin with bipartite
morphology was applied BT shunt at the same day since
sufficient clinical response was not received after balloon valvuloplasty. Clinical findings were stable during
3-month clinic follow-up. In four tripartite cases,
cyanosis was kept under control better with PGE1 infu-
sion; balloon valvuloplasty was applied in 3 cases on
postnatal 2nd week (9th, 11th and 12th day, respectively); also ductal stent was placed to one case (case nr. 6).
Fourth case was monitored in the newborn intense care
unit for 54 days by PGE1 treatment on receptor baby
developing selective IUGR; and balloon valvuloplasty
was applied on 55th day (Table 1).
Discussion
Critical PS is a cardiac anomaly which is present at postnatal early period together with right ventricular
hypoplasia and where pulmonary circulation depends on
ductus. It requires postnatal emergency medical and
invasive/surgical treatment. Therefore, diagnosing at
prenatal period and delivering at a tertiary center are
very significant in terms of applying prostoglandin E1
treatment at postnatal period without any delay and to
make preparations for required procedures afterwards.
In our study, we aimed to discuss treatment methods
applied at postnatal period according to the right ventricular morphologies of 7 cases which were diagnosed
as critical PS during prenatal period. In cases where
right ventricular outlet of fetal is congested or closed, it
is the tricuspid valve size which determines the development level of right ventricle.[1] The postnatal treatment
planning of critical PS and PAIVS cases is determined
according to tricuspid valve Z-scores.[6] In compliance
with the literature, we found that tricuspid valve Zscores of those with bipartite right ventricular morphol-
Table 1. Summary of the prenatal and postnatal data of 7 cases with critical pulmonary stenosis.
Case
Week of Chromosomal/
gestation- extra-cardiac
diagnosis
anomaly
Week of gestation
and weight
(percentile)
Cardiac
Right
insufficiency, ventricle/
hydrops
component
Tricuspid
insufficiency–
stenosis/Z-score
Postnatal
treatment
1
25
n/a
39-2950 g (10–50p)
n/a
Two
Exists–medium /-2.02
Balloon valvuloplasty on 2nd day
BT shunt on 5th day - ALIVE
2
24
Anal atresia
37-2650 g (10–50p)
n/a
Two
Exists–medium /-2.05
Balloon valvuloplasty on 2nd day
Exitus on 15th day before BT shunt
3
22 MCDA
twin
n/a
37-2570 g (10–50p)
n/a
Two
Exists – medium/-2.65
Balloon valvuloplasty on 2nd day
BT shunt on 2nd day - ALIVE
4
36
n/a
37-3000 g (10–50p)
n/a
Three
n/a/0.17
Balloon valvuloplasty on 9th day – ALIVE
5
34
n/a
39-3060 g (10–50p)
n/a
Three
n/a/0.14
Balloon valvuloplasty on 11th day – ALIVE
6
32
n/a
38-2450 g (10–50p)
n/a
Three
Exists–mild /-0.49
Balloon valvuloplasty on 12th day+
ductal stent – ALIVE
7
34 MCDA
twin
n/a
34-3150 g (50–95p)
n/a
Three
Exists–mild /-0.65
Balloon valvuloplasty on 55th day – ALIVE
36
Perinatal Journal
Critical pulmonary stenosis with prenatal diagnosis
ogy were less than those with tripartite.[2,7-9] Given the
treatments applied during postnatal period, those with
bipartite were required to have balloon valvuloplasty
despite the prostaglandin treatment and also BT shunt
was required since there was no sufficient recovery.
Similar to our study, Cho et al. reported that BT shunt
requirement was higher in those with bipartite right
ventricular cavity among critical PS and PAIVS cases.[10]
Many studies highlighted that prenatal tricuspid valve
sizes are significant to predict prognosis during postnatal period.[2,7-9] The narrowing of tricuspid valve affects
right ventricular development negatively while tricuspid
valve deficiency affects right ventricular development
positively. Therefore, in cases with high level of narrowing on tricuspid valve, the tricuspid valve deficiency is
significant for the development of right ventricle.[1] In
our study, we found distinctive tricuspid valve deficiency in our 3 bipartite cases which had distinctive narrowing of tricuspid valve (Z-score <-2). It is considered that
the tricuspid valve deficiency increases the volume load
on right ventricle and supports the development of right
ventricle.[1] In cases having only narrowing on the tricuspid valve without any deficiency, it is possible to observe
muscular pulmonary atresia as a result of the overgrowth
of muscle layer on infundibular area.[11] Similarly,
Lowenthal et al. reported that postnatal prognosis was
better in PAIVS and critical PS cases with mid- and
severe deficiency on tricuspid valve.[7]
trimester since hyperthrophy on right ventricle
increases gradually.[15,16]
In monochorionic twin pregnancies, especially in
twin-to-twin transfusion syndrome, the narrowing or
atresia on the right ventricular outlet of the receptor
fetus was higher than the normal population.[12–14] In
our two cases with monochorionic twin pregnancies,
twin-to-twin transfusion syndrome did not develop.
On the other hand, one case had selective IUGR and
critical pulmonary stenosis was found in elder fetus.
Similarly, Gardiner et al. reported in their series of 21
cases that there were 2 cases with monochorionic twin
pregnancy which did not develop twin-to-twin transfusion syndrome.[2] While we diagnosed one of our twin
pregnancy cases at second trimester, we diagnosed
other one at third trimester, and we did not found any
cardiac pathology in second trimester ultrasonography.
In the ultrasonographic screening at 18-22 weeks, right
ventricle can be seen at relatively normal size, and
therefore it can be overlooked. At the same time, the
narrowing on right ventricular outlets displays progression and we are able to detect such patients at third
References
In cases with critical PS, chromosomal anomaly and
extra cardiac anomaly are quite rare. Similarly, we found
in our study no chromosomal anomaly, but anal atresia
as extra cardiac anomaly only in one case. Generally,
cardiac failure and intrauterine growth retardation are
not observed during intrauterine period in cases with
PAIVS and critical pulmonary stenosis.[1] Correlatively,
our cases did not develop any cardiac failure finding.
Except the twin pregnancy with selective intrauterine
growth retardation, we did not find intrauterine growth
retardation in any of our cases.
Conclusion
Consequently, in critical PS cases, the treatment methods to be applied during postnatal period may vary
according to the right ventricle being of two or three
parts and the stenosis level of tricuspid valve.
Therefore, diagnosing at prenatal period and categorizing cases will facilitate to maintain postnatal hemodynamic stability and to plan required invasive and/or
surgical treatment options by initiating prostaglandin
treatment.
Conflicts of Interest: No conflicts declared.
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Embryology, Genetics, Physiology, Echocardiographic
Evaluation, Diagnosis and Perinatal Management of Cardiac
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London: Informa Helatcare; 2008; p: 267–80.
2. Gardiner HM, Belmar C, Tulzer G, Barlow A, Pasquini L,
Carvalho JS, et al. Morphologic and functional predictors of
eventual circulation in the fetus with pulmonary atresia or
critical pulmonary stenosis with intact septum. J Am Coll
Cardiol 2008;51:1299–308.
3. Schneider C, McCrindle BW, Carvalho JS, Hornberger LK,
McCarthy KP, Daubeney PE. Development of Z-scores for
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4. Bolger AF, Eigler NL, Maurer G. Quantifying valvular
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5. Rivera JM, Vandervoort PM, Vazquez de Prada JA, Mele D,
Karson TH, Morehead A, et al. Which physical factors
determine tricuspid regurgitation jet area in the clinical setting? Am J Cardiol 1993;72:1305–9.
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6. Hanley FL, Sade RM, Blackstone EH, Kirklin JW, Freedom
RM, Nanda NC. Outcomes in neonatal pulmonary atresia
with intact ventricular septum. A multiinstitutional study. J
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Congenital pulmonary atresia with intact ventricular septum. Clinicopathologic correlation of two anatomic types.
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7. Lowenthal A, Lemley B, Kipps AK, Brook MM, MoonGrady AJ. Prenatal tricuspid valve size as a predictor of postnatal outcome in patients with severe pulmonary stenosis or
pulmonary atresia with intact ventricular septum. Fetal
Diagn Ther 2014;35:101–7.
12. Zosmer N, Bajoria R, Weiner E, Rigby M, Vaughan J, Fisk
NM. Clinical and echographic features of in utero cardiac
dysfunction in the recipient twin in twin-twin transfusion
syndrome. Br Heart J 1994;72:74–9.
8. Peterson RE, Levi DS, Williams RJ, Lai WW, Sklansky MS,
Drant S. Echocardiographic predictors of outcome in fetuses with pulmonary atresia with intact ventricular septum. J
Am Soc Echocardiogr 2006;19:1393–400.
9. Salvin JW1, McElhinney DB, Colan SD, Gauvreau K, del
Nido PJ, Jenkins KJ, et al. Fetal tricuspid valve size and
growth as predictors of outcome in pulmonary atresia with
intact ventricular septum. Pediatrics 2006;118:e415–20.
10. Cho MJ, Ban KH, Kim MJ, Park JA, Lee HD. Catheterbased treatment in patients with critical pulmonary stenosis
or pulmonary atresia with intact ventricular septum: a single
institute experience with comparison between patients with
and without additional procedure for pulmonary flow.
Congenit Heart Dis 2013;8:440–9.
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13. Lougheed J, Sinclair BG, Fung Kee Fung K, Bigras JL, Ryan
G, Smallhorn JF, et al. Acquired right ventricular outflow
tract obstruction in the recipient twin in twin-twin transfusion syndrome. J Am Coll Cardiol 2001;38:1533–8.
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Breuer J. Long term cardiac follow up of severe twin to twin
transfusion syndrome after intrauterine laser coagulation.
Heart 2006;92:95–100.
15. Todros T, Paladini D, Chiappa E, Russo MG, Gaglioti P,
Pacileo G, et al. Pulmonary stenosis and atresia with intact
ventricular septum during prenatal life. Ultrasound Obstet
Gynecol 2003;21:228–33.
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Evaluation of prenatal invasive procedures:
analysis of retrospective cases
Aybike Tazegül Pekin1, Özlem Seçilmifl Kerimo¤lu1, Setenay Arzu Y›lmaz1,
Nadir Koçak2, Feyza Nur ‹ncesu1, Ayfle Gül Kebapc›lar1, Çetin Çelik1
1
Department of Gynecology & Obstetrics, Faculty of Medicine, Selçuk University, Konya, Turkey
2
Department of Medical Genetics, Faculty of Medicine, Selçuk University, Konya, Turkey
Abstract
Özet: Prenatal invaziv giriflimlerin de¤erlendirilmesi:
Retrospektif olgular›n analizi
Objective: In this study, we aimed to present the results of prenatal invasive procedures carried out in our clinic.
Amaç: Bu çal›flmam›zda amaç, klini¤imizde uygulanan prenatal
invaziv giriflimlerin sonuçlar›n› sunmakt›r.
Methods: The records of the prenatal invasive procedures carried
out between April 2011 and 2014 were analyzed retrospectively, and
the indications, complications and karyotype results of invasive procedures were evaluated.
Yöntem: Nisan 2011–2014 tarihleri aras›nda uygulanan prenatal
invaziv giriflimlerin kay›tlar› retrospektif olarak tarand›, invaziv giriflimlerin endikasyonlar›, komplikasyonlar› ve karyotip sonuçlar›
de¤erlendirildi.
Results: Prenatal invasive procedure was applied to 72 (23.4%)
pregnant women who had only minor and/or major anomalies
according to ultrasonography, 226 (73.3%) patients who referred for
increased risk at screening tests, 5 (1.6%) patients with family history and 5 (1.6%) patients with advanced maternal age. Amniocentesis
was carried out for 81.8% (n=252) of these patients, chorionic villus
sampling for 11.7% (n=36) of them, and cordocentesis due to
advanced week of gestation for 6.5% (n=20) of them. Karyotype
analysis results were normal in 278 (90.2%) patients but no cytogenetic result was obtained in 11 (3.5%) patient, and aneuploidy was
reported in 19 (6.2%) patients (trisomy in 2.9% and other genetic
anomalies / variations in 3.3%). Two patients with karyotype results
as 46XX+22p and 46XY,9qh were followed up. The results of the
patients whose ultrasonography examination did not show any
minor marker or major anomaly were considered as normal variants.
Such pregnancies resulted in healthy live births. Karyotype anomalies also having ultrasonography findings were terminated.
Bulgular: Ultrasonografide tespit edilen sadece minör ve/veya
majör anomalisi olan 72 (%23.4) gebeye, tarama testlerinde artm›fl
risk nedeniyle baflvuran 226 (%73.3) hastaya, aile öyküsü olan 5
(%1.6) hastaya ve ileri anne yafl› nedeniyle 5 (%1.6) hastaya prenatal invaziv giriflim uyguland›. Bu hastalar›n %81.8’ine (n=252) amniyosentez, %11.7’sine (n=36) koryon villus biyopsisi, %6.5’ine
(n=20) ileri gebelik haftas› nedeniyle kordosentez uyguland›. Karyotip analizi sonuçlar› 278 (%90.2) hastada normal, 11 (%3.5) hastada sitogenetik sonuç al›namad› ve 19 (%6.2) hastada anöploidi,
(%2.9 trizomi ve %3.3 di¤er genetik anormallikler/ varyasyonlar)
olarak bildirildi. Karyotip sonucu, 46XX+22p ve 46XY,9qh olan 2
hasta takip edildi. Ultrasonografi de¤erlendirmesinde minör belirteç veya majör anomali saptanmayan hastalar›n sonuçlar› normal
varyant olarak kabul edildi. Bu gebelikler sa¤l›kl› canl› do¤um ile
sonuçland›. Ultrasonografi bulgular› da olan karyotip anomalileri
termine edildi.
Conclusion: Prenatal screening tests are still the major indications
for prenatal invasive procedures. However, minor and/or major
anomalies can be displayed in most of the aneuploidic fetuses; therefore, fetuses established with prenatal diagnosis indication should be
evaluated carefully.
Keywords: Prenatal diagnosis, amniocentesis, chorionic villus sampling.
Sonuç: Prenatal tarama testleri halen prenatal invaziv giriflimlerin
ilk s›radaki endikasyonlar›n› oluflturmaktad›r. Ancak minör ve/veya majör anomaliler anöploidik fetüslerin büyük k›sm›nda görüntülenebilmektedir, bu nedenle prenatal tan› endikasyonu konulan
fetüsler dikkatle de¤erlendirilmelidir.
Anahtar sözcükler: Prenatal tan›, amniyosentez, koryon villus biyopsisi.
Correspondence: Aybike Tazegül Pekin, MD. Selçuk Üniversitesi T›p Fakültesi Kad›n
Hastal›klar› ve Do¤um Anabilim Dal›, Konya, Turkey. e-mail: aybiketzgl@hotmail.com
Received: October 18, 2014; Accepted: February 1, 2015
Please cite this article as: Tazegül Pekin A, Seçilmifl Kerimo¤lu Ö, Y›lmaz SA, Koçak N,
‹ncesu FN, Kebapc›lar AG, Çelik Ç. Evaluation of prenatal invasive
procedures: analysis of retrospective cases. Perinatal Journal 2015;23(1):39–44.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231009
doi:10.2399/prn.15.0231009
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Tazegül Pekin A et al.
Introduction
Methods
In pregnancies with the risk of fetal chromosomal
anomaly, chorionic villus sampling (CVS) at the first
trimester, amniocentesis at the second trimester and
invasive prenatal diagnosis methods such as cordocentesis at further weeks may be carried out for diagnostic
purposes. While all these prenatal invasive methods
can be done mainly for fetal karyotype analysis, they
also can be carried out to identify single gene diseases
such as sickle cell anaemia or thalassemia major, and to
investigate fetal infections, fetal blood type, hematocrit
value, enzymes associated with metabolic diseases and
lung maturation.[1] Fetal blood transfusion, amnioreduction, amnioinfusion, fetal shunt and laser practices
can be can be listed as the other invasive procedures for
fetal treatment purposes.[1] During a few decades, invasive procedure indications have become based on
nuchal translucency and maternal serum biochemistry
parameters rather than being based on advanced
maternal age.[2,3] In this way, with the use of first
trimester screening tests, CVS practices have become
prevalent and they have enabled earlier diagnosis. Also,
using maternal serum markers has increased the detection rates and decreased false positivity rates, thus
decreased invasive procedure rates. With the tests analyzing cell-free fetal DNA (cfDNA) becoming popular
recently, the decrease of false positivity and invasive
procedure rates is expected.[4,5] Karyotype analysis can
be done in case of advanced maternal age, trisomy in
previous pregnancy or history of fetus with sex chromosome anomaly, presence of translocation, inversion
or chromosomal anomaly in spouses, markers indicating aneuploidy or presence of major anomaly in the
ultrasonography, positive prenatal test results,
increased nuchal translucency and maternal anxiety.[6,1]
Amniocentesis is considered to be the easiest method
with the least risk for maternal and fetal morbidity
among prenatal invasive diagnosis methods.[7]
American College of Obstetricians and Gynaecologists
(ACOG) reports the risk of pregnancy loss associated
with the procedure during amniocentesis performed
after 15 weeks of gestation as 1/300–500.[6] Also, it is
reported in experienced centers that the risk of pregnancy loss with CVS is similar with amniocentesis.[6]
Fetal loss risk after cordocentesis is shown as 1.4%.[8] In
our study, we aimed to present the results of prenatal
invasive procedures that we carried out with various
indications in our clinic.
