RIGA STRADIŅŠ UNIVERSITY
VITA ZIDERE
PRENATAL
ECHOCARDIOGRAPHIC
DIAGNOSTICS AND
RESULTS IN LATVIA
In partial fulfillment of the
PhD degree requirement
RIGA - 2004
The research was done at Riga Stradini University Children Cardiology clinic,
the Latvian State Children Cardiology Centre
in the period from January I, 1998 till April 30,2003
Supervisor of research:
Habil. Doctor of Medicine, Professor Aris Lacis
Riga Stradini University Children Cardiology clinic, the Latvian State
Children's Cardiology Centre
Research consultant: Doctor of Medicine, Professor Lindsey D Allan, Harris
Birthright Centre for Fetal Medicine Research, King's College Hospital,
London, UK
Official reviewers:
Dr. habil. med., Prof. Laila Feldmane, RigaStradinS University
Dr. med.,asoc. Prof. Uldis KalninS, University of Latvia
Dr. habil. med., Prof. Alicija Dranenkiene, University of Vilnius, Lithuania
The defense of the thesis will take place at the Riga Strading University on
the 6 of May 2004 at 3 p.m.
Address: 16 Dzirciema Street, Riga, Latvia, LV-1007
INTRODUCTION
The heart and great arteries anomalies are among the most common pathologies
in children. About half of them are lethal or call for a surgical intervention.
Congenital heart disease (CHD) according to the data of the leading specialists
in the world are seen in 8-11 per 1000 live borns [Allan L.D., 2000; Buskens
E. et al., 1996; McGahan J.R, 1991; Stumpfen I. et at., 1996] and in about 30
per 1000 still borns each year [Jeanty P., Pilu G.,1999].
The etiology of heart diseases is not uniform and they are likely to develop as
a result of interaction of several factors, such as genetic and environmental
factors (for example, the influence of teratogenous factors, virus infections,
etc.) [Burn J. etal., 1998; Jeanty P. 1996].
Echocardiography is successfully used in the assessment of fetal heart structures
and functions; it is the only prenatal imaging diagnostic method [Eronen M.,
1997; Gembruch U., 1997].
Association for European Paediatric Cardiology (AEPC) has defined a fetal
cardiology as a subspecialty for children cardiology and has worked out the
guidelines to facilitate the development of fetal cardiology [2003]. The
beginning of prenatal cardiology development is dated from the end of
1970-ties and the beginning of 1980-ties, when ultrasonography was introduced
into the daily obstetrics routine. Consecutively the children cardiologists were
examining the neonatal hearts by using the first echocardiographs. Due to close
professional cooperation it was possible to develop the methods of fetal heart
examination. In the medical centers of Europe and developed countries, the
fetal heart examination took an active start by introducing specialized
educational syllabuses for gynaecologists whose responsibility was to follow
up the pregnant woman and to do the ultrasonography of the fetus [Allan L.D.
et al., 1989; Sharland G.K. et al., 1992; The Fetal working Group of AEPC,
2003]. Simultaneously the diagnosing of fetal heart pathologies was undertaken,
as well as developing cardiology centres in several countries in the world.
Among the pioneers in this field are Wladimiroff group in Rotterdam, the
Netherlands, Bobbins group in Yale ,the USA, Lindsay Allan who established
a prenatal cardiology clinic in England, in Guy's hospital in London, David
Sahn in Portland, the USA, Katrhryn Reed in Tuscon, the USA and Beryl
Benacerraf in Harvard, the USA [Woo J., 2001]. In Latvia this field started
developing much later - fetal cardiology at the Latvian State Children's
Cardiology Centre was begun at the end of 1997 [Zīdere V., Lācis A., 1998}.
One of the tasks of prenatal diagnostics is to identify a high risk pregnancy for
further referral to specialized centers. There exists a series of signs suggesting
a possible heart pathology in a fetus, however, the majority of pregnant women
whose fetus has the heart disease does not go into any group at risk [Allan
L.D., 2000], About 30% of severe, complicated pathologies are detected in a
four-chamber position, though the latest studies [Copel J.A. et al., 1997; Darla
B. et al., 1998] have proved that if the attention is paid to the edema of the
neck fold in 10-14 gestation week and later, by referring the woman to a
specialist, it exceeds 50% [Allan L.D.,2000; Ghi T. et al., 2001, Zosmer N. et
al, 1999]. With diagnostic possibilities improving, ultrasonoscopy is occupying
the leading role in prenatal diagnostics. High-tech digital echocardiographs
are being used in specialized centers for the examination of the heart, thus
giving a chance to identify severe, combined heart pathologies already at the
end of the first trimester and at the beginning of the second trimester [Huggon
I.C. et al., 2002].
If to compare the situation with the period 20 years ago, the surgical tactics has
greatly changed in the treatment of heart diseases from palliative to the radical
one, for example, tetralogy of Fallot, as well as previously untreatable surgical
cases are offered a surgical intervention now, for example, hypoplastic left
heart syndrome. Major emphasis has lately been put on the verification of
heart diseases as early as possible [Allan L.D., 2003; Huggon I.C. et al, 2002;
Stoll C. et al., 2002]. Consequently, it is extremely important to render
professional and adequate treatment taking into account the child's age and
the type of a heart disease. Fetuses with congenital heart disease, whose systemic
or pulmonary circulation after birth depends on the function of the arterial
duct, labour is recommended in medical institutions which are close by the
children cardiology centers and which can provide a child cardiologist's care
when introducing a controlled prostaglandin input, artificial lung ventilation,
and if necessary, invasive treatment (ballon atrial septostomy) and in case of
need, a surgical correction, thus decreasing the neonatal mortality [Allan L.D.,
2000; Berghella V. et al, 2001; Brick H.D. et al., 2002; Gembruch U., Meberg
A., 2002], Considering the birth rate in Latvia of late, each year about 200
neonates are born with congenital heart diseases, therefore children cardiology
takes an important part in the children health care [LacisA., ZTdere V., 2000],
Results of diagnostics of congenital heart diseases much depend on the doctor
whose responsibility is pregnancy care, as well as ultrasonography specialist.