A total of 308 pregnant women were included in the
study who were applied prenatal invasive procedures for
the purpose of karyotype analysis between 2011 and
2014 in our clinic. The approval of Ethics Committee of
the Selçuk University Hospital was obtained for the
study. The consent forms were received from the
patients in our clinic by informing them that their ultrasound images and genetic results can be used in the study
before the examination and the procedure. The cases
were evaluated retrospectively in terms of invasive procedure indications, cell culture success, genetic results
and fetal prognosis. The pregnant women with risk rate
over 1/250 according to the first trimester combined test
result, the pregnant women with risk rate over 1/300
according to second trimester screening tests, pregnant
women having major anomaly or ultrasonographic
markers which may be associated with fetal karyotype
anomaly, pregnant women who are above 40-year-old
but did not have any prenatal screening test and pregnant women with karyotype anomaly risk in their obstetric history were recommended invasive procedures
appropriate for their weeks of gestation. The patients
and their spouses were informed about the indication
related with the procedure, the technique to be applied,
complications and the rates to accomplish result and
their written consents were received. Before the procedure, blood type and HIV and hepatitis B serology of
pregnant women were evaluated. CVS was carried out
transabdominally between 11 and 14 weeks of gestation
under sterile conditions with 18-Gauge (G) needle.
Classical amniocentesis procedure at appropriate week
of gestation was preferred in cases with retroverted
uterus or posterior located placenta which were technically not suitable for transabdominal CVS procedure.
Amniocentesis procedure was carried out between 15
and 20 weeks of gestation with 21-G needle under sterile conditions by entering through a distant zone from
placenta and aspiring 1–2 ml fluid for each week of gestation. First 2 ml amniotic fluid was not examined in
order to avoid maternal contamination. Cordocentesis
procedure was carried out by using 22-G needle in pregnancies older than 21 weeks. By entering through the
placental insertion zone or free floating area of umbilical
cord, 2–3 ml fetal blood was collected from umbilical
vein with an injector washed with heparin. Voluson 730
Expert (General Electric Healthcare, Milwaukee, WI,
USA) and 3.5 MHz convex probe were used during the
procedures. The procedure was carried out after fetus
40
Perinatal Journal
Evaluation of prenatal invasive procedures
and placenta were examined systematically. After the
procedure, a single dose of 300 microgram anti-D
immunoglobulin was administered intramuscularly to
the pregnant women with Rh alloimmunization risk.
Routine antibiotic prophylaxis was not applied. The
patients were discharged in the same day. Fetal loss within three weeks following the procedure was considered
as the complication of the procedure.
The samples collected for genetic analysis were cultured for 1 week for CVS, for 3 days for cordocentesis
and for approximately 15–20 days for amniocentesis
through the methods suitable for the samples, and culture extractions were done. Metaphase preparations
obtained after the culture were stained by using Trypsin
Giemsa banding method (GTG). In all cases, 25
metaphase plates were evaluated for structural irregularities and 50 metaphase plates were evaluated for numerical irregularities. Computerized analysis system was
used in karyotyping analysis. Chromosomal anomalies
were defined according to International System for
Human Cytogenetic Nomenclature (ISCN) 2009.[9]
The statistical analysis of data was done by using
SPSS software, version 16.0 (SPSS, Inc., Chicago, IL,
USA). The data in parametric tests were provided as
mean±standard deviation. Percentage values were used
in groups.
Results
Of 308 pregnant women who undergone invasive procedures, mean age was 31.3±6.4 (range: 16 to 46) years,
gravida was 2.4±1.1 (range: 1 to 7) and parity was 1.2±1.0
(range: 0 to 6). Prenatal invasive test was applied to 72
(23.4%) pregnant women who had only minor and/or
major anomalies according to ultrasonography, 226
(73.3%) patients who referred for increased risk at
screening tests, 5 (1.6%) patients with family history and
5 (1.6%) patients with advanced maternal age. The most
frequent invasive procedure indications were increased
risk at triple test (46%), major and/or minor anomalies
(23.4%), increased risk at first trimester combined test
(17%) and increased risk at quad test (10.3%) (Fig. 1).
Increased nuchal thickness (2.9%) and increased nuchal
translucency (2.3%) where the most frequent ultrasonographic findings among karyotype analysis indications
(Table 1). Amniocentesis was carried out for 81.8%
(252) of these patients, CVS for 11.7% (36) of them, and
cordocentesis due to advanced week of gestation for
6.5% (20) of them. Karyotype analysis results were nor-
Fig. 1. The rates of invasive procedure indications.
mal in 278 (90.2%) patients but no cytogenetic result
was obtained in 11 (3.5%) patient, and aneuploidy was
reported in 19 (6.2%) patients (trisomy in 2.9% and
other genetic anomalies/variations in 3.3%) (Table 2).
Cordocentesis was applied to one (0.3%) of the cases
without cytogenetic result, CVS was applied to two
(0.6%) of them and amniocentesis was applied to eight
(2.5%) of them. There was ultrasonographic marker in
16 (84.2) of 19 fetuses found to have aneuploidy. The
results of two patients, whose karyotype results were
46XX+22p and 46XY,9qh but there was no ultrasonographic finding, were considered as normal variant and
followed up. Such pregnancies resulted in healthy live
births. The follow-ups of two patients whose chromosomal analysis results were found as 46XX/47XX+ mar
(live healthy delivery) and 46XY,inv(9) (intrauterine fetal
death at 33 weeks) were discontinued. Gestational prognoses of these patients were learnt by contacting the
patients. There was major anomaly (omphalocele) in the
fetus whose chromosome structure was reported as
46XY,inv(9). Fifteen pregnancies which were found to
have karyotype anomalies with ultrasonographic findings were terminated upon the requests of patients and
families. Four of the terminated fetuses had minor markers and 11 fetuses had major anomalies. In this way, the
results of three patients were considered as variation and
the aneuploidy rate was calculated as 5.2% (16/308). The
pregnancy of a patient, who undergone cordocentesis
due to the diagnosis of non-immune hydrops fetalis at 20
weeks, was terminated due to the onset of the pains.
Also, another pregnancy undergone CVS due to
increased nuchal translucency at 11 weeks of gestation
Volume 23 | Issue 1 | April 2015
41
Tazegül Pekin A et al.
Table 1. Invasive procedure indications according to ultrasonographic findings.
Ultrasonographic findings
Normal
Bilateral cleft palate/lip
Hypoplastic left heart + hydrops fetalis
AVSD
Hydrops fetalis
Cystic hygroma
Cystic hygroma + omphalocele
Omphalocele
Choroid plexus cyst >10 mm + SUA
Fallot’s tetralogy
Dandy-Walker syndrome
Echogenic intestine grade 3 + ECF
Echogenic intestine grade3 + pyelectasis + increased nuchal thickness
Echogenic intestine grade 3 + pyelectasis + hypoplasic nasal bone
Holoprosencephaly + corpus callosum agenesis
ECF + pyelectasis
Ventriculomegaly/hydrocephaly
Ventriculomegaly + cleft palate-lip + hydrocephaly
VSD+ARSA
Ventriculomegaly + SUA
Absence/hypoplasia of nasal bone
Increased nuchal thickness
Increased nuchal translucency
Corpus callosum agenesis + ventriculomegaly + Fallot’s tetralogy
n=308
%
236
1
1
3
6
5
3
2
2
2
2
2
1
1
2
8
8
1
1
1
3
9
7
1
76.6
0.3
0.3
1
1.9
1.6
1
0.6
0.6
0.6
0.6
0.6
0.3
0.3
0.6
2.6
2.6
0.3
0.3
0.3
1
2.9
2.3
0.3
AVSD: atrioventricular septal defect; ARSA: aberrant right sub-clavian artery; ECF: echogenic cardiac focus; SUA: single umbilical artery; VSD: ventricular septal defect.
was terminated at 13 weeks of gestation. The karyotype
analysis of this fetus was 46,XY,inv(Y)(p11;q11).
Procedure-related fetal loss rate was 0.6%.
Discussion
In our study, we found the most frequent invasive procedure indications as increased risk at triple test (46%)
and major and/or minor anomalies detected by ultrasonography (23.4%) while various amniocentesis series
published in Turkey reported advanced maternal age as
the most frequent invasive procedure indication.[10,11] We
found the invasive procedure rate due to advanced
maternal age as 1.6%, and invasive procedures were recommended due to the advanced maternal age risk only
to the patients who were over 40-year-old and did not
undergo prenatal screening tests. Tongsong et al.
reported advanced maternal age as the most frequent
amniocentesis indication (86.3%), and found invasive
procedure rate associated with anomalies found by ultrasonographically as 0.6%.[12] Tabor et al. also reported
advanced maternal age as the most frequent indication
42
Perinatal Journal
and they reported invasive procedure rate with ultrasonography indication as 9%.[13] While previously the
literature was reporting advanced maternal age as the
50–60% of amniocentesis indications,[13–15] it is not considered as an amniocentesis indication by itself today. In
Table 2. Karyotype analysis results.
Cytogenetic results
N=308
%
Normal
278
90.2
No cytogenetic result
11
3.5
46XY,t(16;22)(p13;q13)
1
0.32
46XY,inv(Y)(p11,q11)
1
0.32
Trisomy 13
1
0.32
46XY+15p
1
0.32
Trisomy 21
6
1.94
Trisomy 18
2
0.64
Triploidy 69 XXX
1
0.32
46XX/47XX+mar
1
0.32
46XX+22p
2
0.64
46XY,inv(9)
1
0.32
46XY,9qh
2
0.64
Evaluation of prenatal invasive procedures
recent years, invasive procedure rates have decreased
recommended due to only advanced maternal age risk[16]
by the prevalent use of prenatal screening tests and
extracellular DNA determination in maternal blood. By
our study, we believe that the reason of the high rates of
invasive procedure rates associated with major and/or
minor anomalies detected by ultrasonography results
from the high number of pregnant women with fetal
anomalies and minor markers referred to our clinic since
our clinic is a reference hospital.
In our study, increased nuchal thickness (2.9%),
increased nuchal translucency (2.3%) were among the
ultrasonographic findings of invasive procedure indications and there were ultrasonographic markers in 16
(84.2%) of 19 fetuses who had aneuploidy. Nyber and
Souter analyzed 7 studies in their meta-analysis where
genetic sonograms were evaluated, and they reported that
nuchal thickness increase was the most frequent marker
followed by choroid plexus cyst, echogenic cardiac focus,
pyelectasis and humerus shortness.[17] On the other hand,
choroid plexus cysts are not considered as a marker for
trisomy 21 today. It has been shown that many ultrasonographic markers do not clearly increase previous trisomy
21 risk of pregnant women; however, it increases 3–4
times in the presence of ventriculomegaly, nuchal thickness increase and aberrant right sub-clavian artery, and
6–7 times in case of hypoplasia of nasal bone.[18]
In our study, we found the rate of detecting chromosomal anomaly in invasive procedures as 5.2%. Due to
the non-existence of concomitant ultrasonographic findings in three patients, presence of similar chromosomal
structure in paternal/maternal chromosomal analysis,
completion of pregnancies with healthy live births and
non-existence of anomaly in postnatal evaluations, cytogenetic changes were considered as variant. Our rate to
detect chromosomal anomaly was higher than the rates
reported in other regions of Turkey[19,20] and the rate of
chromosomal anomalies found as 2.4% in risky group.[21]
We believe that the reason results from the association of
our invasive procedures with the indications and the wide
use of screening tests. First trimester combined test is
applied to all pregnant women in our clinic, and integrated test is carried out on patients if they have mid-level
risk accordingly; however, we recommend second
trimester quad screening test if the patient is considered
not to be at appropriate week. Also, ultrasonography is
performed for all pregnant women in order to evaluate
fetal anomaly between 18 and 23 weeks of gestation.
In 11 (3.5%) of our cases which undergone amniocentesis, there was no reproduction in the culture. We
attributed the reason to the laboratory errors associated
with the period when the genetic laboratory of our hospital was established. In 7 of the patients without reproduction in the culture, analyses were run for 13, 18, 21
and X,Y chromosomes with fluorescence in situ hybridisation (FISH) method. The results evaluated as normal
were confirmed by quantitative fluorescence polymerase
chain reaction (QF-PCR). Four patients recommended
cordocentesis refused the procedure. The literature
reports the rate not obtaining reproduction in the culture after amniocentesis between 15 and 20 weeks as
0.6–1%.[22] However, these rates are reported higher in
the studies performed in Turkey.[19,23]
In our study, we found procedure-related fetal loss
rate as 0.6%. The pregnancy of a patient who undergone cordocentesis with the diagnosis of non-immune
hydrops fetalis was lost at 21 weeks of gestation, and
another pregnancy which undergone CVS due to
increased nuchal translucency at 11 weeks was terminated at 13 weeks of gestation. The karyotype analysis of
this fetus was 46,XY,inv(Y)(p11;q11). Also, we found
that another fetus, which was found to have omphalocele with chromosome structure as 46XY,inv(9), was in
utero ex at 33 weeks of gestation. However, this pregnancy was not deemed as procedure-related loss. In a
study where pregnancy loss rates were compared in
patients who undergone amniocentesis but no invasive
procedure, it was reported that pregnancy loss risk
increased 1% (95% CI, 0.3–1.5%) by amniocentesis.[7]
Although differences were found among studies in a
meta-analysis systematically evaluating complications
associated with amniocentesis and CVS procedures,
pregnancy loss rate before 24 weeks of gestation was
reported as 0.9% after amniocentesis and as 1.3% after
CVS.[24] Second trimester amniocentesis is considered as
a safer method than early amniocentesis and transcervical CVS; however, transabdominal CVS for prenatal
diagnosis purpose before 15 weeks of gestation is recommended as the first option.[25] In our study, we observed
amniotic fluid leakage in 1 patient after amniocentesis at
16 weeks of gestation. The pregnancy of the patient
whose fluid leakage stopped within 48 hours by strict
bed rest resulted with healthy live birth at term.
Amniotic fluid leakage is seen in 1–2% of the patients
after amniocentesis and stops usually by itself; however,
infection, oligohydramnios and fetal loss rate increase in
case of persistent fluid leakage.[26]
Volume 23 | Issue 1 | April 2015
43
Tazegül Pekin A et al.
Conclusion
Amniocentesis is the most easy-to-use invasive prenatal
diagnosis method with the lowest complication rate, and
also the procedure used most frequently in our study for
prenatal diagnostic purposes. However, when first
trimester combined test is preferred most frequently in
screenings, the rate of CVS procedure with similar complication rates will increase and this method will offer
earlier diagnosis opportunity. Also, together with the
nuchal translucency measured according to the standards, wide use of first trimester combined tests which
has lower false positivity rates will decrease unnecessary
invasive procedure rates. Today, the indication of
“advanced maternal age” which comes first in prenatal
invasive procedures has been superseded by the indication of “increased risk at prenatal screening tests.”
Besides, together with the active use of ultrasonography
devices with higher resolution beginning from the early
weeks of gestation, viewable minor and/or major anomalies also become indications for invasive procedures
more frequently. Despite all these practices, the rates of
invasive procedures for fetal karyotyping purposes will
decrease significantly as the tests evaluating extracellular
free fetal DNA in maternal blood are used widely.
Conflicts of Interest: No conflicts declared.
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Original Article
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Investigation of the effects of fetal gender on umbilical
artery and middle cerebral artery Doppler findings
Burcu Artunç Ülkümen, Halil Gürsoy Pala, Y›ld›z Uyar, Yeflim Baytur, Faik Mümtaz Koyuncu
1
Department of Gynecology & Obstetrics, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
Abstract
Özet: Fetal cinsiyetin umbilikal arter ve
orta serebral arter Doppler bulgular›na
etkisinin araflt›r›lmas›
Objective: In this study, we aimed to investigate the effects of fetal
gender on umbilical artery and middle cerebral artery Doppler
measurements.
Amaç: Bu çal›flmada fetal cinsiyetin, umbilikal arter ve orta serebral arter Doppler ölçümlerine etkisini araflt›rmay› amaçlad›k.
Methods: Umbilical artery (UA) and middle cerebral artery (MCA)
Doppler ultrasonographic measurements were screened retrospectively from image and file records of 60 healthy singleton pregnant
women who were on their third trimesters and referred to the
Perinatology Clinic of Celal Bayar University between 2013 and
2014. Umbilical artery and MCA Doppler indexes were calculated
by obtaining at least 3 consecutive waveforms. The pregnancies
were evaluated in two different groups according to fetal gender (31
female fetuses and 29 male fetuses) and compared. The difference
between two groups was analyzed by SPSS v.20.
Results: Female fetuses were identified in 31 (51.67%) out of 60
pregnancies and male fetuses were identified in 29 (48.33%) cases
included in the study. Mean maternal ages of female and male fetuses were 29.14±6.21 and 31.88±5.16 (p=0.162), and mean gestational
weeks were 31.71±3.77 and 33.88±4.41 (p=0.111), respectively.
Umbilical artery PI in female and male fetuses was found as
1.00±0.24 and 1.03±0.21, respectively (p=0.761). Middle artery PI in
female and male fetuses was found as 2.16±0.67 and 1.84±0.85,
respectively (p=0.197). Cerebral-umbilical rate was calculated as
MCA PI/UA PI. Although cerebral-placental rate was not statistically significant, it was higher in female fetuses; while it was 1.86±0.92
in male fetuses, it was 2.23±0.78 in female fetuses (p=0.172).
Conclusion: Today, the new approach is not to ignore the gender of
baby during intrauterine period. The decrease in MCA resistance of
male fetuses should be evaluated in greater studies.
Keywords: Fetal gender, Doppler, middle cerebral artery (MCA),
umbilical artery (UA).
Yöntem: 2013-2014 y›llar›nda Celal Bayar Üniversitesi Perinatoloji Poliklini¤ine baflvuran üçüncü trimesterde olan 60 sa¤l›kl› tekil gebelikte yap›lm›fl olan umbilikal arter (UA) ve orta serebral arter (MCA) Doppler ultrasonografik ölçümleri retrospektif olarak
görüntü ve dosya kay›tlar›ndan tarand›. Umbilikal arter ve MCA
Doppler endeksleri en az ard›fl›k 3 dalga formu elde edilerek hesapland›. Gebelikler fetal cinsiyete göre iki ayr› grupta de¤erlendirildi (k›z fetüsler 31 ve erkek fetüsler 29 olgu) ve karfl›laflt›r›ld›.
Her iki grup aras›ndaki fark SPSS v.20 ile de¤erlendirildi.
Bulgular: Çal›flmaya dahil edilen 60 gebeli¤in 31 tanesinde k›z fetüs (%51.67) ve 29 tanesinde erkek fetüs (%48.33) tespit edildi.
K›z ve erkek fetüslerde s›ras› ile ortalama maternal yafl 29.14±6.21
ve 31.88±5.16 (p=0.162), ortalama gestasyonel hafta 31.71±3.77 ve
33.88±4.41 (p=0.111) olarak tespit edildi. Umbilikal arter PI k›z ve
erkek fetüslerde s›ras› ile 1.00±0.24 ve 1.03±0.21 olarak tespit edildi (p=0.761). Orta serebral arter PI k›z ve erkek fetüslerde s›ras› ile
2.16±0.67 ve 1.84±0.85 olarak tespit edildi (p=0.197). Serebro-umbilikal oran MCA PI/UA PI olarak hesapland›. Serebro-plasental
oran, istatistiksel olarak anlaml› olmamakla birlikte k›z fetuslarda
daha yüksek olarak bulundu; erkek fetüslerde ortalama 1.86±0.92
iken k›z fetüslerde ortalama 2.23±0.78 idi (p=0.172).
Sonuç: Günümüzdeki yeni yaklafl›m intrauterin dönemde bebe¤in
cinsiyetinin göz ard› edilmemesi yönündedir. Erkek fetüslerde
MCA rezistans›nda azalma daha büyük çal›flmalarda de¤erlendirilmelidir.
Anahtar sözcükler: Fetal cinsiyet, Doppler, orta serebral arter
(MCA), umbilikal arter (UA).
Correspondence: Halil Gürsoy Pala, MD. Celal Bayar Üniversitesi T›p Fakültesi Kad›n
Hastal›klar› ve Do¤um Anabilim Dal›, Manisa, Turkey. e-mail: gursoypala@yahoo.com
Received: July 10, 2014; Accepted: February 6, 2015
Please cite this article as: Artunç Ülkümen B, Pala HG, Uyar Y, Baytur Y, Koyuncu FM.
Investigation of the effects of fetal gender on umbilical artery and middle cerebral artery
Doppler findings. Perinatal Journal 2015;23(1):45–49.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231010
doi:10.2399/prn.15.0231010
QR (Quick Response) Code:
Artunç Ülkümen B et al.
Introduction
Ultrasonographic examination is one of the most
important tools of modern obstetric practice. In particular, Doppler ultrasonography provides valuable data
about fetal circulation and fetal hemodynamic condition.[1] The vessels most frequently used for the evaluation of the fetal well-being are umbilical artery (UA),
middle cerebral artery (MCA), and ductus venosus
(DV).[2] In case of placental failure and associated fetal
stress, the increases in umbilical artery resistance
indexes are the leading hemodynamic changes in
fetus.[3] Following these changes, MCA resistance
indexes decrease as a result of cerebral redistribution,
which helps to maintain blood flow towards fetal brain
by this adaptation mechanism.[4]
In the studies of Askling et al. and James, the
increases of placental dysfunction in male fetuses and
of associated gestational complications such as
preeclampsia and ablatio placentae were shown.[5,6]
Also, an increase in preterm labor and postterm pregnancy frequency was found in male fetuses.[7-10]
Intrapartum fetal distress and increased cesarean rates
are also observed more frequently in male fetuses.[11]
Besides, hyperemesis gravidarum and placental invasion anomalies are more frequent in female fetuses.[6]
Based on fetal gender being effective on placentation, we considered that fetal gender might cause a
change in Doppler indexes that we use for placental
perfusion evaluation, and we aimed in this study to
investigate the effect of fetal gender on umbilical artery
and fetal middle cerebral artery flow measurements.
Methods
Sixty healthy singleton pregnant women who were on
their third trimesters between 28 and 36 weeks of gestation and had their Doppler ultrasound examination
in the perinatology clinic of our hospital between
January 2013 and June 2014 were included in the
study. The study group was separated into two groups
by pairing according to week of gestation and maternal
age, and fetuses being male and female. While 29 cases
were identified as male fetuses, 31 cases were female
fetuses. Approval of Local Ethics Committee was
obtained for the study planned retrospectively.
Week of gestation was calculated according to the
last menstrual period (LMP) and it was confirmed by
46
Perinatal Journal
first trimester ultrasound findings. Multiple pregnancies, pregnant women with chronic systemic diseases
(such as diabetes, liver and kidney diseases, connective
tissue disease etc.) and pregnancies with preeclampsia
and intrauterine growth retardation were excluded from
the study. Also, the pregnancies found to have fetal
chromosomal or structural anomalies were excluded
from the study.
Ultrasound measurements were done by using
Voluson 730, RAB 3.5-MHz probe (GE Medical
Systems, Milwaukee, WI, USA). All measurements were
done by a single operator (H.G.P.). Umbilical artery
Doppler measurements were done through free
region.[12,13] MCA Doppler measurement was done on the
axial section where thalamic nuclei are seen on the display. Willis polygon was distinguished by color flow.
The measurements were done through the proximal 1/3
part close to the internal carotid artery with origin.
Doppler indexes were calculated by obtaining 3 consecutive waveforms. Amniotic fluid index (AFI) was considered as the total of amniotic fluid depths measured on 4
quadrants.
The statistical analysis was done by SPSS v.20
(SPSS Inc., Chicago, IL, USA). The results were provided as mean±standard deviation (SD). The p value
less than 0.05 was considered as statistically significant.
The difference between the groups was calculated by
using t-test.
Results
Female fetuses were identified in 31 (51.67%) out of 60
pregnancies and male fetuses were identified in 29
(48.33%) cases included in the study. Mean maternal
ages of female and male fetuses were 29.14±6.21 and
31.88±5.16 (p=0.162), and mean gestational weeks were
31.71±3.77 and 33.88±4.41 (p=0.111), respectively.
Umbilical artery PI in female and male fetuses was found
as 1.00±0.24 and 1.03±0.21, respectively (p=0.761) (Fig.
1). Middle umbilical artery PI in female and male fetuses was found as 2.16±0.67 and 1.84±0.85, respectively
(p=0.197) (Fig. 2). Cerebral-placental rate was calculated as MCA PI/UA PI. Although cerebral-placental rate
was not statistically significant, it was higher in female
fetuses; while it was 1.86±0.92 in male fetuses, it was
2.23±0.78 in female fetuses (p=0.172). The clinical data
about the study group are shown in the Table 1. No sig-
Investigation of the effects of fetal gender on umbilical artery and middle cerebral artery Doppler findings
Fig. 1. UA PI values in female and male fetuses.
Fig. 2. MCA PI values in female and male fetuses.
nificant relation was found between UA PI & MCA PI
and maternal age & parity (Table 2). AFI was found as
14.86±4.28 in male fetuses and 13.99±5.42 in female
fetuses (p=0.594). There was no significant relationship
between AFI and estimated fetal weight (r=0.131; p=
0.368) and the week of gestation (r=0.008; p=0.958).
ing placental perfusion has been analyzed only in one
study so far.[14] A total of 388 term pregnant women were
included in this study carried out by Prior et al., and 212
(54.6%) male and 176 (45.4%) female fetuses were identified in these pregnancies. In this study, no difference
was observed between fetal genders in terms of UA PI.
MCA PI was higher among female fetuses (mean female
fetus value: 1.42; mean male fetus value: 1.34) (p=0.004).
MCA PSV (peak systolic velocity) was higher in female
fetuses (p<0.001). Mean cerebral-umbilical rate was 1.74
in male fetuses and 1.81 in female fetuses (p=0.10).
Umbilical venous velocity was higher in female fetuses
(p=0.009).
Discussion
In our study, although we did not observe any statistically significant level in male fetuses, we identified
decreased MCA resistance and slightly increased umbilical artery resistance. Although different placentation
processes and implantation and angiogenesis pathways
are defined depending on the fetal gender, Doppler difference associated with fetal gender in terms of evaluat-
It was shown in previous studies that male fetuses are
more associated with placental insufficiency and therefore the gestational complications related with placenta-
Table 1. Clinical characteristics of the pregnant women included in the study.
Pregnancies with
male fetuses
n=29
Pregnancies with
female fetuses
n=31
p
Maternal age (mean±SD
31.88±5.16
29.14±6.21
0.162
Parity (mean±SD)
1.06±1.03
0.71±1.10
0.330
Week of gestation (mean±SD)
33.88±4.41
31.71±3.77
0.111
Birth weight (g) (mean±SD)
3160.0±709.67
3021.43±972.09
0.613
UA PI (mean±SD)
1.03±0.21
1.00±0.24
0.761
MCA PI (mean±SD)
1.84±0.85
2.16±0.67
0.197
Cerebral-umbilical rate (mean±SD)
1.86±0.92
2.23±0.78
0.172
AFI (cm) (mean±SD)
14.86±4.28
13.99±5.42
0.594
Volume 23 | Issue 1 | April 2015
47
Artunç Ülkümen B et al.
Table 2. Relationship between UA & MCA PI and maternal age and
parity*.
Maternal age
Parity
UA PI
r
p
0.014
0.922
-0.261
0.089
MCA PI
r
p
0.101
0.489
0.041
0.779
*Spearman’s correlation analysis; r=Spearman’s correlation coefficient
tion failure (such as miscarriage, intrauterine loss,
preeclampsia, IUGR etc.) are observed more frequently
in male fetuses.[5,6] In a study evaluating pregnancies with
loss of end diastolic flow, it was shown that 63.2% of the
cases were male fetuses, and 83% of the pregnancies with
reverse end diastolic flow were male fetuses.[15] Prior et al.
reported that decreased resistance in MCA flow even in
the male fetuses considered to have uterine artery flow
and umbilical artery flow within normal ranges and to
have fetal growth compatible with the week of gestation
and normal placental functions compared to female
fetuses depends on a physiological adaptation to the various levels of placentation in male fetuses.[14] Also,
Ghidini and Salafia, and Clifton showed in their studies
that the progress of angiogenesis is weaker in male fetuses and it is more difficult for male fetuses to adapt poor
maternal environmental conditions.[16,17] By the change of
maternal conditions during intrauterine period, the
responses of male and female fetuses towards these poor
conditions and the steroidogenesis pathways in this
process and protein and gene expressions vary.[17] Male
fetuses may adapt better to the poor intrauterine microenvironment molecularly and metabolically.[17] So, male
fetus differ molecularly even in the implantation and placentation phases of pregnancy. Presence of decreased
resistance in MCA flow even in male fetuses displaying
normal clinical development may show that male fetuses
have a physiological adaptation to the differences in placentation.
Cerebral-umbilical rate is the most reliable measurement showing brain sparing effect in babies with
IUGR.[18] In our study, we did not find any difference
between female and male fetuses in terms of cerebralumbilical rate. However, we also did not expect a significant difference in terms of cerebral redistribution since
our study group consisted of healthy pregnant women at
their third trimesters. In the study of Yücel et al. where
48
Perinatal Journal
Doppler findings of term pregnancies were compared
according to fetus genders, there was no significant difference between female and male fetuses in terms of UA
and MCA pulsatility indexes.[19]
In our study, we did not observe any significant difference in female and male fetuses in terms of AFI. In
their study, Perni et al. reported a positive correlation
between AFI and fetal weight in female fetuses before 38
weeks of gestation.[20] In our study, there was no association between AFI and estimated fetal weight and the
week of gestation.
The weakest aspect of our study was the population
size. Our study was limited with 60 patients since we
planned the study retrospectively and excluded the
babies with chronic disease, placental insufficiency findings or fetal anomaly from the study. By this size, the
power of the study was 0.6 (α-error= 0.05; d=0.5). The
advantage of our study was that it was paired by the
maternal age, parity and the week of gestation when the
cases were separated as female and male fetuses. Also,
measuring values by a single operator minimized the
inter-observer difference.
Conclusion
Consequently, placentation perfusion may vary
depending on the fetal gender. Our preliminary results
we provided here should be confirmed by further comprehensive studies.
Conflicts of Interest: No conflicts declared.
References
1. Alfirevic Z, Stampalija T, Gyte GML. Fetal and umbilical
Doppler ultrasound in high-risk pregnancies. Cochrane
Database Syst Rev 2010;(1):CD007529.
2. Mari G, Abuhamad A, Cosmi E, Segata M, Altaye M,
Akiyama M. Middle cerebral artery peak systolic velocity:
technique and variability. J Ultrasound Med 2005;24:
425–30.
3. Piazze J, Padula F, Cerekja A, Cosmi EV, Anceschi MM.
Prognostic value of umbilical-middle cerebral artery pulsatility index ratio in fetuses with growth restriction. Int J
Gynaecol Obstet 2005;91:233–7.
4. Vyas S, Nicolaides KH, Bower S, Campbell S. Middle cerebral artery flow velocity waveforms in fetal hypoxaemia. Br J
Obstet Gynaecol 1990;97:797–803.
5. Askling J, Erlandsson G, Kaijser M, Akre O, Ekbom A.
Sickness in pregnancy and sex of child. Lancet 1999;354:
2053.
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6. James WH. Sex ratios of offspring and the causes of placental pathology. Hum Reprod 1995;10:1403–6.
7. James WH. Why are boys more likely to be preterm than
girls? Plus other related conundrums in human reproduction. Hum Reprod 2000;15:2108–11.
8. McGregor JA, Leff M, Orleans M, Baron A. Fetal gender
differences in preterm birth: findings in a North American
cohort. Am J Perinatol 1992;9:43–8.
14. Prior T, Wild M, Mullins E, Bennett P, Kumar S. Sex specific differences in fetal mid cerebral artery and umbilical
venous doppler. PLoS One 2013;8(2):e56933.
15. Edwards A, Megens A, Peek M, Wallace EM. Sexual origins
of placental dysfunction. Lancet 2000; 355:203–4.
16. Ghidini A, Salafia CM. Gender differences of placental dysfunction in severe prematurity. BJOG 2005;112:140–4.
9. Cooperstock M, Campbell J. Excess males in preterm birth:
interactions with gestational age, race and multiple birth.
Obstet Gynecol 1996;88:189–93.
17. Clifton VL. Review: Sex and the human placenta: mediating
differential strategies of fetal growth and survival. Placenta
2010;31 Suppl:S33–9.
10. Divon MY, Ferber A, Nisell H, Westgren M. Male gender
predisposes to prolongation of pregnancy. Am J Obstet
Gynecol 2002;187:1081–3.
18. Gramellini D, Folli MC, Raboni S, Vadora E, Merialdi A.
Cerebral-umbilical Doppler ratio as a predictor of adverse
perinatal outcome. Obstet Gynecol 1992;79:416–20.
11. Bekedam DJ, Engelsbel S, Mol BWJ, Buitendijk SE, van der
Pal-de Bruin KM. Male predominance in fetal distress during labor. Am J Obstet Gynecol 2002;187:1605–7.