Therefore, lagging behind in more than 15 years from the leading European
children cardiology clinics, the first prenatal cardiology centre in Latvia was
established at the end of 1997, starting a close collaboration with the State
Medical Genetics Centre and gynaecologists in all regions of Latvia. In parallel
to theoretical lectures in the post-diploma training courses at Riga Stradini
University, the gynaecologists acquire the necessary skills for a successful fetal
heart examination by ultrasonograph at the Latvian State Children's Cardiology
Centre which are in line with AEPC recommendations. Jointly with Latvian
Association of Children Cardiologists and Latvian Association of
Gynaecologists and Obstetricians, there have been written methodical guidelines
on fetal heart ultrasonographic examination [Zīdere V. et al., 2003], Both social
and psychological aspects are important, the news on a sick child being born,
brings unexpected changes in the family. Timely and detailed information on
the expected child having a congenital heart disease may give a chance to
parents to prepare and to plan for the future, including the interruption of
pregnancy, considering the fact that prognosis in each heart disease case and
its treatment process is different [Allan L.D., 2000; Berghella V. et al., 2001;
Brick H.D. et al., 2002; Gembruch U., Meberg A., 2002].
Topicality of the study
Quite commonly the diagnosis of congenital heart disease at early neonatal
period is hard to perform if not done by a children cardiologist, or if no
indications are found prenatally on heart pathology. As a result, there may be a
risk not to render timely professional assistance, thus increasing possibilities
for a potentially unfavorable disease outcome [AEPC, 2003].
Aim of the study was to do a prospective research in diagnostics of prenatal
heart diseases in Latvia thus facilitating the improvement of prenatal care.
The following objectives were undertaken:
1. To perform fetal echocardiograms in not less than 2000 pregnant women
within the period from 15 gestation week till the end of gestation.
2. To perform fetal echocardiograms both on those pregnant women who belong
to congenital heart pathology risk group and on those who are outside it.
3. To do the study by making use of echocardiograph, fetal heart program,
two-dimension, M-mode, spectral and color flow mapping.
4. To video-record all the documented tests, providing a good retrospective
analysis, if it is needed, and to document the data of case histories which
characterize the possible risk group for congenital heart pathology.
5. To classify the identified heart pathologies into three main groups, such as,
non-structural heart pathology, structural heart pathology and cardiac rhythm
disorders. To analyze the results of each of the main classified cardiac
pathology groups in detail.
6. For statistical model analysis: SPSS program, descriptive and conclusive
statistical methods to be used.
Novelty of research.
For the first time a research was done in Latvia describing the picture of the
present situation in diagnostics of prenatal heart diseases in the countryPractical application of research.
Taking into account the significance of heart pathologies, their role in children
pathology and neonatal care, there is a chance to provide a timely patients'
care in a specialized centre. When obtaining grounded information on the
problem mentioned, one can introduce the educational programs to students
and doctors, thus promoting the improvement of medical care quality.
Theses suggested for defense:
1. Congenital heart pathology in Latvia is a very common fetal anomaly.
2. During pregnancy it is possible to diagnose a wide spectre congenital heart
pathologies by echocardiographic examination.
3. Timely diagnosed heart pathology in a fetus allows rendering an adequate
medical assistance by decreasing the neonatal lethality in the country.
4. Timely diagnosed heart pathology in a fetus allows the family to choose
the most suitable treatment tactics.
Structure of promotion work: The paper includes 10 chapters: introduction;
literature survey; 5 chapters describing the process of research; discussion of
results; conclusions; practical recommendations and references.
Supervisor of research: Habif. Doctor of Medicine, Professor Aris Lācis Riga
Stradini University Children Cardiology clinic, the Latvian State Children's
Cardiology Centre.
Research consultant: Doctor of Medicine, Professor Lindsey D Allan, Harris
Birthright Centre for Fetal Medicine Research, King's College Hospital,
London, UK.
Research process.
The research was done at Riga StradinS University Children's Cardiology clinic,
the Latvian State Children Cardiology Centre (head- Habil. Doctor of Medicine,
professor Aris Lācis) in the period from January 1, 1998 till April 30, 2003.
PUBLICATIONS IN QUOTED SCIENTIFIC
EDITIONS ON RESEARCH THEME
1.
2.
D.J. Better, H.D. Apfel, V. ZTdere, L. D. Allan. Pattern of pulmonary
venous blood flow in the hypoplastic left heart syndrome in the fetus.
Heart, 1999;81:646-649.
V. Zidere, I. Lubaua, A. Lacis. Giant fibroma of the right ventricle.
Cardiol Young 2002; 12:584-586.
3.
4.
5.
6.
7.
V. Zīdere, I. Lubaua, A. Lacis. Pirmo četru prenatālās kardioloģijas
gadu rezultāti Latvijā. ZRaksti /LMA 2002:68-71.
I. Lubaua, V. Zīdere, A. Lācis. Transtorakālās ehokardiogrāfijas
metodes pielietojums koronāro artēriju patoloģiju diagnosticēšanā
bērniem. ZRaksti /LMA, 2002:65-67.
E. Lubaua, V. Zidere, A. Lacis. The Roie of Transoesophagal
Echocardography During Repair of Multiple Congenital Coronary
Artery Fistulas. Acta medica Lituanica. 2003; 4:189-192.
A. Lācis, L. Šmits, V. Zīdere, I. Lubaua, 1. Lāce, J. Auziņš, Z. Straume.
Kambaru starpsienas defekta slēgšana mākslīgās asinsrites apstākļos
pirmajā dzīves gadā. Latvijas ķirurģijas žurnāls. 2003; 3: 88-93.
Vita Zīdere. Rekomendācijas augļa sirds ultrasonogrāfiskajai
izmeklēšanai. 2003. ISBN 9984-19-402-7.
Presentations at scientific conferences on the research theme.
1.
2.
3.
4.
5.
Zīdere V., Lācis A. Pirmais prenatālās kardioloģijas gads Latvijā.
Publicēts tēžu krājumā: I Latviešu sieviešu slimību un dzemdību
speciālistu kongress. Rīga, Latvija, 1999: 66. lpp.
Zīdere V., Ezeriņa D. First tree yearexperience in prenatal cardiologv
in Latvia. Published in abstract book: The VIII Baltie Sea Conference
on Obstetrics and Gynecology, Riga, Latvia, 2001.