19. Yücel A, Y›lmazer M, Acar M, De¤irmenci B, Köse S,
Haktan›r A, Fenkçi V, Cevrioglu S. Termde normal gebelerde,
Doppler indeksleri ve non-stres test de¤erlerinin fetus cinsiyetine göre karfl›laflt›r›lmas›. Kocatepe T›p Dergisi 2005;6:
19–24.
12. Burrel SJ, Kingdom JC. The use of umbilical artery Doppler
ultrasonography in modern obstetrics. Curr Opin Obstet
Gynecol 1997;9:370–4.
13. ISUOG Practice Guidelines. Use of Doppler ultrasonography
in obstetrics. Ultrasound Obstet Gynecol 2013;41: 233–9.
20. Perni SC, Predanic M, Cho JE, Kalish RB, Chasen ST.
Association of amniotic fluid ›ndex with estimated fetal
weight. J Ultrasound Med 2004;23:1449–52.
Volume 23 | Issue 1 | April 2015
49
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Original Article
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Perinatal Journal 2015;23(1):50–55
R
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Results of routine first trimester screening tests and
following invasive procedures during pregnancy
Rahime Nida Ergin1, Murat Yayla2
1
Department of Obstetrics & Gyneceology, Faculty of Medicine, Bahçeflehir University, Istanbul, Turkey
2
Obstetrics & Gyneceology Clinic, International Hospital, Istanbul, Turkey
Abstract
Özet: Gebelikte rutin ilk üç ay taramas›n›n
sonuçlar› ve sonras›nda yap›lan tan›sal
giriflimler
Objective: The purpose of this study is to show distribution of
risk in pregnancies which underwent first trimester combined
tests, and investigate general demographic and clinical characteristics of patients, underwent invasive diagnostic tests after screening tests.
Amaç: Bu çal›flmada gebeli¤in ilk üç ay›nda kombine test yap›lan
gebelerde risk da¤›l›m›n›n gösterilmesi, tarama sonras› yap›lan di¤er ifllem ve giriflimler ile tan›sal test uygulanan hastalar›n genel
demografik ve klinik özelliklerinin incelenmesi amaçlanm›flt›r.
Methods: Combined test data of first trimester screening in 20082011 were evaluated retrospectively and cross-sectional. After the
measurement of nuchal translucency (NT), double test was
applied to complete combined test within the same day. Invasive
diagnostic procedures were compared in terms of rate, indications,
karyotype and postnatal outcomes.
Results: A total of 1109 pregnant women were included. Their
mean age was 31.07±3.73 years. Free-βhCG was 1.26±0.94 MoM
and PAPPA was 1.16±0.65 MoM. Mean NT value was 1.60±0.67
mm. With threshold of 1/250, screening test was positive in 3.1%
of the cases. Additional 22 cases due to first trimester screening
and 19 cases due to second trimester screening had invasive procedures (6.4% in total). Invasive procedures revealed karyotype
anomaly in 11.3%. Karyotype anomalies were more frequent in
group (20%) with positive combined test compared to ones performed for other reasons like maternal anxiety.
Yöntem: 2008–2011 y›llar› aras›nda ilk üç ay gebelik taramas›na
ait kombine test verileri retrospektif-kesitsel olarak de¤erlendirildi. Ense kal›nl›¤› (NT) ölçümü sonras›nda ayn› gün içinde kombine testi tamamlamak için ikili test uyguland›. Taramalar›n sonras›nda uygulanan tan›sal giriflimler oran, endikasyonlar›, karyotip ve
postnatal sonuçlar aç›s›ndan karfl›laflt›r›ld›.
Bulgular: Toplam 1109 gebe de¤erlendirmeye al›nd›. Takipteki
gebelerin ortalama yafl› 31.07±3.73 y›ld›. Serbest βhCG ölçümü
1.26±0.94 MoM ve PAPP-A ölçümü 1.16±0.65 MoM saptand›. Birinci üç ayda ortalama NT de¤eri 1.60±0.67 mm bulundu. Eflik
de¤eri 1/250 al›nd›¤›nda olgular›n %3,1’inde tarama testi pozitif
saptand›. ‹lk üç ay taramas› sonunda 22 olguya ve ikinci üç ay taramalar› sonras›nda 19 olguya daha tan›sal giriflim yap›ld›¤› gözlendi (toplamda %6.4). Giriflim yap›lan hastalar›n %11.3’ünde
karyotip anomalisi saptand›. Kombine test sonucu pozitif olan
grupta anne yafl›na ba¤l› anksiyete gibi di¤er nedenlerle giriflim yap›lanlara göre karyotip anomalisi daha fazla (%20) gözlendi.
Conclusion: Although false positive rate is 3.1% in first trimester
combined test, rate of total invasive procedures is more than double (6.4%). Number of invasive diagnostic procedures increased
due to maternal anxiety of age and physicians evaluating only NT
or double tests. With diagnostic procedures, chromosome anomalies reaches 11% and termination need reaches 10%. Invasive
procedures performed due to anxiety of mother or physician
revealed no chromosomal anomaly requiring termination.
Sonuç: Çal›flmam›zdaki gebelik takiplerinde ilk üç ay taramas›nda
kombine testte yanl›fl pozitiflik oran› %3.1 olmas›na ra¤men toplam
giriflim oran› iki kat›ndan fazlad›r (%6.4). Tan›sal ifllem say›s› yafl s›n›r›ndan kaynaklanan anne anksiyetesine ve hekimlerin sadece NT
veya ikili test sonucunu dikkate almalar› nedeni ile artmaktad›r. Tan›sal giriflimlerde %11’lere ulaflan kromozom anomalisi ile %10’lara ulaflan sonland›rma gereksinimi ile karfl›lafl›lm›flt›r. Anne veya hekim anksiyetesine ba¤l› uygulanan giriflimlerin hiçbirinde sonland›rma gerektiren bir kromozom anomalisine rastlanmam›flt›r.
Keywords: Combined test, chorionic villus sampling, amniocentesis, anxiety.
Anahtar sözcükler: Kombine test, koryon villüs biyopsisi, amniyosentez, anksiyete.
Correspondence: Rahime Nida Ergin, MD. Bahçeflehir Üniversitesi T›p Fakültesi Kad›n
Hastal›klar› ve Do¤um Ana Bilim Dal›, ‹stanbul, Turkey. e-mail: drnidaergin@gmail.com
Received: January 12, 2014; Accepted: February 17, 2015
Please cite this article as: Ergin RN, Yayla M. Results of routine first trimester
screening tests and following invasive procedures during pregnancy. Perinatal Journal
2015;23(1):50–55.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231012
doi:10.2399/prn.15.0231012
QR (Quick Response) Code:
Results of routine first trimester screening tests and following invasive procedures during pregnancy
Introduction
By the development of ultrasonographic fetal biometry
measurements and early and effective screening programs based on biochemical methods in the early diagnosis of chromosomal anomalies, maternal preferences
have increased actively.[1-3] Combined test, as one of the
efficient screening programs, includes fetal nuchal
screening and double screening test from maternal
blood consecutively between 11 and 14 weeks of gestation, and chromosome anomaly is used for the risk
determination of trisomy 21 in particular. In this study,
we aimed to show the distribution of combined test
results in pregnant women who underwent combined
screening test between 11 and 14 weeks of gestation
and to investigate general demographic, laboratory and
clinical characteristics of patients who underwent invasive procedures and diagnostic tests according to the
results of screening tests.
Methods
The data of patients for first trimester screenings
between 2008 and 2011 were evaluated retrospectively
and as cross-sectional. Before the screening tests, all
pregnant women were informed and their consents
were obtained for the efficiency of ultrasonography
and biochemical procedure to be carried out. First, the
week and day of gestation were determined. In fetuses
which had 45–84 mm ultrasonographic crown-rump
length (CRL), nuchal translucency (NT) was measured
according to current rules.[1] In addition to this measurement, fetal anatomy was evaluated. Then, in the
same day, 4–6 ml peripheral venous blood was collected for double test (free beta human chorionic
gonadotropin [f-βhCG] and pregnancy-associated
plasma protein A [PAPP-A]) calculation, and it was
studied in the same laboratory with same method in 24
hours.
The risk distribution of f-βhCG and PAPP-A
MoM values reached during screening program and
combined test results were obtained. The patients
whose combined test risk scores were 1/250 and above
were considered as positive and they were informed
about other screening methods and diagnostic methods again. For karyotype analysis, chorionic villus sampling (CVS) at 12–14 weeks of gestation or amniocentesis at 16–20 weeks of gestation was carried out.
Chromosome analyses were performed in the genetic
laboratory of the same institution. In the risk groups
which had and did not have invasive procedures, gestational follow-ups were continued to determine gestational prognosis. The distribution of the numbers and
reasons of CVS and amniocentesis carried out after
screening tests and karyotype results, and perinatal
prognosis of the group which had invasive procedure
were re-investigated after the delivery, and amniocentesis and CVS groups were compared. T-test and
Mann-Whitney U tests were performed for statistical
data, and the value p<0.05 was considered statistically
significant.
Results
In a period of four years, 1109 pregnant women were
included in the study in total. Mean age of the cases
was 31.07±3.73 years. Mean f-βhCG value was
1.26±0.94 MoM and PAPP-A value was 1.16±0.65
MoM in the first trimester. Mean NT value in the first
trimester was 1.60±0.67 mm. When threshold value of
the combined test result was considered as 1/250,
screening test result was positive in 3.15% (35/1109) of
the cases. It was observed that 30 (85.7%) of these 35
cases accepted diagnostic procedure. After first
trimester briefing and screening, additional 22 cases
also requested diagnostic procedures and had invasive
procedures. Given the additional screenings during the
second trimester, additional 19 cases also had diagnostic procedures.
Among pregnant women found to be positive in the
first trimester screening test, 5 (14%) out of 35 cases
did not accept invasive diagnostic method recommended and preferred to decrease their risks by consecutive
screenings, and no chromosomal anomaly finding was
found neither during follow-up nor postnatal period.
Chromosome anomaly was found in 20% (6/30) of
those who underwent CVS or amniocentesis after positive screening finding, and pregnancy was terminated
in all cases. Although combined test result was within
low risk range, both physicians and pregnant women
considering maternal age as too advanced, and separate
interpretation of increased nuchal translucency and
biochemical risk level in consecutive screening tests
caused anxiety and uncertainty in some cases. This anxiety caused pregnant women to prefer CVS or amniocentesis directly or to have second trimester screening
tests. Non-directing consultancy was provided again by
Volume 23 | Issue 1 | April 2015
51
Ergin RN, Yayla M
the physicians who carried out the screening in this
group which had negative screening test results and
requested procedures, and therefore invasive procedures were carried out since they did not change their
minds. No karyotype anomaly was observed in these 22
pregnant women within low risk range. In the last
group consisting of 19 cases, which were examined
during second trimester and found to have positive
results for biochemical test or genetic marker, had 4
structural fetal anomalies and all underwent invasive
procedures. Among them, there were 2 karyotype
anomalies not requiring termination and 2 structural
anomalies which were required to terminate.
In terms of the reasons of the procedures (n=71),
combined test was effective in 30 cases, advanced maternal age in 15 cases, positive genetic sonography in 13
cases, maternal anxiety in 7 cases, and positive result for
second trimester screening test in 6 cases. The reasons
of diagnostic procedures were observed in the first
trimester screening tests in 52/71 cases and in the second trimester screening tests in 19/71 cases. In total,
6.4% of the screened cases (CVS in 1% and amniocentesis in 5.4%) underwent diagnostic procedures.
In 11.27% of the patients which underwent the invasive procedure had karyotype anomaly (three fetuses had
trisomy 21, two fetuses had trisomy 18, two fetuses had
mosaic XXY and one fetus had triploidy). It was determined that karyotype anomalies were more frequent in
the group (6/30: 20%) with positive result for combined,
and less frequent in the group (1/19: 5.3%) with negative result for combined test but positive result for second trimester biochemistry or genetic ultrasonography
screening test and in the group (1/22: 4.5%) with anxi-
Table 1. Results of combined test risk and the distribution of diagnostic procedures.
Risk rate
Number of
screened
pregnant
women
Number pregnant
women underwent
diagnostic
procedure
Number of
karyotype
anomaly
detected
6
>1/250
35
30
1/251-1/1000
70
12
-
1/1001-1/10,000
444
22
1
1/10,001-1/100,000
560
7
1
Total
1109
71
8
ety. In the last two groups, the karyotype anomaly
detected was 47, XXY.
The distribution of screened pregnant women
according to combined test risk results and the distribution of diagnostic procedures performed are shown
in Table 1; karyotype anomalies found are shown in
Table 2, and the comparison of the groups which had
and did not have procedures is shown in Table 3. As
expected, mean maternal age and mean fetal NT were
statistically significant in the group which underwent
procedures. When cases which underwent amniocentesis or CVS were compared, it was seen that mean age
was low but mean fetal NT and risk score were higher
in those underwent CVS (Table 4).
Among the cases which had no karyotype anomaly
after procedure and followed up until delivery delivered, 87.3% of them delivered at term, 9.5% of them
delivered preterm or IUGR but healthy babies, and
3.2% of them had fetal loss at prenatal period. Also, in
3.2% of this group, there was minor anomaly. In none
Table 2. Laboratory and clinical characteristics of karyotype anomalies.
Case
Maternal
age
Week of
gestation
1
40
12
9
2
27
12
2.9
3
40
13
3.2
4
35
12
5
30
12
6
36
7
29
8
31
CVS: Chorionic villus sampling
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Perinatal Journal
NT
(mm)
βhCG
f-β
(MoM)
PAPP-A
(MoM)
Combined
test risk
Diagnostic
procedure
Karyotype
-
-
1/6
CVS
Trisomy 21
1.5
0.5
1/2
CVS
Trisomy 21
2.1
1.0
1/6
Amniocentesis
Trisomy 21
4.5
0.4
0.1
1/2
CVS
Trisomy 18
1.5
0.3
0.4
1/21,836
CVS
Trisomy 18
13
1.7
0.7
0.6
1/3850
Amniocentesis
Mozaic XXY
13
1.2
0.9
0.8
1/50,000
Amniocentesis
Mozaic XXY
13
3.0
0.1
0.06
1/2
CVS
Triploidy
Results of routine first trimester screening tests and following invasive procedures during pregnancy
of the procedures applied due to the anxiety of mother
or physician, no chromosomal anomaly requiring termination was observed. False negative major chromosome anomaly was not observed in any of the cases followed-up, and no such findings were reported to us in
the following 3 years.
Table 3. The mean and standard deviation distribution of age, NT and
biochemical markers in cases.
Procedure
In the studies carried out in Turkey,[5,6] mean fβhCG values were reported between 0.82 and 1.07
MoM and mean PAPP-A values were reported
between 1.06 and 1.61 MoM. In our study group, we
found these values as 1.25 and 1.16 MoM, respectively. f-βhCG value in our study was slightly higher than
the values in other studies. We believe that the difference may result from various laboratory methods. In
the same studies, NT values were found between 1.16
and 1.58 mm. Mean NT value of normal cases we
found in our study was 1.53 mm and it is similar to the
results of other studies.
Including combined test into clinical practice caused
conflicts to determine fetal chromosome anomaly risk in
the use of second trimester tests, increase in false positivity rates and unnecessary invasive procedures.[7]
Applying these tests of two different periods in clinical
practice with various combinations has been improved
by SURUSS (Serum, Urine and Ultrasound Screening
Study) study and it was reported that “Integrated Test”
practice (NT death + PAPP-A in 11 weeks of gestation
and carrying out quad test – αFP, uE3, hCG and inhib-
NT*
βhCG
MoM
PAPP-A
MoM
Yok
Mean
Standard deviation
30.84
3.473
1.53
0.34
1.25
0.93
1.16
0.64
CVS / AS
Mean
Standard deviation
34.43
5.38
2.60
2.14
1.30
1.08
1.04
0.75
Total
Mean
Standard deviation
31.07
3.73
1.60
0.67
1.25
0.94
1.15
0.65
Discussion
Using biochemical parameters as trisomy 21 screening
test efficiently has increased the rates of maternal preferences in gestational follow-up practices.[2] However,
in the perinatology, one of the cornerstones (or even of
the milestones) in screening and determined karyotype
anomalies is to add ultrasonographic nuchal translucency measurement into biochemical analyses as trisomy 21 screening test during relatively early period of
pregnancy such as first trimester.[3] Ultrasonographic
nuchal translucency measurement together with
maternal age and f-βhCG and PAPP-A measurements
from maternal serum between 11 and 14 weeks of gestation are defined as “combined test”. Also, in pregnant
women recommended first trimester combined screening test by adding combined test into the clinical use, it
is seen that the rate of pregnant women accepting procedure increases significantly.[4]
Age*
*: Statistically significant; p<0.05. AS: Amniocentesis, CVS: Chorionic villus sampling
in A – in the early second trimester) was effective.[7,8] In
this prospective study carried out in multiple center
where over 47,000 pregnancies were followed up, it was
stated that it is the best method with 85% early detection rate and 0.9% false positivity rate.[7,8] In our study,
we found false positivity rate as 4.3% for combined
test.[7,8] However, in following modeling and clinical
studies, “Contingent sequential” (recommending invasive diagnostic procedures for those evaluated to have
high risk in first trimester test and carrying out quad test
at second trimester in pregnancies with threshold risk
values) method was shown as the effective method with
the high early detection rate of anomaly and high rate of
false positivity rate which are 1, 3, and 5%.[9,10] Although
it is stated in some publications that contingent sequential screening method has a complex structure and low
detection rate in the comparison of sequential and contingent prenatal Down syndrome screening test,[11] it was
reported in FASTER (First and Second Trimester
Table 4. The mean and standard deviation distribution of age, NT and
biochemical markers in procedures.
Procedure
Age*
NT*
βhCG
MoM
PAPP-A
MoM
CVS
Mean
N
Standard deviation
30.64
11
10.38
4.92
11
2.89
1.16
10
0.79
0.66
10
0.0
AS
Mean
N
Standard deviation
35.11
60
3.64
2.14
56
1.64
1.33
56
1.13
1.11
56
0.77
Total
Mean
N
Standard deviation
34.43
71
5.38
2.60
67
2.14
1.30
66
1.08
1.04
66
0.75
*: Significant difference with Mann-Whitney U test; p<0.05. AS: Amniocentesis,
CVS: Chorionic villus sampling
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Ergin RN, Yayla M
Evaluation of Risk) study that the results of first
trimester combined screening test at 11 weeks of gestation are better than the results of quad test at second
trimester and similar to the results at 13 weeks of gestation.[12] It was shown that both sequential consecutive
screening test and full-integrated screening test have
low false positivity rates and high detection rates for
Down syndrome.[12] However, considering the costs and
time loss to be brought by carrying out these tests routinely and consecutively in general screening procedures, the efficiency and practicality of a well-combined
test should not be overlooked. The results of our study
having 4-year clinical experience show that high anomaly detection rate and low false positivity rates are similar to the rates reported in the literature.[12-14]
Ultrasonographic nasal bone measurement, ductus
venosus, hepatic artery and tricuspid valve flows and
many other parameters have been offered to increase the
detection rates of these tests until recently.[15] In fact, it
was reported that maternal serum sampling before or
simultaneously with NT measurement increased test
performance.[16]
By including combined test into clinical practice in
England, the number of positive Down syndrome
screening test in 2003–2004 decreased in 2008-2009.[17]
This also provided a 72% decrease in the requests to
cytogenetics laboratory and the total screening positivity rate from 9% to 3.1% in 9 years.[17] In our study, false
positivity rate was 3.1% in first trimester screening combined test in the gestational follow-ups, and it is consistent with the results of that study. However, total procedure rate was more than double (6.4%) compared to test
positivity in our study. The reason is the high rate of
invasive procedures due to the anxiety of mother and/or
physician. However, there was no chromosome anomaly
in such cases.
Today, parallel to the technical developments of
molecular biology, detection rates were 98% for trisomy
21, 96% for trisomy 18 and 13, and invasive test rate was
0.7% by including extracellular free fetal DNA in
maternal blood into the combined test.[18,19]
Perhaps, by including molecular tests into routine
practices after their efficiencies are proven by wide
series, anxiety indications of mothers and/or physicians,
which are the major reason for high rate of invasive procedures, may be decreased substantially. It has been
shown that the most significant preference criteria of
mothers among invasive test versus non-invasive follow-
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Perinatal Journal
up methods is to diagnose Down syndrome with at least
95% accuracy with related test.[20] Therefore, investigating extracellular free DNA in maternal blood and combined tests have high potential for patient admission.
Conclusion
Although false positivity rate is 3.1% in first trimester
combined test during pregnancy follow-ups in our
study, the rate of total invasive procedures is more than
double (6.4%). In some pregnant women, the request
for invasive procedure due to anxiety caused by “age
limit”, which is especially an old habit, increases the
number of diagnostic procedures. In addition, physicians taking only nuchal translucency or double test
result into consideration also increase the number of
procedures as well as general anxiety. As a result of the
both first and consecutive second trimester screening
tests, 15.5% of the diagnostic procedures are CVS and
84.5% are amniocentesis. While 73% of these procedures are caused by first trimester screening tests and
briefing, and 27% of them are caused by second
trimester screening tests. At the end of diagnostic procedures, chromosome anomalies reach up to 11% and
termination need reaches up to 10%. No anomaly
requiring termination has been found in any of the
procedures caused by the anxiety of mother or physician.
Proper screening and briefing during pregnancy
may decrease the number of procedures associated
with false positivity, and therefore financial losses and
possible fetal losses. The basic rule to prevent anxiety
is to issue reports which do not include age and double
test results or to interpret such reports accordingly.
Considering the costs and efficiency of trisomy 21
screening tests, “combined test” examination to be carried out by proper individuals and laboratories seems
to continue until other screening tests to be done on
maternal blood become cheaper and are widely used.
Conflicts of Interest: No conflicts declared.
References
1. Nicolaides KH. Screening for chromosomal defects.
Ultrasound Obstet Gynecol 2003;21:313–21.
2. Salonen R, Turpeinen U, Kurki L, Lappalainen M, Ammälä
P, Hiilesmaa V, et al. Maternal serum screening for Down’s
syndrome on population basis. Acta Obstet Gynecol Scand
1997;76:817–21.
Results of routine first trimester screening tests and following invasive procedures during pregnancy
3. Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down’s syndrome.
Prenat Diagn 1997;17:821–9.
4. Tringham GM, Nawaz TS, Holding S, Mcfarlane J, Lindow
SW. Introduction of first trimester combined test increases
uptake of Down’s syndrome screening. Eur J Obstet
Gynecol Reprod Biol 2011;159:95–8.
5. fianl› DB, Kartkaya K. Determination of the median levels of
first trimester screening test parameters in our region.
[Article in Turkish] Perinatal Journal 2012;20:6–11.
6. Özer Ö, Say›n CN, Varol FG. The assessment of nuchal
translucency and serum markers for down syndrome screening with ductus venosus Doppler measurements in the first
trimester. J Turk Ger Gynecol Assoc 2010;11:194–8.
trimester or second-trimester screening, or both, for Down’s
syndrome. N Engl J Med 2005;353:2001–11.
13. Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH.
Screening for trisomy 21 by maternal age, fetal nuchal
translucency thickness, free beta-human chorionic
gonadotropin and pregnancy-associated plasma protein-A.
Ultrasound Obstet Gynecol 2008;31:618–24.
14. Borrell A, Casals E, Fortuny A, Farre MT, Gonce A,
Sanchez A, et al. First-trimester screening for trisomy 21
combining biochemistry and ultrasound at individually optimal gestational ages. An interventional study. Prenat Diagn
2004;24:541–5.
15. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13
weeks. Prenat Diagn 2011;31:7–15.
7. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L,
Mackinson AM. First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine
and Ultrasound Screening Study (SURUSS). J Med Screen
2003;10:56–104.
16. Ekelund C, Wright D, Ball S, Kirkegaard I, Nørgaard P,
Sørensen S, et al. Prospective study evaluating performance
of first-trimester combined screening for trisomy 21 using
repeat sampling of maternal serum markers PAPP-A and
free β-hCG. Ultrasound Obstet Gynecol 2012;40:276–81.
8. Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSS
in perspective. BJOG 2004;111:521–31.
17. Morgan S, Delbarre A, Ward P. Impact of introducing a
national policy for prenatal Down syndrome screening on
the diagnostic invasive procedure rate in England.
Ultrasound Obstet Gynecol 2013;41:526–9.
9. Wright D, Bradbury I, Benn P, Cuckle H, Ritchie K.
Contingent screening for Down syndrome is an efficient
alternative to non-disclosure sequential screening. Prenat
Diagn 2004;24:762–6.
10. Cuckle H, Benn P, Wright D. Down syndrome screening in
the first and/or second trimester: model predicted performance using meta-analysis parameters. Semin Perinatol
2005;29:252–7.
11. Wald NJ, Rudnicka AR, Bestwick JP. Sequential and contingent prenatal screening for Down syndrome. Prenat Diagn
2006;26:769–77.
12. Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock
CH, Bukowski R, et al; First- and Second-Trimester
Evaluation of Risk (FASTER) Research Consortium. First-
18. Nicolaides KH, Syngelaki A, Poon LC, Gil MM, Wright D.
First-trimester contingent screening for trisomies 21, 18 and
13 by biomarkers and maternal blood cell-free DNA testing.
Fetal Diagn Ther 2014;35:185–92.
19. Fairbrother G, Johnson S, Musci TJ, Song K. Clinical experience of noninvasive prenatal testing with cell-free DNA for
fetal trisomies 21, 18, and 13, in a general screening population. Prenat Diagn 2013;33:580–3.
20. Chan YM, Leung TY, Chan OK, Cheng YK, Sahota DS.
Patient’s choice between a non-invasive prenatal test and
invasive prenatal diagnosis based on test accuracy. Fetal
Diagn Ther 2014;35:193–8.
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The association of congenital hand reduction defect
and uterine anomaly
Bülent Kars1, Önder Sakin2, Yasemin Karageyim Karfl›da¤3, Cenk Demir1, Esra Esim Büyükbayrak2
1
Department of Gynecology & Obstetrics, Private Dragos Gülen Medical Center, Istanbul, Turkey
Department of Gynecology & Obstetrics, Dr. Lütfi K›rdar Kartal Training and Research Hospital, Istanbul, Turkey
3
Health High School, K›rklareli University, K›rklareli, Turkey
2
Abstract
Özet: Konjenital el redüksiyon defekti ile uterus
anomalisinin birlikteli¤i
Objective: Fetal hand anomalies can be overlooked in ultrasonographic examinations. In our report, we aim to present the case of
hand reduction defect in a patient with uterine anomaly that we
diagnosed during antenatal follow-up with the use of 2D and 3D
ultrasound examinations.
Amaç: Fetal el anomalileri prenatal ultrasonografik incelemelerde
gözden kaçabilmektedir. Bu yaz›m›zda uterus anomalisi olan bir
olguda; 2 boyutlu ve 3 boyutlu ultrason ile antenatal takipte tan›s›n› koydu¤umuz bir el redüksiyon defekti olgusunu sunmay›
amaçlad›k.
Case: Genetic consultation was provided to a patient who had
absence of hand in one extremity during the ultrasound control performed for triple test while nothing was detected in the ultrasound
for double test screening. After the amniocentesis, the karyotype of
fetus was found as normal (46 --). No other anomaly was observed in
perinatology consultation, anomaly screening and fetal echocardiography. Remaining gestational period of the patient was free of problem and a single 3300 g fetus was delivered by cesarean section
through breech presentation and the pictures of the hand were taken
with the permission of the family.
Olgu: ‹kili test taramas›nda ultrasonda fark edilmeyen ancak üçlü
test amac›yla yap›lan ultrason kontrolünde bir ekstremitesinde el
yoklu¤u tespit edilen hastaya genetik dan›flmanl›k verildi. Hastaya
amniosentez yap›ld›ktan sonra fetüsün karyotipi normal (46 --) olarak geldi. Perinatoloji konsültasyonu, anomali taramas› ve fetal ekokardiyografide efllik eden baflka bir anomali tespit edilmedi. Hastan›n geri kalan gebelik süreci sorunsuz geçti ve 3300 g, tekiz canl›
makat ile prezante olan fetüs sezaryen operasyonu ile do¤urtuldu ve
ailenin izni ile elin foto¤raflar› çekildi.
Conclusion: Congenital hand reduction defects may occur together
with uterine anomalies. Such anomalies can be diagnosed easily during ultrasonographic examinations in early weeks of gestation, and
therefore they should be a part of early anomaly screening procedures.
Sonuç: Konjenital el redüksiyon defektleri uterus anomalileri ile
birliktelik gösterebilen durumlard›r. Bu anomalilerin tan›s› erken
gebelik haftalar›nda yap›lan ultrason incelemesinde rahatl›kla konabilir ve bu nedenle erken anomali taramalar›n›n bir parças› olmal›d›r.
Keywords: Congenital diagnosis, congenital hand deformities.
Anahtar sözcükler: Konjenital tan›, do¤umsal el deformiteleri.
Introduction
Congenital hand reduction defect is the stump end or
full or partial absence of an extremity at the distal of a
point. Transverse forming defect is also known as
transverse reduction defect, transverse melia or transverse arrest.[1]
Congenital anomaly is seen about 1% of newborns,
and 10% of such cases are upper extremity anomalies.
Congenital hand reduction defect is seen one in every
20,000 births. In 50% of these cases, there is simple
transverse reduction defect on forearm or hand, and no
other concomitant anomaly. In other 50% of the cases,
Correspondence: Bülent Kars, MD. Özel Dragos Gülen T›p Merkezi Kad›n Hastal›klar›
ve Do¤um Klini¤i, ‹stanbul, Turkey. e-mail: ‹stanbulent1972kars@yahoo.com
Received: November 27, 2014; Accepted: February 16, 2015
Please cite this article as: Kars B, Sakin Ö, Karageyim Karfl›da¤ Y, Demir C,
Esim Büyükbayrak E. The association of congenital hand reduction defect and
uterine anomaly. Perinatal Journal 2015;23(1):56–59.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231011
doi:10.2399/prn.15.0231011
QR (Quick Response) Code:
The association of congenital hand reduction defect and uterine anomaly
there is more than one reduction and 25% of such
cases also have anomalies in other organs or in craniofacial structures.[2] Congenital hand reduction defect of
upper extremity is usually an isolated anomaly.
Congenital hand anomalies may occur together
with uterine anomalies. In our case, we aimed to discuss hand reduction defect that we diagnosed during
antenatal follow-up with the use of 2D and 3D ultrasound examinations.
Case Report
In the obstetric examination of a 27-year-old patient who
referred to our clinic for the complaint of delayed menstruation, gestation was observed through fetal cardiac
activity which was intrauterine but located on cornual
region close to right uterine. The patient who was pregnant for the first time had no kin marriage and specific
finding in her family history. The patient was prescribed
folic acid support and called for follow-up two weeks
later in terms of cornual pregnancy. In her follow-ups,
the localization of gestational sac was normal. Double
screening test of the patient between 11 and 14 weeks
of gestation were within normal ranges. The patient
who started to take iron support visited the clinic for
AFP screening at 17 weeks of gestation. In the USG
examination, absence of hand in the extremity was
found and genetic consultation was provided to the
patient (Figs. 1 and 2). After the genetic amniocentesis, the karyotype of fetus was found as normal (46 --).
No other anomaly was observed in perinatology con-
sultation, anomaly screening and fetal echocardiography. Remaining gestational period of the patient was
free of problem and a single 3300 g fetus was delivered
by cesarean section through breech presentation and
the pictures of the hand were taken with the permission of the family (Fig. 3). It was found during the operation that uterus was unicornuate, and the presence of
non-communicating horn was detected on the left. Both
tubes and ovaries were normal.
Fig. 2. 3D USG image for the absence of hand.
Fig. 3. Postnatal image for the absence of hand.
Fig. 1. 2D USG image for the absence of hand.
Discussion
The best time to evaluate fetal hands with ultrasound is
between the end of first trimester and mid-period of sec-
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Kars B et al.
ond trimester. During this period, fetus moves frequently and hands are on open position more frequently than
next periods. 3D USG is not necessary; however, it may
be useful to define the morphology better.[3] We detected our case who referred for AFP test at 17 weeks of gestation when we observed the absence of the hand in the
extremity. We applied 3D USG to the patient at the
same session and confirmed the diagnosis.
Hand anomalies may be isolated and also may
accompany to other skeletal and organ anomalies, aneuploidies, syndromes and bone dysplasias.[4,5] Therefore, if
a hand anomaly is detected, the patient should be
referred to a center where all fetal and cardiac anomalies
can be investigated. We therefore carried out genetic
screening by amniocentesis, and investigated other
anomalies at further weeks by perinatology consultation
and anomaly screening. We found no additional concomitant pathology.
Congenital transverse arrest, amniotic band syndrome and Adams-Oliver syndrome (an autosomal
dominant inherited syndrome with aplasia cutis and
asymmetric transverse extremity defects) are among
the distinctive diagnosis of congenital distal hand
reduction defect which is also a complication of early
period chorion villus sampling.
Amniotic band syndrome is usually sporadic and
generally causes asymmetric anomaly.[6] Amniotic
band, which develops after embryologic development
is completed, may cause many hand defects from hand
reduction up to syndactyly.