V. Zidere, LD Allan, A. Lacis. Initial four-year experience in prenatal
Cardiology in Latvia. First Baltie States Conference on Ultrasound
in Obstetrics and Gynecology. Vilnius, Lithuania, 2002: p. 14.
Lācis, M. Jagmanis, V, Zidere, Z. Garleja, J. Auzins, I. Vanaga, Preisa,
I. Lace, L. Smits. A case of organising the special paediatric cardiac
centrēs: improved surgical outeomes at the Latvian State Cardiology
Centrē for Children. Published in abstract book: 3rd World
Congress of Pediatric Cardiology and Cardiac Surgerv, Toronto,
Canada, 2001: 881pp. un Published in abstract book: 25
World
Congress of the International Society for Cardiovascular Surgery.
Cancun, Mexico, Cardiovascular Surgery Published in journal of
Cardiovascular Surgery, 2001:9, p.89.
V. Zidere, I. Lace, A. Lacis. Non-invasive echocardiogrphic diagnostics
of congenital heart defeets for children before and after surgery in
The Latvian State Cardiolgy Center for Children. 25 World Congress
of the International Society for Cardiovascular Surgery. Cancun,
Mexico. Published in journal of Cardiovascular Surgery, 2001:9,p.92.
6.
7.
8.
V. Zīdere, I. Lubaua, L. Allan, A. Lācis. Pašreizējā prenatala iedzimtu
sirdskaišu diagnostika Latvijā. Publicēts tēžu krājumā: 2002.gada
Medicīnas nozares zinatniskā konference. Rīga, Latvija, 431pp.
J.Bars, I. Kalke, A.Lapsa, V. Zidere, I. Grivina. Prenatal US markers
of fetal cromosomal abnormalities. Published in abstract book: First
Baltic States Conference on Ultrasound in Obstetrics and Gynecology.
Vilnius, Lithuania, 2000: p. 21
I. Lubaua, V. Zidere, A. Lacis. Congenital coronary artery fistulas in
children: diagnosis, surgical technique and results. A Marcus
Wallenberg International Symposium: The coronary Arteries in
Children Anatomy, Flow and Function. Lund, Sweden, 2003.
LITERATURE SURVEY
Epidemiology of congenital heart diseases
The incidence of congenital heart diseases vary according to the investigation
methods, i.e. from four to eleven cases per 1000 live borns [Allan L.D., 2000;
Buskens E. et al., 1996; McGahan J.P., 1991; Stumpfen I. et al., 1996]. A.
Meberg's (2002) study shows that in some regions the incidence of heart
diseases is even lower, for example, 3-5% in Norway where ultrasonographic
diagnosing of fetal pathology in the second gestation trimester is not the primary
task, but it may be high in the countries or regional centres where pathology
diagnosis during pregnancy, especially in the second trimester, are included in
the special purpose program, for example, London, England [Brick H.D. et al,
2002; Gill H.K. et al., 2003].. Looking through the data on the Baltic States'
region, one can conclude that medical care in children cardiology and cardio
surgery in each of the Baltic States is organized in a different way. In Latvia
the medical care in children cardiology, including fetal cardiology, is organized
according to the guidelines of Association for European Paediatric Cardiology.
Such a prenatal cardiology care is considered an optimal one which provides
concurrent access to specialists who are potentially involved in a child care
just after birth, i.e., pediatric cardiologist-neonatologist, pediatric cardio surgeon
and geneticist, who are available in the Latvian Sate Children's Cardiology
Centre [Zīdere V, et al., 2002].
Pathogenesis of congenital heart disease
Etiology of congenital heart disease
The heart is a complex organ, however, already in the fifth week after the
last menstruation (in the third week after conception) it is developed. Complete
septation is accomplished at about the 8 week after the ovulation, the time
when atrioventricular septal defect is about to develop, it never disappears and
does not regress spontaneously. And still trabecular transformation in the right
and left ventricles, as well as complete development of atrioventricular and
semilunar valves is continuing up to the 14 -16 gestation week. [Gittenbergerde Groot A.C. et al., 2000]. However, some pathologies may progress all through
the pregnancy time or may be exposed in its various periods. As the most
characteristic ones are - valvular stenosis, right or left chamber hypoplasia,
tumours.
Classification of pathogenesis according to Clark:
I Ectomesenchvmal tissue migrations abnormalities
- conotruncal septation defects, for example, tetralogy of Fallot;
- brachial arch defects, for example, double aortic arch
- abnormal conotruncal cushion position, D-transposition
II Abnormalities of intracardiac blood flow
- left heart defects, for example, hypoplastic left heart;
- right heart defects, for example, pulmonary valve stenosis;
- perimembranous ventricular septal defect
III Cell death abnormalities, for example, muscular VSD.
IV Extracellular matrix abnormalities, for example, AVSD.
V Abnormal target growth, for example, cor triatriatum
VIAbnormal situs and looping: situs inversus totalis; heterotaxy;
looping abnormalities, for example, L-transposition of the great arteries.
Reasons of congenital heart diseases are often unknown, in single cases this
risk can be prognosed prior to pregnancy, however, most often pathology is
diagnosed during pregnancy [Allan L.D., 2000]. A great number of authors
speak about three big risk groups: "maternal", "familial" and "fetal" [Allan
L.D., 1986;JeantyP.,PiIuG., 1999]
"Maternal" risk factors
Metabolic disorders
- diabetes meilitus for a mother may be the cause of a fetal hyperinsulinaemia,
and as a result, there may develop a transient form of hypertrophic
cardiomyopthy, as well as macrosomy and hypoglycaemia for a fetus. The
question of gestational diabetes is controversial. Diabetes increases the risk
of congenital heart disease up to 4 - 5 times. [Allan L.D. et al., 2000; Cooper
M.J. et al., 1992; Wong S.F. et al., 2002].
- phenylketonuria may be the cause for tetralogy of Fallot, left heart obstructive
lesions or VSD [Allan L.D. et al., 2000; Rouse B. et al., 2000].