Congenital transverse arrest is seen rarely although
there are great differences among societies and countries in terms of its incidence rate. Genetics, environmental factors and teratogenic agents are shown as the
reason in the etiology; however, actual reasons have
not been clearly identified. Ninety-eight percent of
congenital transverse arrest is unilateral.[7] It was
reported that transverse arrest may be seen together
with some congenital anomalies; and transverse arrest
was found together with congenital band syndrome in
one case.[1] Unicornuate uterine anomaly was found in
the patient. However, before identifying this uterine
anomaly, it was seen in the ultrasound during the first
referral of the patient that gestational sac was located
in a region close to cornual area. Uterine anomaly was
confirmed by the cesarean section carried out due to
breech presentation in the case. In the literature, it has
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Perinatal Journal
been stated that there is a relationship between uterine
anomalies and extremity defects. It has been reported
that it may cause reduction defects and problems in
extremity development associated with compression in
uterine anomalies.[8]
Extremity processes can be seen with ultrasound at
8 weeks of gestation at the earliest. Femur and
humerus can be seen as of 9 weeks of gestation,
tibia/fibula and radius/ulna as of 10 weeks of gestation,
fingers and toes as of 11 weeks of gestation, and all
long bones can be seen fully as of 11 weeks of gestation.[9,10]
The aim in early anomaly screening is to diagnose
minor or major anomalies before it is too late and to be
able to get early management chance. Therefore, carefully checking the extremities of fetuses in the ultrasound examination to be performed for double test will
help to identify this anomaly at early weeks.
Conclusion
Congenital hand reduction defects may occur together
with uterine anomalies. Such anomalies can be diagnosed easily by carrying out ultrasonographic examinations in early weeks of gestation, and therefore they
should be a part of early anomaly screening procedures.
Conflicts of Interest: No conflicts declared.
References
1. Jain S, Lakhtakia PK. Profile of congenital transverse deficiencies among cases of congenital orthopaedic anomalies. J
Orthop Surg (Hong Kong) 2002;10:45–52.
2. Pilu G, Nicolaides KH. Fetal Anomalilerin Prenatal Tan›s› /
18–23 Gebelik Haftas› Ultrasonu. Çeviri: Hayri Ermifl.
Nashville, TN: Panthenon 2000; p: 94.
3. Reiss RE, Foy PM, Mendiratte V, Kelly M, Gabbe SG. Ease
and accuracy of evaluation of fetal hands during obstetrical
ulrasonography: a prospective study. J Ultrasound Med 1995;
14:813–20.
4. Budorick NE. The fetal musculoskeletal system. In: Callen
PW, ed. Ultrasonography in Obstetrics and Gynecology. 4th
ed. Philadelphia: Saunders; 2000; p: 331–77.
5. Ploeckinger-Ulm B, Ulm MR, Lee A, Kratochwil A,
Bernaschek G. Antenatal depiction of fetal digits with three
dimentional ultrasonography. Am J Obstet Gynecol 1996;
175:571–4.
6. Rypens F, Ziereisen F, Avni F. Perinatal diagnosis of musculoskeletal anomalies. In: Avni FE, ed. Perinatal Imaging:
The association of congenital hand reduction defect and uterine anomaly
From Ultrasound to MR Imaging. New York: Springer;
2002; p: 197-226.
7. Ogino T, Saitou Y. Congenital constriction band syndrome
and transverse deficiency. J Hand Surg Br 1987;12:343–8.
8. Graham JM, Miller ME, Stephan MJ, Smith DW. Limb
reduction anomalies and early in utero limb compression. J
Pediatr 1980;96:1052–6.
9. Van Zalen-Sprock RM, Brons JT, van Vugt JM, van der
Harten HJ, van Geijn HP. Ultrasonographic and radiologic
visualization of the developing embryonic skeleton. Ultrasound
Obstet Gynecol 1997;9:392–7.
10. Timor-Tritsch IE, Farine D, Rosen MG. A close look at
early embryonic development with the high-frequency
transvaginal transducer. Am J Obstet Gynecol 1988;159:
676–81.
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Extrauterine intrapartum treatment procedure in the
unilateral advanced fetal hydrothorax case
Sevil Eraslan, Rauf Meleko¤lu, Ebru Çelik
Department of Gynecology & Obstetrics, Faculty of Medicine, Inönü University, Malatya, Turkey
Abstract
Özet: Tek tarafl› ileri derecede fetal hidrotoraks
olgusunda ekstrauterin intrapartum tedavi
prosedürü
Objective: Congenital hydrothorax is a rare anomaly seen in one
per 10,000–15,000 pregnancies. Progress of the prenatal diagnosis
has enabled the practice of extrauterine intrapartum treatment
(EXIT) procedure in the fetal hydrothorax management. In this
report, we presented a unilateral advanced fetal hydrothorax case
found on ultrasonography at third trimester and underwent EXIT
procedure during delivery.
Amaç: Konjenital hidrotoraks, 10.000–15.000 gebelikte bir görülen nadir bir anomalidir. Prenatal tan›n›n ilerlemesi, fetal hidrotoraks yönetiminde ekstrauterin intrapartum tedavi (EXIT) prosedürünün uygulanmas›na olanak sa¤lam›flt›r. Bu makalede 3. trimesterde ultrasonografide saptanm›fl, do¤umda EXIT iflleminin
uyguland›¤›, tek tarafl› ileri derecede fetal hidrotoraks olgusu sunulmufltur.
Case: No additional anomaly was observed except unilateral pleural
effusion and polyhydramnios on the right in the obstetric ultrasonography of the thirty-five-year-old primigravida patient with no
specific finding in medical and obstetric histories who was referred to
our clinic when pleural effusion and polyhydramnios were found in
fetus at 36 weeks of gestation for the first time during routine obstetric follow-up. EXIT procedure was carried out in the case where
perinatologists, neonatologist and pediatric surgeon were present in
a sterile way during the cesarean operation.
Olgu: Otuz befl yafl›nda primigravid, t›bbi ve obstetrik öyküsünde
herhangi bir özellik saptanmayan, rutin obstetrik takibi s›ras›nda ilk
kez gebeli¤in 36. haftas›nda fetüste plevral efüzyon ve polihidramniyos saptanmas› üzerine klini¤imize yönlendirilen hastada yap›lan
obstetrik ultrasonografide sa¤da tek tarafl› plevral efüzyon ve polihidramniyos d›fl›nda ek anomali izlenmedi. Sezaryen s›ras›nda perinatolog, neonatalog ve çocuk cerrah›n›n steril bir flekilde haz›r olarak bulundu¤u vakada EXIT prosedürü uyguland›.
Conclusion: EXIT procedure is a safe treatment option in fetal
hydrothorax cases since it allows placentofetal circulation during large
amount of pleural effusion discharge from newborn at birth.
Sonuç: EXIT prosedürü, fetal hidrotoraks olgular›nda, do¤umda
yenido¤andan büyük miktarda plevral efüzyonun boflalt›mas› s›ras›nda plasentofetal sirkülasyona izin verdi¤i için güvenli bir tedavi
seçene¤idir.
Keywords: EXIT procedure, hydrothorax, obstetric surgical procedures.
Anahtar sözcükler: EXIT prosedürü, hidrotoraks, obstetrik cerrahi giriflimler.
Introduction
Congenital hydrothorax is the fluid accumulation in
pleural cavity seen in one per 10,000–15,000 pregnancies and it has many reasons such Noonan syndrome,
chromosomal anomalies, immune system disease, car-
diac failure etc.[1,2] Primary congenital pleural effusion
may be unilateral or bilateral; it is usually on the right
side and in cheilosis form.[3] While it may regress spontaneously, it has a variable prognosis reaching up to
fetal or neonatal death.[4,5] Particularly, some of the
bilateral severe congenital hydrothorax cases may
Correspondence: Rauf Meleko¤lu, MD. ‹nönü Üniversitesi T›p Fakültesi Kad›n
Hastal›klar› ve Do¤um Anabilim Dal›, Malatya, Turkey. e-mail: rmelekoglu@gmail.com
Received: November 12, 2014; Accepted: February 24, 2015
Please cite this article as: Eraslan S, Meleko¤lu R, Çelik E. Extrauterine intrapartum
treatment procedure in the unilateral advanced fetal hydrothorax case. Perinatal Journal
2015;23(1):60–64.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231013
doi:10.2399/prn.15.0231013
QR (Quick Response) Code:
Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case
progress rapidly and may result in intrauterine death
due to pulmonary hypoplasia developing as a result of
long-term pressure. Antepartum treatment options
have been developed depending on the increase of
ultrasonography use in prenatal diagnosis. Prenatal
treatment varies depending on the pleural effusion
amount and the diagnosis week of gestation.[6] If isolated pleural effusion is detected before 32 weeks of gestation, it usually has a poor prognosis and it is fatal in
55% of the cases. Mortality rate is 30% in pleural effusion cases diagnosed after 32 weeks of gestation.[7] If
hydrops fetalis accompanies pleural effusion cases,
mortality rate is almost 100%.[6] When prenatal diagnosis is accurate and other fatal anomalies are ruled
out, prenatal invasive procedure is useful, even life-saving in some bilateral cases with poor prognosis. In the
presence of pleural effusion especially diagnosed at
first and second trimesters, thoracic needling is not
curative and thoracoamniotic shunt is preferred in such
cases since recurrence rate is high.[8]
Thoracoamniotic shunt placed by using intrauterine thoracentesis or double pigtail catheter in fetal
hydrothorax management is not always efficient since
it depends on fetal and placental position.
If drainage and ventilation are insufficient for rapid
lung expansion and alveolar gas exchange when thoracentesis is carried out after postnatal emergency intubation in pleural effusion management, permanent
hypoxemic cerebral damage may occur.
In this report, we presented an unilateral advanced
fetal hydrothorax case found on ultrasonography at
third trimester and underwent EXIT procedure.
Case Report
Thirty-five-year-old primigravida patient with no specific finding in medical and obstetric histories was
referred to our clinic when pleural effusion and polyhydramnios were found in fetus at 36 weeks of gestation
for the first time during routine obstetric follow-up. In
the obstetric ultrasonography of the patient whose pregnancy developed spontaneously, it was found that fetal
biometric measurements were consistent with the week
of gestation, there was no additional anomaly except
unilateral pleural effusion and polyhydramnios on the
right (Fig. 1). In the examinations to understand the reasons of fetal pleural effusion of patient whose blood type
was 0 Rh (+), maternal TORCH panel was negative and
fetal echocardiography (ECO) result was normal.
Biochemical examinations, gram staining, culture and
karyotype analyses were done on thoracentesis fluid collected during intrauterine fetal thoracentesis. There was
no reproduction in the culture analysis made on pleural
fluid found to be in chylothorax characteristics according to biochemical parameter. The result of karyotype
analysis was normal. The patient was provided newborn,
pediatric surgery and anesthesia consultations by
Perinatology Department, and cesarean operation
Progress of the prenatal diagnosis has enabled the
practice of extrauterine intrapartum treatment (EXIT)
procedure in the fetal hydrothorax management.[9]
EXIT is the procedure representing the operations
carried out on newborn before cord flow is cut when
fetal-placental unit is functional during the delivery. It
is applied first in congenital diaphragmatic hernia.[10]
While the most frequent indication is external and
internal airway obstructions, there are also other indications. These indications are the removal of obstructive apparatus (gripper, balloon) in the temporary tracheal obstruction, great neck masses (cervical teratoma, lymphangioma), congenital high airway
obstruction syndrome (CHAOS), extracorporeal membrane oxygenization (ECMO).[11]
EXIT procedure helps to gain time for safe adaptation of newborn.[12]
Fig. 1. The image of pleural effusion on the right side of fetus
found at the 36 week of gestation via gray-scale ultrasonography.
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61
Eraslan S, Meleko¤lu R, Çelik E
under elective conditions at 38 weeks of gestation and
EXIT procedure were planned.
Spinal anesthesia was applied in the case where intraoperative perinatologist, neonatologist and pediatric
surgeon were present in a sterile way. No drug was
administered for the relaxation of uterine. By performing hysterectomy through lower segment transverse
incision, 2840 g male baby was delivered. The newborn
was placed on a sterile and flat surface on the legs of
mother as maintaining uteroplacental and placentofetal
circulation, not stretching the cord and on the placenta
level without clamping. While obstetrician was providing maternal hemostasis, the pulse of the umbilical cord
was checked during the procedure. Underwater
drainage was performed by inserting tube thoracostomy
into right pleural cavity via 16G intravenous catheter
through 4th intercostal space (Fig. 2). Newborn evaluated by neonatologist during tube thoracostomy and
drainage did not require intubation. During this period,
about 400 cc pleural fluid in cheilosis form was discharged. The baby, whose cord was clamped on the
fourth minute of labor and who was stabilized after tube
thoracostomy, was transferred to newborn intense care
unit for examination, treatment and follow-up.
In the direct chest radiography during the followups in newborn intense care unit, pneumothorax was
observed in the left lung and therefore thorax tube was
also placed on the left side. No pathological finding was
found in the examinations carried out for pleural effusion etiology. Newborn received respiratory support by
nasal continuous positive airway pressure (nCPAP), and
bilateral thorax tubes were removed when pleural effusion on the right and pneumothorax on the left
regressed on the third day in newborn intense care unit.
On the 14th day in newborn intense care unit, the baby
was discharged in a healthy condition with completely
regressed pleural effusion by recommending newborn
clinical follow-up.
increase depending on the increase of early diagnosis
together with the wide use of antenatal ultrasonography.
Pleural effusion case was first found by Carrol in a pregnant woman at 27 weeks of gestation.[14] Generally, 75%
of the cases are diagnosed at third trimester. In the literature, the earliest diagnosis of pleural effusion case was
reported in the 13 week of gestation.[15] Pleural effusion
is usually detected by ultrasonography at third trimester
and it frequently accompanies to polyhydramnios developing secondarily as a result of the external pressure of
advanced pleural effusion to esophagus.[16]
The prognosis of pleural varies. Perinatal mortality
rate associated with pleural effusion is about 50%.
Considering the clinical progress of such patients, it is
seen that 22% of them regress spontaneously, 43% of
them recover by treatment, and 35% of them result in
fetal or neonatal death. In the absence of polyhydramnios, unilateral pleural effusion cases generally regress
a
b
Discussion
Fetal hydrothorax may occur due to idiopathic and secondary reasons. Among the secondary reasons, there are
cardiac, pulmonary and gastrointestinal malformations,
infectious, hematologic and chromosomal diseases and
immune hydrops.[13]
Fetal hydrothorax is a rare anomaly and its pathogenesis is not known clearly although its incidence rates
62
Perinatal Journal
Fig. 2. EXIT procedure (a). Underwater drainage procedure by inserting thorax tube into the right pleural cavity (b).
Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case
spontaneously. In pleural effusion cases caused by
hydrops, the prognosis is poor independent from the
gestational age and the presence of bilateral effusion.[15]
tion and cooperation both when deciding to apply EXIT
procedure and planning the procedure, and we prepared
plans for interventions against possible complications.
The initial treatment of fetal pleural effusion is the
drainage with aspiration needle in company with ultrasonography. In the meantime, amniocentesis can be performed or the etiology can be investigated by collecting
fetal blood sample. Reasons such as anemia and cardiac
arrhythmia, which are among the causes of pleural effusion but can be treated, should be investigated. In case of
the re-accumulation of pleural fluid in the follow-ups
after drainage, pleuro-amniotic shunt can be considered.[15]
There are two significant complications which may
affect EXIT procedure. First, intraoperative uterine
hemorrhage may require delivering placenta swiftly; and
secondly, since uterine contractions may disorder uteroplacental circulation right after the delivery, halothane
administration may be required to prevent such disorder
and to help the relaxation of uterine. We ensured intraoperative uterine hemostasis rapidly in our case of which
we planned perinatal management and we did not need
any medication reducing uterine contractions.[20]
It was reported in the literature that EXIT procedure was first used when removing tracheal clip placed
to prevent tracheal obstruction caused by severe congenital diaphragmatic hernia.[17]
EXIT is a procedure generally used in the management of extrinsic (teratomas, lymphangiomas) or intrinsic (laryngeal atresia, congenital upper airway obstruction syndrome) obstructive malformations of upper airways diagnosed during prenatal period.[18] The widest
series in the literature was reported by Bouchard et al. in
2002. Thirty-one cases applied EXIT were detailed. In
their series, they did not report any case applied for
pleural effusion, but they stated that they applied EXIT
procedure due to mass in the neck in 13 cases and that
they lost only one case during the EXIT procedure.[19]
First application of EXIT procedure in the severe
advanced fetal bilateral pleural effusion case detected
during prenatal period was reported by Prontera et al. in
the literature.[20]
In the case reported by Prontera et al., which had
pregestational diabetes and normal follow-up results
until 32 weeks of gestation, severe isolated bilateral pleural effusion was found at 38 weeks of gestation, the case
was applied EXIT supported bilateral thoracentesis procedure; the newborn was extubated on the 5th day of its
life, and was discharged on 25th day in a healthy condition. They emphasized that the close and efficient cooperation among anesthetist, obstetrician, neonatologist
and pediatric surgeon to maintain fetoplacental circulation during EXIT procedure, and pointed out the necessity to plan the procedure in detail.[20] In our case, we
worked with the teams of anesthesia, newborn and pediatric surgery in our clinic with continuous communica-
Conclusion
Although intrapartum thoracentesis is a preferred
method in fetuses with severe pleural effusion in the
last period of gestation, thoracentesis together with
ultrasound may cause fetal lung injury and fetal distress
induced by excessive amount of pleural fluid collection,
and this procedure cannot be applied in some cases due
to inappropriate fetal position. EXIT is a procedure
appropriate to use in cases where intrauterine drainage
is technically difficult or impossible and postpartum
drainage may cause deep and extended hypoxia until
pleural fluid drainage is done sufficient enough to
allow lung expansion in the newborn. It is a safe treatment options as it allows placentofetal circulation during the discharge of pleural effusion in large amounts.
More experience and further studies are required in
order to reveal maternal and neonatal effects of applying EXIT procedure in fetal hydrothorax cases, and
this procedure should be limited with viable newborns
appearing only at late gestational periods today.
Conflicts of Interest: No conflicts declared.
References
1. John E. Pleural effusion in the newborn. Med J Aust 1974;1:
102–3.
2. Longaker MT, Laberge JM, Dansereau J, Langer JC,
Crombleholme TM, Callen PW et al. Primary fetal hydrothorax: natural history and management. J Pediatr Surg 1989;24:
573–6.
3. Agrawal R, Aggarwal R, Kriplani A, Bhatla N. Primary Fetal
Hydrothorax. Indian Pediatr 2002;39:92–5.
4. Eddleman KA, Levine AB, Chitkara U, Berkowitz RL.
Reliability of pleural fluid lymphocyte counts in the antena-
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Eraslan S, Meleko¤lu R, Çelik E
tal diagnosis of congenital chylothorax. Obstet Gynecol
1991;78(3 Pt 2):530–2.
13. Lange IR, Manning FA. Antenatal diagnosis of congenital
pleural effusions. Am J Obstet Gynecol 1981;140:839–40.
5. Aubard Y, Derouineau I, Aubard V, Chalifour V, Preux PM.
Primary fetal hydrothorax: a literature review and proposed
antenatal clinical strategy. Fetal Diagn Ther 1998;13:325–
33.
14. Carrol B. Pulmonary hypoplasia and pleural effusions associated with fetal death in utero: ultrasonic findings. AJR Am J
Roentgenol 1977;129:749–50.
6. Pijpers L, Reuss A, Stewart PA, Wladimiroff JW. Noninvasive
management of isolated bilateral fetal hydrothorax. Am J
Obstet Gynecol 1989;161:330–2.
7. Hagay Z, Reece A, Roberts A, Hobbins JC. Isolated fetal
pleural effusion: a prenatal management dilemma. Obstet
Gynecol 1993;81:147–52
8. Gonen R, Degani S, Shapiro I, Samberg I, Sharf M. The
effect of drainage of fetal chylothorax on cardiac and blood
vessel hemodynamics. J Clin Ultrasound 1993;21:265–8.
9. Kern C, Ange M, Morales, Peiry B, Pfister RE. Ex utero intrapartum treatment (EXIT), a resuscitation option for intrathoracic foetal pathologies. Swiss Med Wkly 2007;137:279–
85.
10. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS,
Harrison MR. Operating on placental support: the ex utero
intrapartum treatment procedure. J Pediatr Surg 1997;32:
230–1.
11. MacKenzie TC, Crombleholme TM, Flake AW. The exutero intrapartum treatment. Curr Opin Pediatr 2002;14:
453–8.
12. Henry PY, Aravindan CS, Sivakumar K, Krishna HR.
Extrauterine ›ntrapartum treatment (EXIT) in bilateral primary fetal hydrothorax. Indian J Pediatr 2009;76:99–101.
64
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15. National Institute for Health and Clinical Excellence.
Insertion of pleuro-amniotic shunt to drain fetal pleural effusion (Interventional Procedure Consultation Document)
[Internet]. 2006 [cited 2014 Sept 2]. Available from:
www.nice.org.uk/ip333 overview
16. Mandelbrot L, Dommergues M, Aubry MC, Mussat P,
Dumez Y. Reversal of fetal distress by emergency in utero
decompression of hydrothorax. Am J Obstet Gynecol 1992;
167:1278–83.
17. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS,
Harrison MR. Operating on placental support: the ex utero
intrapartum treatment procedure. J Pediatr Surg 1997;32:
227–31.
18. Hirose S, Farmer DL, Lee H, Nobuhara KK, Harrison MR.
The ex utero intrapartum treatment procedure: looking back
at the EXIT. J Pediatr Surg 2004;39:375–80
19. Bouchard S, Johnson MP, Flake AW, Howell LJ, Myers LB,
Adzick NS, et al. The EXIT procedure: experience and outcome in 31 cases. J Pediatr Surg 2002;37:418–26.
20. Prontera W, Jaeggi ET, Pfizenmaier M, Tassaux D, Pfister
RE. Ex utero intrapartum treatment (EXIT) of severe fetal
hydrothorax. Arch Dis Child Fetal Neonatal Ed 2002;86:
F58–60.
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Case Report
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Perinatal Journal 2015;23(1):65–69
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Goiter in fetus without maternal thyroid disease:
a case report
Önder Sakin1, Bülent Kars2, Yasemin Karageyim Karfl›da¤3, Cenk Demir2, Esra Esim Büyükbayrak1
1
Department of Gynecology & Obstetrics, Dr. Lütfi K›rdar Kartal Training and Research Hospital, Istanbul, Turkey
2
Private Dragos Gülen Medical Center, Istanbul, Turkey
3
Health High School, K›rklareli University, K›rklareli, Turkey
Abstract
Özet: Maternal tiroid hastal›¤› olmayan fetüste
guatr: Olgu sunumu
Objective: The aim is to discuss fetal hypothyroidism which we
consider that its prenatal diagnosis and treatment is significant since
it may cause physical and mental growth retardation in affected
fetuses.
Amaç: Amaç, etkilenen fetüslerde fiziksel ve zihinsel geliflme geriliklerine yol açabildi¤i için prenatal tan› ve tedavisinin önemli oldu¤unu düflündü¤ümüz fetal hipotiroidizmi güncel bilgiler ›fl›¤›nda tart›flmakt›r.
Case: A fetal goiter case was presented which was found during routine ultrasonographic examination at 30 weeks of gestation. The
pregnant women had no thyroid history and all thyroid function
tests were normal including thyroid auto-antibodies in laboratory
tests. In the Doppler ultrasonography, a thyroid gland grown diffusely with increased bloodshot was observed in the fetus. By these
findings, it was considered that fetal goiter would be caused by fetal
hypothyroidism. Amniocentesis or cordocentesis was recommended
as final diagnosis, but the patient refused invasive procedures.
Olgu: Otuz haftal›k gebe iken rutin ultrasonografi incelemesinde
tespit edilmifl bir fetal guatr olgusu sunuldu. Gebenin özgeçmiflinde tiroid hastal›¤› öyküsü mevcut de¤ildi ve laboratuvar testlerinde tiroid otoantikorlar› da dahil tüm tiroid fonksiyon testleri normaldi. Doppler ultrasonografide fetüste diffüz olarak büyümüfl ve
kanlanmas› artm›fl tiroid bezi izlendi. Bu bulgularla fetal guatr›n
fetal hipotiroidizme ba¤l› olabilece¤i düflünüldü. Kesin tan› için
amniyosentez veya kordosentez önerilen hasta invazif giriflimleri
kabul etmedi.
Conclusion: Doppler and ultrasonographic findings are important
for fetal goiter diagnosis and follow-up.
Sonuç: Fetal guatr tan› ve izleminde ultrasonografi ve Doppler
bulgular› önemlidir.
Keywords: Fetal goiter, ultrasonography, prenatal diagnosis.
Anahtar sözcükler: Fetal guatr, ultrasonografi, prenatal tan›.
Introduction
Thyroid disorders are the common endocrine disorders seen during perinatal period. While maternal thyroid anomalies can be diagnosed easily by maternal
serum tests, it is considerably difficult to determine and
diagnose fetal goiter.[1] Different biochemical disorders
in the thyroid hormone synthesis or maternal autoimmune thyroid diseases may cause fetal goiter.[2]
Goiter may be related with fetal hypothyroidism or
hyperthyroidism. Many authors believe the necessity
to determine fetal thyroid function in order to initiate
early treatment process for this condition.[3]
Weiner et al. reported in 1980 for the first time that
they diagnosed fetal goiter by prenatal sonography
method.[4]
Presence of a large thyroid gland on fetal neck region
may cause a difficult delivery due to polyhydramnios by
Correspondence: Önder Sakin, MD. ‹stanbul Dr. Lütfi K›rdar Kartal E¤it. ve Arafl. Hast.,
Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹stanbul, Turkey. e-mail: sakin-onder@hotmail.com
Received: October 29, 2014; Accepted: December 20, 2014
Please cite this article as: Sakin Ö, Kars B, Karageyim Karfl›da¤ Y, Demir C,
Esim Büyükbayrak E. Goiter in fetus without maternal thyroid disease: a case report.
Perinatal Journal 2015;23(1):65–69.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231004
doi:10.2399/prn.15.0231004
QR (Quick Response) Code:
Sakin Ö et al.
esophageal and tracheal pressure and also hyperextension on neck by mass effect.[5]
Fetal hypothyroidism generally depends on antithyroid treatments or endemic iodine deficiency.
Their incidence rate is very low without maternal disease.[6]
iodine or thyroid drug history. In the maternal examination, no examination finding related with thyroid
disease was found. There was also no anomaly in routine gestational analyses.
The 28-year-old patient having her first pregnancy
admitted to our hospital for examination on her 30
weeks of gestation. A great homogeneous mass was
detected on the anterior side of fetal neck during ultrasonographic examination. The mother was married to
her second cousin. There was no thyroid disease in the
history or family history of the mother. She had no
In the ultrasonographic examination, a wide, symmetric and bilobulated mass pressuring trachea on the
anterior side of the fetal neck (47.4x32.2x26.6 mm) (Fig.
1) and mild polyhydramnios were found. Due to its
pressure on esophagus and trachea, angle changes made
by growing thyroid tissue on the background, deterioration in normal traces and concomitant polyhydramnios,
we suspected of the presence of goiter. The mass was in
very vascularized appearance in the Doppler examination (Fig. 2). Fetal heart rate was 220 bpm. It was seen
as a tachycardia in sinusoidal type. No other anomaly
was observed in the fetus. Fetal growth and movements
were normal. Maternal serum thyroid function tests and
thyroid ultrasound results were normal. The mother was
euthyroid, free T3 was 3.34 pg/ml, free T4 was 2.30
ng/dl and TSH was 3.86 IU /ml. Anti-thyroid antibodies were negative. The family was informed about fetal
condition and prognosis. The family refused to have any
invasive procedure such as amniocentesis, cordocentesis
and/or intraamniotic thyroxine treatment. Fetal condition, cardiac activity, fetal development, thyroid dimensions and fetal thyroid bleeding were followed up by
color Doppler. No pathology was seen to explain fetal
tachycardia. In the follow-ups during further weeks,
fetal heart rate was observed within normal ranges.
Since newborn cardiac evaluation was not characterized,
Fig. 1.
Fig. 2.
As in the world, hypothyroidism screening is carried out successfully during newborn period in Turkey
and successful treatments are performed as of the early
period.
However, hypothyroidism developing in fetal period is very significant for the life. The possibility of
congenital hypothyroidism which causes mental retardation but mostly possible to treat is 1 out of each 4000
live birth.[7] Fetal goiter hypothyroidism forming only
10–15% of all congenital hypothyroidism cases is
rarely seen (one out of 4000).[8] Thanks to the development in ultrasonography technology, even though it is
a rare case, the number of reports prepared for fetal
goiter investigations increases day by day.[9]
Case Report
66
2D ultrasound image of fetal goiter.
Perinatal Journal
Doppler ultrasound image of fetal goiter.
Goiter in fetus without maternal thyroid disease
no further evaluation and diagnosis method was
required.
it may cause obstruction due to trachea, and the mechanic problems during delivery may cause morbidity.[12]
The patient delivered a male baby (2600 g) by
cesarean since the delivery began on 36 weeks of gestation and due to pelvic contraction. One-minute
APGAR score was 6, and five-minute score was 7.
There was bilobulated goiter; however, it caused no
obstruction in the airway of newborn and resuscitation
was not required. The baby had no problem with postnatal respiratory adaptation. Postnatal color Doppler
examination confirmed enlarged thyroid gland.
One of the prenatal examinations is Doppler ultrasound. It can be seen in the Doppler ultrasound that neck
vessels spread around soft tissue mass. If it is hypervascular, the increase in the diameters of carotid and jugular
veins can be seen. In case of hyperthyroidism, the diffuse
increased flow in the gland can be seen. In case of
hypothyroidism, peripheral flow around the gland can be
observed.[6]
Iodothyronines in cord blood and TSH measurements confirmed the diagnosis of hypothyroidism. As of
the first neonatal day, oral 50 mcg/day thyroxine hormone treatment was initiated. Fetal tachycardia was not
observed after the delivery. Weight, height and psychomotor developments of child were normal in the first
6 months, and the follow-ups have been maintained.
Discussion
A great goiter may cause fetal neck hyperextension
resulting with malpresentation and complicated delivery
process. The trachea may be obstructed after birth due
to goiter, and this may cause asphyxia and death. During
the delivery, pediatric anesthesia and pediatric ENT
experts should be present in the delivery room with their
intubation and bronchoscopy devices. Neonatal screening programs are successfully used in the diagnosis of
congenital hypothyroidism just after the delivery and
normal development is remedied significantly by early
postnatal treatment. On the other hand, some babies
exposed to congenital hypothyroidism have difficulties
and delays in neuromotor, perception and language abilities despite the postnatal early treatment. Therefore, it
is important to place emphasis on prenatal treatment of
congenital hypothyroidism.[10]
The enlargement of thyroid gland can be seen by
ultrasonography on the anterior side of the fetal neck as
homogenous straight masses with high echogenicity and
distinct edges. The mass can be bilobulated and its size
can enlarge up to 30–35 mm.[11] There are also nomograms for thyroid dimensions appropriate to related
fetal weeks of gestation.
It can be considered that the treatment of fetal
hypothyroidism during intrauterine period is controversial; however, it has been reported that the treatment of
fetuses with large goiter is indicated. The reason is that
However, in another source, it was reported that the
detection of the increase in blood flow towards fetal thyroid is an unreliable finding of hyperthyroid, and even
surprisingly, that increased blood flow was found by using
power Doppler for hypothyroidism.[13] Consequently, it is
not possible to make clear interpretation about thyroid
functions just based on Doppler findings.
Amniotic fluid concentrations of TSH reflect fetal
serum levels properly. However, Bruner and Dellinger
asserted that fetal cord blood measurements are more
reliable, and the evaluation made by amniocentesis is suspicious.[14] Fetal thyroid functions can be evaluated properly by fetal blood sampling method; however, this
method is more risky since it has a 1% risk of fetal
death.[15] However, the publications stating that the
determination of thyroid hormone levels found through
amniotic fluid is not reliable for the diagnosis are predominant.[16]
The association of fetal goiter with chromosomal
anomalies was analyzed, and it was found that it has no
association with aneuploidy. However, in the Pendred
syndrome, hearing loss in sensorineural type and goiter
can be seen. It is an autosomal recessive condition and
thyroid hormone synthesis is insufficient.[6]
Different approaches may be applied in fetal treatment. If fetal goiter is detected in pregnant women
receiving treatment for maternal hyperthyroidism,
decreasing the drug dose by considering the placental
transition of drugs and following up fetal thyroid gland
measurements have been recommended. If fetal goiter
sizes decrease as a result of this treatment, it is recommended to perform no procedure. However, if goiter
continues to enlarge or no respond is received, the
fetus may have hyperthyroid and it is suggested to analyze direct fetal thyroid hormones by doing cordocentesis. If fetal hyperthyroidism is found as a result,
maternal treatment dose is increased until a fetal
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67
Sakin Ö et al.
respond is received. Propylthiouracil is recommended
as the drug.[6]
Intra-amniotic levothyroxine injection as the least
invasive approach in fetal treatment referred by
Abuhamad et al. is a treatment method accepted widely
so far.[17] In this sense, Medeiros-Neto et al. found
increased TSH and decreased sT4 in the cordocentesis
analysis of the fetus with 29×34 mm fetal goiter at 23
weeks of gestation, and they performed intrauterine
levothyroxine treatment. As a result of 400 mcg levothyroxine single-dose injection, the size of thyroid was
found as 4.8×12.5 cm at the end of 4 weeks and the treatment was considered as sufficient.[18]
The treatment dose estimation recommended by
Abuhamad et al. is to do intraamniotic levothyroxine
injection with the dose of 10 mcg/kg according to the
birth weight.[17]
However, as a result of different treatments and
case reports later, Ribault et al. evaluated the treatments of 18 compiled cases. For 1–4 weeks, they made
1–7 injections and found that there was 70–800 mcg
dose difference in each application and 3–23 mc/kg difference in each protocol. Also, fetal hormonal analysis
was performed through amniotic fluid in some cases
while it was done through cord blood in some other
cases. In the conclusion section of that study, the
authors reported that there has been no certain consensus on the treatment of fetal hypothyroidism.[16]
In their recent case report, Khamisi et al. found
maternal hormones within normal ranges and fetal TSH
as >100 mU/l in pregnant women with fetal goiter at 18
weeks of gestation, and they administered intraamniotic
thyroxine for 9 times at intervals of 7–10 days between 24
and 33 weeks of gestation. They administered 10 mcg/kg
in the first 6 applications, and 5 mcg/kg in the last 3 applications. Fetal development was normal; however, the
delivery was made by cesarean at 34 weeks of gestation
due to the suspicion of chorioamnionitis. Since TSH was
higher than 596 mU/L (reference values: 8.0±5.12) in the
cord blood during delivery, thyroxine treatment was initiated just after the delivery. In the conclusion section of
the investigation, it was indicated that new investigations
are required for intraamniotic thyroxine treatment.[2]
Conclusion
As a conclusion, ultrasound and Doppler examinations,
diagnosing and following up fetal goiter are of vital
68
Perinatal Journal
importance. Fetal hypothyroidism is a negative pathology for the development of central nervous system and
physical and mental development. Fetal goiter which is
not present in the ultrasound during the early periods
but becomes evident in the advanced weeks of gestation
should not be overlooked. Mental retardation and other
development disorders can be prevented by early diagnosis and treatment. Therefore, we believe that it will be
useful to remember fetal goiter in the ultrasonographic
screenings even during advanced weeks of gestation.