Influence of teratogenous factors
Maternal exposure to drugs up to 61 -8l' gestation week, the active substances
of which contain valproic acid (anticonvulsants), epanutin, retinoic acid and
lithium, and may cause severe fetal heart disorders, which most commonly are
severe and combined heart diseases [Angelini P., 1995]. The use of NSA1D
after 25 -30 gestation week may be the reason for a postnatal right chamber
and pulmonary hypertensions in newborns, as well as the closure of arterial
duct prenatally. [Benettoni A. et al., 2002]. The effect of alcohol toxicity on
fetus is well known, though the view of being a risk factor for a congenital
heart disease is controversial. Maternal infection with rubella virus by the 12
gestation week is the reason of the development of pulmonary artery stenosis
in fetus. Cytomegalovirus, coxackie, parvovirus, mumps and toxoplasmosis
infection during pregnancy are the reasons for cardiac anomalies [Allan L.D.,
2002; Jeanty P., 1996;].
Mothers with autoantibodies
In cases of mother's autoimmune diseases (such as lupus erythmatosus), fetus
may likely develop atrioventricular block, cardiomyopathy and fibroelastosis.
In about 70-80% of fetuses with an antibody-induced atrioventricular block,
mothers are asymptomatic without a diagnosis of autoimmune disease
[Askanase A.D.et al.,1998; Brucato A.et al., 2003].
Congenital heart disease in mother and familial cardiomyopathy
Depending on mother's heart disease type, excluding any genetic pathology, a
fetus congenital heart disease risk ranges even by >12%, Table 2. In majority
of cases, cardiomyopathies are secondary, however, fetal echocardiography is
recommended [Allan L.D., 2000; Jeanty P., 1996].
Mother's age over 35 years
Mother's age over 35 years is not considered a specific risk factor for congenital
heart disease in a fetus, and still, there is an increased risk for a genetic pathology.
To exclude the risk for heart disease, the fetal heart ultrasonographic
examination is recommended to be done at a specialized centre [Allan L.D.,
2000].
"Familial" risk factors
Previous child or fetus with congenital heart disease or congenital
atrioventricular block
The risk to have heart pathology repeated in the family is inconsistent and it
depends on the heart disease type in the family history. Every other individual
in the family may have just the same heart pathology like the previous child or
fetus, or quite a different congenital heart disease. If the previous child is having
a heart disease, then the next one may have a risk to be born with congenital
heart disease by 2%, however, if two children in the family are having CHD,
then the risk increases up to 10%, as depicted in Table 1.
Table 1. reccurence risks for congenital heart defects in siblings.
(Reproduced from Nora &Nora, 1988.)
Defect
I sibling
affected
Ventricular septal defect
3%
Patent ductus arteriosus
3%
Atrial septal defect
2,5 %
Tetralogy of Fallot
2,5 %
Pulmonary stenosis
2%
Coarctation of aorta
2%
Aortic stenosis
2%
Transposition of great arteries
1,5%
Endocardial cushion defects
3%
Fibroelastosis
4%
Hypoplastic left heart
2%
Tricuspid atresia
1%
Ebstein anomaly
1%
Truncus arteriosus
1%
Puimonaru atresia
1%
2 siblings
affected
10%
10%
8%
8%
6%
6%
6%
5%
10%
12%
6%
3%
3%
3%
3%
Congenital heart disease in parents
The risk when one of the parents has a congenital heart disease varies between
5% to 10%, depending on the type of heart disease.
Table 2. Reccurence risks for congenital heart defects in offspring given one
affected parent. (Reproduced from Nora &Nora, 1988.)
Defect
Aortic stenosis
Atrial septal defects
Atrioventricular septa! defect
Coarctation of aorta
Patent ductus arteriosus
Pulmonary stenosis
Tetralogy of Faliot
Ventricular septal defect
Father affected Mother affected
3%
1,5%
1%
2%
2,5 %
2%
1,5%
2%
13-18 %
4-4,5 %
14%
4%
3,5-4 %
4-6,5 %
2,5 %
6-10%
Chromosomal anomalies, single-gene disoders or syndrome with
congenital heart disease or cardiomyopathy.
Single-gene disorders in the family history in one or both parents increases
the risk for a single gene defect in a fetus, resulting in congenital heart disease
or cardiomyopathy from 25% to 50%. The most common single gene disoders
are typical with Marfan, Noonan, Holt-Oram, DiGeorge, velofacial, Williams
syndromes [Angelini P.,1995; Lacro R., 2000].
"Fetal" risk factors
Extracardiac anomalies
Results of the studies done allow to draw conclusions: if there exists more than
one organ system malformation, the risk of genetic pathology is greater.
P.Jeanty's study (1996) proves that heart anomalies are associated with
extracardiac anomalies in 5-10% cases, while fetuses with extracardiac
pathologies are found to have heart diseases in 7-17% cases. Most commonly
cardiac anomalies are combined with: omphalocele, diaphragmatic hernia,
nuchal edema, duodenal atresia, tracheo-oesophagealfistula, cystic hygroma,
skeletal anomalies and also retardation in fetus growth.
Fetal hydrops or polyhydramnios are considered as a complication for the
existing baseline pathologies, which in 25% cases are of cardiac type. The
most common reasons are disorders of the heart rhythm, a series of structural
heart pathologies, such as atrioventricular septal defect, coarctation of aorta,
cardiomyopathies, and tumours.
Oligohydramnios is not a typical finding in case of congenital heart disease;
however, it may likely develop if intrauterine infection is present.
Echogenic cardiac focus. Results of extended studies demonstrate that if
echogenic cardiac foci exists as an isolated finding, it can be considered as a
trisomy 21 marker in correlation to mother's age and the first semester screening
test [Huggon I.C.et al., 2001].
Arrhythmias. Disorders of heart rhythm in a fetus in the last ten gestation
weeks, manifested by ectopic beats, both atrial and ventricular, are more of a
functional type, however about 2% cases correlate to a structural heart
pathology. Certainly, a detailed heart examination is needed, and also the
evaluation of hemodynamic status in case of sustained bradychardia and
tachycardia [Hata T. et ai., 1988; Hess D.B. et al., 1998; Groves A.M. et al,
1996; Rosenthal E., 2000; Simpson J., 2000].
Genetic pathology in a fetus with heart disease is common in >20% cases. If
more than two fetal pathologies exist, there is a greater risk for a genetic
syndrome. Majority of syndromes are diagnosed relying on the clinical picture
after birth [Fasnacht M.S. et al.,2001; Hess D.B., 1998; Lacro R., 2000].
Heart pathology correlates to:
-autosomal recessive syndromes, for example, Ellis- Van Creveld;
-autosomal dominant syndromes, for example, Marfan;
-X-linked recessive syndromes, for example, Dreifuss;
-chromosomal aneuploidies, for example, trisomy 21, trisomy 18, trisomy
13, and 22q deletion.
Examination method
Echocardiography is the only visual diagnostic method in the diagnostics of
structural heart pathologies, heart rhythm and hemodynamic disorders [Eronen
M.1997], It is a non-invasive, painless ultrasonographic method. In order to
ensure a maximum good examination quality and proper observation of a
pregnant woman and a fetus further on, The fetal Working group of AEPC,
2003, recommends to do a detailed fetal heart examination by a child
cardiologist with an extra specialization in fetal cardiology and at a children
cardiology unit. It is absolutely necessary to have a close cooperation with
genetics unit, paediatric cardiothoracic surgical unit, specialists in obstetrics
and gynaecology, and neonatal unit [Carvaiho J.S. et al., 2002; Fasnacht M.S.
eta!., 2001; HafnerE. etal., 1998]. For fetal heart examination there is used
similar echocardiographic equipment as in children cardiology [AEPC, 2003;
Gembruch U., 1997], i.e., 5 MHz and 3,5 MHz transducers. High resolution
equipment allows earlier and more accurate diagnosis and a special fetal
heart programme improves examination quality. During examination one
should use B-mode, M-mode, PW and CW Doppler, colour flow imaging.
Systematic normal and pathological heart examination in real time using
ultrasonographic method was first described by Lindsey Allan (Guy's hospital,
London) in 1980.
Fetal heart echocardiographic examination is possible already starting from
the end of the first trimester of pregnancy and the beginning of the second
trimester, i.e. from 12-14 gestation week till its end. [Allan L.D., 2003;
Huggon I.C. et al., 2002]. It is considered that in a routine ultrasonographic
examination a complete heart analysis can be acquired in 18 gestation weeks,
however in high-risk cases this examination is recommended starting from
14th-16th gestation week [Allan L.D., 2003]. On the basis of studies on a
possibility of correlation of congenital heart pathology with genetic pathology,
it is recommended to have a doctor-genetician's consultation to determine the
probable amniocentesis and the caryotype, depending on the diagnosis and the
time of pregnancy [Chaoi R.et al., 1999].
Results of diagnosed congenital heart diseases in utero
Antenatal diagnostics of those pathologies, which can be recognized in fourchamber position, is still insufficient. Although the diagnosed heart disease
spectre is increasing with time, the graver pathologies, however, are diagnosed
postnatally, therefore any heart disease diagnosed in a fetus during pregnancy,
is important, in this way getting a more precise idea about this period [Allan
L.D., 2000; Ott W.J., 1995; Strauss A.et al., 2001].
A comparative study by D.H. Brick and L.D. Allan (2000) between London,
Yale and Newhaven shows that both atrioventricular septal defect and
hypoplastic heart syndrome can be diagnosed in four chamber position, and
are seen antenatally twice as often than postnatally. On the contrary,
transposition of great arteries which can be diagnosed by examining only major
blood vessels is seen twice as often postnatally as during pregnancy. S. Levi
study (1998) proves that about 98% of pregnant women are examined
ultrasonographically in most of European countries. One should emphasize
the professional skills of medical specialists while doing fetal heart
ultrasonographic examination [Erenius K.et al., 1999; Stoll C.et al., 2001].
Studies covering a longer time period show that a complete heart examination
in routine fetal investigation can give maximum results. By adding great arteries
views to the traditional four- chamber view, the diagnosis of combined, severe
heart diseases increases from 60% to 90% [Allan L.D., 2000; Carvalho J.S. et
ai., 2002]. Diagnostic spectre is influenced by the fact that even >55%
pregnancies with prenatally diagnosed heart diseases are terminated [Brick
H.D.et al., 2002; Stoll C.et al., 2002]. Despite the fact that the surgical correction
possibilities, invasive cardiology and newborn intensive therapy level have
increased in the last twenty years, the long-term survival of those pregnancies
that are continued after making a prenatal heart disease diagnosis is about
60% [Brick H.D.et al., 2002].
General characteristics of patients
Material
From January 1,1999 till April 30, 2003,at the State Children's Cardiology
Centre and outpatient clinic "ARS", 2445 fetal echocardiograms were done
on mother, aged from 16-50 years (mean age 26,85+7,56 years), including 21
twin and 1 triplet pregnancies from 14-41 (on average in 28,23±6,72 gestation
week) gestation week. Retrospective detailed clinical study includes 225
echocardiograms of pathological findings from 15-41 gestation week in mother
at the age of 17-50 years. Fetal echocardiography was done by a peadiatric
cardiologist with an extra training in fetal cardinlogy.
Selection of patients
A mother was referred to fetal echocardiography by a doctor who was following
up the pregnancy course (a gynaecologist, in rare cases a family doctor, in
single cases - a midwife) or an ultrasonography specialists, doctor-genetician,
taking into account the indications for an increased risk of heart disease, or in
cases when the examination of the heart was difficult to do in a routine obstetric
ultrasonographic examination, or this was the wish of a parents, not being in a
group at risk. Mother were referred to do a fetal echocardiogram considering
the following indications:
maternal indications: maternal metabolic disorders, maternal exposure
to cardiac teratogens, maternal collagen disease, maternal congenital heart
disease, age over 35 years;
familial indications: a congenital heart disease in a previous child or fetus,
paternal congenital heart disease, paternal chromolsomal anomalies, gene
disoders or syndromes (Noonan, Mar/an, Holt-Oram, DiGeorge syndrome,
etc);
fetal indications: fetal hydrops, any extracardiac, including, genetic,
pathology, any arrhythmia, polyhydramnios, echogenic cardiac focus,
suspicion of cardiac malformation or disease during obstettrical scan.