Conflicts of Interest: No conflicts declared.
References
1. Singh PK, Parwin CA, Gronowski AM. Establishment of
reference intervals for markers of fetal thyroid status in
amniotic fluid. J Clin Endocrinol Metab 2003;88:4175–9.
2. Khamisi S, Lindgren P, Karlssson FA. A rare case of
dyshormonogenetic fetal goiter responding to intra-amniotic thyroxine injections. Eur Thyroid J 2014;3:51–6.
3. Perrotin F, Sembely-Taveau C, Haddad G, Lyonnais C,
Lansac J, Body G. Prenatal diagnosis and early in utero management of fetal dyshormonogenetic goiter. Eur J Obstet
Gynecol Reprod Biol 2001;94:309–14.
4. Weiner S, Scharf JI, Bolognese RJ, Librizzi RJ. Antenatal
diagnosis and treatment of a fetal goiter. J Reprod Med 1980;
24:39–42.
5. Davidson KM, Richards DS, Schatz DA, Fisher DA.
Successful in utero treatment of fetal goiter and hypothyroidism. N Engl J Med 1991;324:543–6.
6. Paula JW, Anne K, Roya S, Janice LB, Karen YO, Michael
DP. Face and neck anomalies – Goiter. Diagnostic imaging
obstetrics. 2nd edition. Utah Amirsys 2013. p: 4/54–5.
7. Delange F. Neonatal screening for congenital hypothyroidism: results and perspectives. Horm Res 1997;48:51–61.
8. Fisher DA. Fetal thyroid function: diagnosis and management of fetal thyroid disorders. Clin Obstet Gynecol 1997;
40:16–31.
9. Meideros-Neto GA, Stanbury JB. Inherited Disorders of the
Thyroid System. Boca Raton: CRC Pres; 1994; p: 1–218.
10. Morine M, Takeda T, Minekawa R, Sugiyama T, Wasada K,
Mizutani T, et al. Antenatal diagnosis and treatment of a case
of fetal goitrous hypothyroidism associated with high-output
cardiac failure. Ultrasound Obstet Gynecol 2002;19:506–9.
11. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse
DJ, Spong CY. Tiroid ve di¤er endokrin bozukluklar.
Williams Obstetrik. 23. bask›. Istanbul: Nobel T›p Kitapevi;
2010. p. 1128–35.
12. Mestman JR. Tyroid and parathyroid diseases in pregnancy.
In: Gabbe SG, Niebly JR, Simpson JL, editors. Obstetrics:
normal and problem pregnancies. 5th edition. London:
Churchill Livingstone; 2007. p.1023–9.
13. Merz E. Obstetrik ve jinekolojide ultrason. Çeviri: Özden S.
2. bask›. Cilt 1. ‹stanbul: Do¤an T›p Kitapevi; 2002. p.
247–52.
Goiter in fetus without maternal thyroid disease
14. Bruner JP, Dellinger EH. Antenatal diagnosis and treatment
of fetal hypothyroidism. A report of two cases. Fetal Diagn
Ther 1997;12:200–4.
15. Simsek M, Mendilcioglu I, Mihci E, Karagüzel G, Taskin O.
Prenatal diagnosis and early treatment of fetal goitrous
hypothyroidism and treatment results with two-year followup. J Matern Fetal Neonatal Med 2007;20:263–5.
16. Ribault V, Castanet M, Bertrand AM, Guibourdenche J,
Vuillard E, Luton D, et al.; French Fetal Goiter Study
Group. Experience with intraamniotic thyroxine treatment
in nonimmune fetal goitrous hypothyroidism in 12 cases. J
Clin Endocrinol Metab 2009;94:3731–9.
17. Abuhamad AZ, Fisher DA, Warsof SL, Slotnick RN, Pyle
PG, Wu SY, et al. Antenatal diagnosis and treatment of fetal
goitrous hypothyroidism: case report and review of the literature. Ultrasound Obstet Gynecol 1995;6:368–71.
18. Medeiros-Neto G, Bunduki V, Tomimori E, Gomes S,
Knobel M, Martin RT, et al. Prenatal diagnosis and treatment
of dyshormonogenetic fetal goiter due to defective thyroglobulin synthesis. J Clin Endocrinol Metab 1997;82:4239–42.
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Letter to the Editor regarding
“Extrauterine intrapartum treatment procedure in
the unilateral advanced fetal hydrothorax case”
Baflak Kaya, Ali Gedikbafl›
Perinatology Unit, Gynecology & Obstetrics Clinic, Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey
This letter has been written for the aspects to criticize for the EXIT procedure in the case report of unilateral advanced fetal hydrothorax case published in Perinatal Journal.[1] Although various treatment and management recommendations and studies have been provided
for fetal hydrothorax in the literature, better results are
obtained by using improved fetal treatment methods.
If hydrothorax develops before 27 weeks of gestation, pulmonary development is affected and cardiac failure and intrauterine loss may occur associated with cardiac and central vein pressure.[2] Besides, isolated fetal
hydrothorax developing at late second trimester and
third trimester may not cause hypoplasia.[3] Poor prognostic factors are bilateral effusion development, nonregression of effusion spontaneously, hydrops and prematurity.[4]
The type of treatment during prenatal period is determined primarily according yo the severity of effusion
and diagnosis week of gestation. Conservative management may be preferred since spontaneous regression
may develop in the presence of mild-mid unilateral
pleural effusion not causing mediastinal shift and
hydrops and not accompanied by polyhydramnios.[5,6] If
rapid increase in effusion, hydrops or polyhydramnios
development is observed during the follow-up, invasive
fetal treatment should be performed by using thoracoamniotic shunt. When thoracoamniotic shunt procedure is significant especially before 36 weeks of gestation,
thoracentesis or thoracoamniotic shunt can be preferred
in further weeks of gestation. Thoracoamniotic shunt
should be preferred primarily in the presence of severe
pleural effusion where mediastinal shift is accompanied
by hydrops or polyhydramnios.[5,7,8] Direct shunt application should also be considered in hydropic fetuses with
bilateral effusion.[9] Nicolaides and Azar reached 50%
survival rate in hydrothorax cases with non-immune
hydrops by applying thoracoamniotic shunt.[10]
Decompression of effusion fluid by thoracentesis allows normal pulmonary development to continue, also
may fix hydrops and polyhydramnios.[11] It also helps to
diagnose for the etiology of hyrops and pleural effusion.[6,12] However, since fluid is accumulated rapidly in
24–48 hours in the most of the cases, thoracoamniotic
shunt should be preferred especially in the cases detected
in the early second trimester.[8,13] On the other hand, while some authors prefer thoracentesis in the initial treatment, they apply thoracoamniotic shunt in case of reaccumulation of pleural effusion.[13] It may not be always
possible to apply thoracoamniotic shunt due to the inappropriate fetal position and increased fetal skin edema.
Transplacental application during the procedure is not
preferred for thoracoamniotic shunt.[6] In such cases
where thoracoamniotic shunt cannot be applied, multiple thoracentesis, conservative follow-up of hydropic fetus
or early labor of fetus are other possible treatment options.[13]
Since prematurity is a poor prognostic factor affecting survival, it is recommended to carry out the delivery
Correspondence: Ali Gedikbafl›, MD. Kanuni Sultan Süleyman E¤itim ve Araflt›rma Hast.,
Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹stanbul, Turkey. e-mail: ali.gedikbasi@kssh.gov.tr
Received: February 24, 2015; Accepted: February 24, 2015
Please cite this article as: Kaya B, Gedikbafl› A. Letter to the Editor regarding
“Extrauterine intrapartum treatment procedure in the unilateral advanced fetal
hydrothorax case”. Perinatal Journal 2015;23(1):70–71.
©2015 Perinatal Medicine Foundation
Available online at:
www.perinataljournal.com/20150231014
doi:10.2399/prn.15.0231014
QR (Quick Response) Code:
Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case
in tertiary centers at 37-38 weeks of gestation.[5] It is reported that draining mid-severe pleural effusion just before the delivery helps neonatal resuscitation and ventilation support.[5,6] However, Klam et al. found no difference between those applied thoracentesis just before
the delivery and postpartum practices in terms of Apgar
score, entubation and ventilation requirements and survival rates.[8]
References
In the case presented, it is seen that thoracentesis was
applied to investigate the etiology of pleural effusion at
36 weeks of gestation and to treat the case. In this case,
in the presence of appropriate fetal position, thoracoamniotic shunt treatment could be planned if transplacental transition was not required technically.
3. Gül A, Aslan H, Cebeci A, Polat ‹, Agral› G, Ceylan Y.
Primary fetal hydrothorax: successful perinatal outcomes
with single thoracentesis just prior to delivery. J Turk Ger
Gynecol Assoc 2004;5:143–6.
Extrauterine intrapartum treatment (EXIT) can be
useful in cases which are near term or at term with severe pleural effusion where intrauterine drainage failed.
Prontera et al. who defined EXIT procedure for the first
time due to fetal hydrothorax carried out this procedure
in a case which had bilateral severe pleural effusion, increased central venous pressure findings, cardiac diastolic function disorder and with lungs completely collapsed and echogenic. Fetal thoracentesis could not be applied due to polyhydramnios and fetal position, and postnatal drainage was not preferred due to the presence of
bilateral and severe pleural effusion and the concern of
postnatal long and severe hypoxia. Therefore, thoracentesis and EXIT procedure were preferred as the least
complicated methods.[2]
When patients who were applied EXIT procedure
and other cases delivered by cesarean section were compared in terms of maternal complications, wound site
complications and estimated blood loss were more in cases who were applied EXIT procedure.[14]
As congenital fetal hydrothorax is a rare clinical condition with limited number of case reports in the literature, there are disputes about the treatment options and
most suitable delivery time. First of all, it is required to
refer such cases to tertiary centers and to plan treatment
and delivery in such centers. The treatment should be
planned according to the characteristics and clinical
condition of current case, the experience of the team
which will carry out invasive procedure, and the suitability of technical conditions.
Conflicts of Interest: No conflicts declared.
1. Eraslan S, Meleko¤lu R, Çelik E. Tek tarafl› ileri derecede
fetal hidrotoraks olgusunda ekstrauterin intrapartum tedavi
prosedürü. Perinatoloji Dergisi 2015;23:60–4.
2. Prontera W, Jaeggi ET, Pfizenmaier M, Tassaux D, Pfister
RE. Ex utero intrapartum treatment (EXIT) of severe fetal
hydrothorax. Arch Dis Child Fetal Neonatal Ed 2002;86:
F58–60.
4. Aubard Y, Derouineau I, Aubard V, Chalifour V, Preux PM.
Primary fetal hydrothorax: a literature review and proposed
antenatal clinical strategy. Fetal Diagn Ther 1998;13:
325–33.
5. Yinon Y, Kelly E, Ryan G. Fetal pleural effusions. Best Pract
Res Clin Obstet Gynaecol 2008;22:77–96.
6. Petersen S, Kaur R, Thomas JT, Cincotta R, Gardener G.
The outcome of isolated primary fetal hydrothorax: a 10year review from a tertiary center. Fetal Diagn Ther
2013;34:69–76.
7. Pellegrinelli JM, Kohler A, Kohler M, Weingertner AS,
Favre R. Prenatal management and thoracoamniotic shunting in primary fetal pleural effusions: a single centre experience. Prenat Diagn 2012;32:467–71.
8. Klam S, Bigras JL, Hudon L. Predicting outcome in primary
fetal hydrothorax. Fetal Diagn Ther 2005;20:366–70.
9. Derderian SC, Trivedi S, Farrrell J, Keller RL, Rand L,
Goldstein R, et al. Outcomes of fetal intervention for primary hydrothorax. J Pediatr Surg 2014;49:900–3.
10. Nicolaides KH, Azar GB. Thoraco-amniotic shunting. Fetal
Diagn Ther 1990;5:153–64.
11. Cardwell MS. Aspiration of fetal pleural effusions or ascites
may improve neonatal resuscitation. South Med J 1996;89:
177–8.
12. Smith RP, Illanes S, Denbow ML, Soothill PW. Outcome of
fetal pleural effusions treated by thoracoamniotic shunting.
Ultrasound Obstet Gynecol 2005;26:63–6.
13. Deurloo KL, Devlieger R, Lopriore E, Klumper FJ, Oepkes
D. Isolated fetal hydrothorax with hydrops: a systematic
review of prenatal treatment options. Prenat Diagn 2007;27:
893–9.
14. Noah MM, Norton ME, Sandberg P, Esakoff T, Farrell J,
Albanese CT. Short-term maternal outcomes that are associated with the EXIT procedure, as compared with cesarean
delivery. Am J Obstet Gynecol 2002;186:773–7.
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PERINATAL
JOURNAL
Volume 23 | Issue 1 | April 2015
C o n te n ts
Original Article
Case Reports
Letter to Editor
Ultrasonographic evaluation of ventriculomegaly cases
Hakan Kalayc›, Halis Özdemir, Ça¤r› Gülümser, Ayfle Parlakgümüfl, Tayfun Çok,
Ebru Tar›m, Filiz Bilgin Yan›k
1
Perinatal outcomes of patients diagnosed borderline gestational diabetes mellitus
Gök Özgül, Rauf Meleko¤lu, Sevda Yeleç, ‹pek Eskiyörük, Fatma Tuncay Özgünen
6
Health practices of pregnant women in Gumushane City Center
Handan Özcan, Nezihe K›z›lkaya Beji
13
The evaluation of pregnancies complicated by eclampsia:
retrospective analysis of 37 cases in our clinic
Aytekin Tokmak, Korkut Da¤lar, Ali ‹rfan Güzel, Bergen Laleli, Salim Erkaya, Dilek Uygur
20
Factors affecting postpartum depression in Diyarbak›r
Ali Emre Tahao¤lu, Cihan To¤rul, Mehmet ‹rfan Külahç›o¤lu, Beflire Ayd›n Öztürk,
Deniz Balsak, Hanifi Bademk›ran, Erdo¤an Gül, Ümit Görkem, Tayfun Güngör
26
Analysis of maternal serum and urinary lipocalin-2 levels
Yeflim Bayo¤lu Tekin, Ülkü Mete Ural, Aynur K›rbafl, fienol fientürk, Figen K›r fiahin
30
Critical pulmonary stenosis with prenatal diagnosis: a case series and review of literature
Oya Demirci, Taner Yavuz, Resul Ar›soy, Emre Erdo¤du, P›nar Kumru, Oya Pekin
34
Evaluation of prenatal invasive procedures: analysis of retrospective cases
Aybike Tazegül Pekin, Özlem Seçilmifl Kerimo¤lu, Setenay Arzu Y›lmaz, Nadir Koçak,
Feyza Nur ‹ncesu, Ayfle Gül Kebapc›lar, Çetin Çelik
39
Investigation of the effects of fetal gender on umbilical artery and
middle cerebral artery Doppler findings
Burcu Artunç Ülkümen, Halil Gürsoy Pala, Y›ld›z Uyar, Yeflim Baytur, Faik Mümtaz Koyuncu
45
Results of routine first trimester screening tests and following invasive procedures
during pregnancy
Rahime Nida Ergin, Murat Yayla
50
The association of congenital hand reduction defect and uterine anomaly
Bülent Kars, Önder Sakin, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak
56
Extrauterine intrapartum treatment procedure in the unilateral advanced
fetal hydrothorax case
Sevil Eraslan, Rauf Meleko¤lu, Ebru Çelik
60
Goiter in fetus without maternal thyroid disease: a case report
Önder Sakin, Bülent Kars, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak
65
Letter to the Editor regarding “Extrauterine intrapartum treatment procedure in the
unilateral advanced fetal hydrothorax case”
Baflak Kaya, Ali Gedikbafl›
70