Methods
Fetal cardiology methods
Investigation was done by a certified pediatric cardiologist with extra
specialization in fetal cardiology. Fetal heart was examined by using two
dimensional (2D) guided, pulse, and continuous wave Doppler
echocardiography equipment (Hewlett PackardSonoss 4500, Accuson Aspen
and ATL 5000) with a 5-3 MHz transducer, in separate cases 7 and 8 MHz and
2-3 MHz, fetal heart programme. All examinations were performed via
transabdominal access.
Examination was standardized and in all cases the following investigation
positions were used: 2D- five projections were used: four chamber position;
five chamber position, long axis, short axis, and arch views. To make the
study precise and investigations in all fetal echocardiography cases
qualitative, the following parameters were assessed: heart rhythm; situs; heart
size in relation to thorax; atrial and ventricular chambers; valves;
atrioventricular junctions (Figure 1); aortic and ducta! arch.
Figure 1. Four chamber position.
In all investigations the colour Doppler was used, pulse wave and continuous
wave dopplerography in those cases when a pathology was suspected. Heart
rhythm disorders, the type of arrhythmias were analyzed by using M-mode at
atrial and ventricular level.
All pathological investigations were divided into three large groups: structural
heart pathology; non-structural heart pathology; heart rhythm disorders.
All investigations were recorded in a video having a potential to analyze
them repeatedly in case of need. Each pregnant woman's personal data were
registered. After the examination of fetal heart the mother returned back to the
doctor who was following up the pregnancy in the medical institution were the
woman was signed up.
When pathology was diagnosed, the consultation at the genetician's was advised,
if a neonate's ondition after birth had been prognosed as severe, pregnancy
was recommended to be followed up at Riga Stradini University hospital,
Perinatoiogy Centre, where the further neonatal care was done at the Perinatal
Centre and /or the newborn was transported to the State Children's hospital
"Gailezers" for further treatment. In all those cases where heart pathology had
been diagnosed during pregnancy, and in those cases where there was a suspicion
for heart pathology only after birth, the recommendations were given to do
observation in dynamics after birth at the Latvian State Children's Cardiology
Centre. In about 90% cases the information was acquired about the postnatal
outcome.
Statistical data processing
The data acquired were entered into computer and processed by SPSS
programme using generally approved descriptive statistical methods. For
proportion evaluation the Wilson's method of Confidence Interval Analysis
was used. R.G. Newcombe and D.G. Altman say that the traditional method
for calculation of proportions' standard error (SEp) can be applied to normally
or almost normally distributed data and it is calculated by means of the equation
where p is the probability of the direct event and r— scope of selection. The
lower and upper border of population 95% confidence interval is estimated by
the formulas
In the Wilson's method, recommended by the above-mentioned authors, first
of
all
the
values
are
estimated
A = 2r +1,96 2 ;
where m is the number of beneficial events and n -scope of selection. After
that are calculated
95% confidence interval borders from
In our work we
used Wilson's method, recommended by the above-mentioned authors, since
it can be used for processing of any data, despite their distribution. Calculations
were done by Altman's specialized computer programme CIA (series Nr.:
CYK216C) worked out in the year 2000.
RESULTS
Within a period of five years and four months 2445 investigations were done.
Each year there is seen an increase of the total number of examinations and the
increase of the number of pathological examinations (Table 3). 92% of the
total number of examinations demonstrates pathological findings. From them
in 105 (46,7%) cases, fetuses are with structural heart pathology, 62 (27,6%)nonstructural heart pathology and 58 (25,8%)- heart rhythm disorders.
Table 3. The number of total and pathological examinations, distribution
according to the years during which the clinical study was done.
Year
1998 1999
2000 2001
2002 2003IV
Total
135
131
356
560
764
499
Pathology
4
16
34
62
66
44
Pathology, % 3,0% 12,2% 9,6% 11,1% 8,6% 8,8%
By analyzing the pregnancy period in which fetal heart pathology was diagnosed
during fetal echocardiography, a conclusion can be drawn that in 68,8% cases
this examination is performed after the 22nd gestation week and in 31,2%
cases up to the 22nd pregnancy week including. Fetal hearts with a nonstructural
heart pathology were examined by special methods in the period up to the
22nd gestation week in 48,4% (30/62) cases, structural heart pathology up to
this pregnancy time were found in 22,9% (24/105) cases, in the group of heart
rhythm disorders 27,6% (16/58). Mothers up to the age of 35 years were 86,7%
(195/225) cases, 10,2% (23/225) between 35 and 40 years and in 3,1% (7/
225) were older than 45 years.
Structural heart diseases was seen in 13,3% (14/105) mothers at the age of
35 years, non-structural in 14,5% (9/62) cases and heart rhythm disorders in
12,1% (7/58) cases at this age group.
Family and maternal history as a possible risk factor are seen in 7,6% (17/
225) cases (Table 4), from them 29,4% (5/17) cases in a non-structural heart
pathology group, 5/17 (29,4%) structural heart pathologies and 2/17 (11,8%)
in the group of heart rhythm disorders (Table 5).
Table 4. Prevalence of family and maternal history incidence in Latvian
women assigned to the study.
By adding, that VI, VII and VIII are considered as a relative marker for fetal
heart disease.
Table 5. Correlation of family and maternal history with heart pathology groups.
Table 6. Distribution of prevalence of codiagnoses (n=225).
Codiagnosis
In 25,3% cases (57/225) of pathological heart examinations there were found
a codiagnosis in a fetus which may correlate with the existing heart pathology
(Table 6), from them 47,4% (27/57) cases in a nonstructural heart pathology
group, 43,9% (25/57) structural heart pathologies and 8,8%(5/57) in the group
of heart rhythm disorders (Table 7).
Echogenic cardiac focus are not defined and analyzed separately as an isolated
pathology, it is considered more like a marker. About 5,3% (12/225) cases
from all pathological investigations are combined with this finding. By
displaying the more severe forms, one can see that in two cases with the
diagnosis ,,golf balls", a gynaecologist indicates echocardiogram to fetuses
with a grave, combined heart disease - hypoplastic left heart syndrome.
Echogenic cardiac focus and extra beats have been the reason for a paediatric
cardiologist's consultation in two more severe heart disease cases transposition of great arteries.
Table 7. Prevalence of codiagnoses in groups of heart pathologies.
Group
Codiagnosis
N
%
95% TI
Lo.
I
II
III
Nonstructural heart pathology (n=62)
Diafragmatic hernia
8
Oligohydramnios
5
Polyhydramnios
4
Hydronephrosis
2
MDA
2
Feto-fetal transfusion
2
IUGR
1
Oesophagal atresia
I
Intestinal anomalies
1
Lung cysts
1
Structural heart pathology (n = 105)
IUGR
6
MDA
5
Polyhydramnios
5
Diafragmatic hernia
2
Hydronephrosis
2
Hydrops fetalis
2
Hydrothorax
1
Hand anomalies
1
Oligohydramnios
1
Rhythm disorders (n = 58)
IUGR
2
Hemodinamic disoders
1
Oligohydramnios
1
Polyhydramnios
1
Up.
12,9%
8,1%
6,4%
3,2%
3,2%
3,2%
1,6%
1,6%
1,6%
1,6%
6,7%
3,5%
2,5%
0,9%
0,9%
0,9%
0,3%
0,3%
0,3%
0,3%
23,4%
17,5%
15,4%
11,0%
11,0%
11,0%
8,6%
8,6%
8,6%
8,6%
5,7%
4,8%
4,8%
1,9%
1,9%
1,9%
1,0%
1,0%
1,0%
2,6%
2,1%
2,1%
0,5%
0,5%
0,5%
0,2%
0,2%
0,2%
11,9%
10,7%
10,7%
6,7%
6,7%
6,7%
5,2%
5,2%
5,2%
3,4%
1,7%
1,7%
1,7%
1,0%
0,3%
0,3%
0,3%
11,7%
9,1%
9,1 %
9,1%
Abbreviations: IUGR-intrauterine growth retardation; MDA- multiple
developmental anomalies
Genetic pathology
The caryotype was defined during pregnancy in 18,2% (41/225) cases from
the number of pathological investigations, from them a normal caryotype answer
was received 43,9% (18/41) and pathological caryotype was found in 46,3%
(19/41), in four cases there was seen a genetic syndrome shortly after birth. In
general, genetic pathology both prenatally and postnatally was 10,2% (23/
225). It can be seen in Table 8. Comparing the incidence of heart pathologies
in mother at the age under 35 years, with that of mother from 35 years, it was
found that the older are the mother, the greater probability for the development
of a fetal heart pathology OR (odds ratio)= 3,40 (95% confidence interval
from 1,13 to 10,06).
Distribution in these age groups was tested by Fisher's chi square test and by
using Yates correction, it was found that this distribution is statistically confident
variable (c2 - 4,94, p = 0,026).
Table 8. Prevalence of genetic pathology (n=225)
Nr. Genetic pathology
N
%
95% TI
Lo.
Up.
8
3,6%
1,8%
6,9%
1. trisomyl8
2. trisomy 21
7
3,1%
1,5%
6,3%
3. trisomyB
2
0,9%
0,2%
3,2%
4. 22qll deletion
1
0,4%
0,1%
2,5%
5. 47+M
I
0,4%
0,1%
2,5%
6. Syndromes:
- Dandy Walker
1
0,4%
0,1%
2,5%
- Goldenhar
1
0,4%
0,1%
2,5%
- Ivemark
1
0,4%
0,1%
2,5%
- Cornelia de Lange
1
0,4%
0,1%
2,5%
7. Normal caryotype
18
8,0%
5,1%
12,3%
Nonstructural heart pathologies
In 3,2% (2/62) cases aortic valve regurgitation was described by
dopplerography during pregnancy as little expressed or moderately expressed
and not correlating to structural heart pathology. In one of these cases the firstdegree relatives had congenital heart disease in the family history. There are
no data of pregnancy termination or need for treatment because of the heart
disease after birth.
Potential stenosis of aortal valve - abnormal spectral Doppler measurements
in the ascending aorta were seen in 3,2% (2/62) cases, however, in both cases
after birth the echocardiographic examination was without any pathological
finding and specific therapy was not needed.
Hemodynamic disorders, which are characterized by pathological Doppler
measurements at ductus arteriosus and ductus venosus level in 12,9% (8/62)
cases.
Diaphragmatic hernia in 62,5% (5/8) cases, cysts in lung tissues in 12,5% (1/
8), oligohydramnios 12,5% (1/8) in a 37-years old mother and fetus grows
retardation 12,5% (1/8) where a mother is an active smoker. Pregnancy was
terminated in one case where a fetus was diagnosed diaphragmatic hernia.
Hypertrophic cardiomyopathy was seen in 9,7% (6/62) cases. In two of
them, the etiological factor - feto-fetal transfusion, in one case intrauterine
virus infection (cytomegalo, herpes simplex). An early neonate death was in
one case in a 38 years old woman whose fetus had hypertrophic cardiomyopathy
in combination with intestinal pathology. Pregnancy was terminated in 83,3%
(5/6).
Dilatation cardiomyopathy (DCMP) in utero was found in fetus in 8
cases from 62 (12,9%), figure 2.
Table 9. Correlation of dilatation cardiomyopathy with codiagnosis, prenatally diagnosed genetic pathology, family or maternal risk factor and
outcome.
Abbreviations: TOP - teermination of pregnancy; ND - no data
* maternal cytomegalo virus infection
Left superior veina cava is diagnosed in 1,6% (1/62) cases, this finding can
be explained as an anatomical specificity if it does not combine with a structural
heart pathology as it is in this case.
Mitral valve regurgitation (MVR) has been found in this study in 9,7%
(6/62) cases. In this group of heart diseases there are no data of
pregnancy termination or any specific heart disease treatment.
Tricuspid valve regurgitation, which Doppler during pregnancy had
been defined as moderate or severe and did not correlate with structural
heart pathology, were included into this study. In total, in 13 (21 %/62) cases
isolated tricuspid valve regurgitation was diagnosed. There are no data on of
pregnancy termination or the necessary treatment due to heart disease after
birth.
Situs inversus without heart pathology was seen in one case.
No other organ pathologies were diagnosed either. The existing findings can
be considered as anatomical specificity. The baby after birth is not under
observation of a paediatric cardiologist.
Figure 2. The 31st gestation week. Cross-section, four-chamber view.
Typical cardiomegaly, pericardia! effusion in a case of dilatation
cardiomyopathy.
Pericardia) effusion (>2 mm) was seen in 17,7% (11/62) cases of non-structural
heart pathologies. The reason for this finding in 9,0% (1/11) cases can be
considered as multiple development anomalies, hydronephrosis 9,0% (1/11).
Codiagnosis - polyhydramnios 27,2% (3/11) and oligohydramnios 9,0% (1/
II), the caryotype during pregnancy was determined in two cases; its result
was pathological in one - 21 chromosome trisomy. In three cases the maternal
age was over 35 years, in one case - over forty where the fetus was diagnosed
trisomy 2land poyhydramnios.
Formation - suspicion to possible neoplasm in this study was in 6,4% (4/62)
cases. Extracardiac formation in the lung was found in the third trimester in
one case and since it did not produce any hemodynamic problems and was
connected with lung tissues, there was no need for a paediatric cardiologist's
care. In one case both prenatally and postnatally were found a rudimentary
formation in the right atrium, which did not cause hemodynamic disorders and
the case is still under a paediatric cardiologists' care. Rudimentary formation
postnataily was confirmed also in the right ventricle. The only tumour —
rhabdomyosarcoma in the right ventricle was found in one case in the 32nd
gestation week which resulted in fetus mortus.
Heart rhythm disorders.
Such were 25,8% (58/225) cases. Up to the 22nd gestation week (including)
such disorders manifested in 27,6% (16/58) cases, however after the 30th
gestation week - 53.4% (31/58). In 12,1% (7/58), mothers are older than 35
years. In 8,6% (5/58) cases fetal arrhythmia correlate with oligohydramnios
(I), polyhydramnios (1), fetal growth retardation (2) and hemodynamic
disorders - pathological dopplerographic finding ductus venosus and ductus
arteriosus. In two cases the caryotype for a fetus was defined due to suspicion
for a possible genetic pathology (mother's age, changed alfa-fetoprotein level),
from them in one case - the 21 st chromosome trisomy. Heart pathology in a
mother - 1,7% (I), herpes simplex 1,7% (1) and cytomegalovirus 1,7% (1)
infection during pregnancy.
Premature contractions 84,5% (49/58). Basically functional arrhythmia which
were manifested after the 30th gestation week, from them in 96% cases there
was no need for a specific therapy either prenatally, or postnatally. The reason
for extrasystoles in 6.9% (4/58) cases can be considered extracardiac fetal
problems, such as oligohydramnios, polyhydramnios, hemodynamic disorders
and fetus growth retardation. However, in one case (1,7%) where the mothers
age was over 35 years, the fetus was found 21 chromosome trisomy up to the
22nd gestation week in diagnostic amniocentesis and pregnancy was interrupted.
Extra beats was combined with a structural heart pathology, such as TGA,
AVSD and complex heart diseases in 5,3% (12/225) cases. Supraventricular
tachycardia in 3,4% (2/58) cases appeared after the 35 th gestation week. Due
to hemodynamic disorders, pregnancies were interrupted by operative labour.
Both fetuses were successfully treated postnatally by using antiarrhythmics
therapy.
Sustained bradycardia (<100x') 5,2% (3/58). Complications during
pregnancy were not found in an either case, arrhythmias were not seen after
birth.
Tachycardia >170-180 times per minute with a tendency to remain for several
minutes was observed in 3,4% (2/58) cases. The reason may be the fetus growth
retardation in one case and in the second - cytomegalovirus infection. In both
cases no specific drug therapy for the treatment of heart rhythm disorders was
not applied, they spontaneously disappeared.
Congenital complete atrioventricular block was seen in one (1,7%) case in the
22nd gestation week, one of the most complex cases in the group of heart
rhythm disorders. Operative labour in the 36th gestation week, a successful
permanent epicardial paccemecer system implantation on the 5th day of birth.
Structural heart pathologies.
Structural heart pathology group 45,7% (105/225). This group was divided
into: 1) heart diseases which can be diagnosed in a four-chamber view; 2)
pathologies of great arteries.
Atrioventricular septal defect (AVSD) as an isolated pathology was diagnosed
in 7,6% (8/105) cases. Changes in chromosome number were found in 75%
(6/8) cases. Pregnancy was interrupted in 62,5% (5/8). Suspicion to heart disease
and the diagnosis verification at the Latvian State Children's Cardiology Centre
only after 30 gestation weeks is in 37,5% (3/8) cases, from them in two cases
(66,7%) -chromosomal pathology (Down syndrome and Edwards syndrome).
Unfavourable outcome in the first week - exitus letalis in one case (33,3%).
Table 10. AVSD correlation with codiagnosis, caryotype and outcome.
Diagnosis
(number)
Codiagnosis
prenatally
AVSD (I)
IUGR
AVSD(l)
IUGR
AVSD(l)
MDA
AVSD(l)
Polyhydranmios
AVSD (1)
AVSD (1)
Caryotype
prenatally
47 XX+18
Outcome
TOP
TOP
47 XX +21
TOP
Hydrothorax
47+M
TOP
Diaphragmatic hernia
47XY+18
EL
ND
47 XX+21
TOP
-AVSD(l)
47XY+21
PCo
-Abbreviations: EL - exitus letalis after birth; IUGR-intrauterine growth
retardation; TOP - termination of pre
gnancy; MDA- multiple development
anomalies; PCo PCo - under paediatric cardiologist's observation.
AVSD(l)
ASDI in this study was diagnosed in ]% (1/105) cases in a41-years old mother
in 20th gestation week, pregnancy was terminated, taking into account 13
chromosome trisomy (Patau's syndrome)as a result of amniocentesis.
Aortic valve stenosis in the study was diagnosed in 1% (1/105) cases. During
29 gestation weeks there were indications to a trivial aortic valve stenosis
which was progressing till the end of pregnancy. The newborn after birth was
not hospitalized in the Latvian State Children's Cardiology Centre and died on
the fifth day after birth due to a severe aortic valve stenosis.
Double outlet right ventricle makes 2,9% (3/105) from structural heart
pathology group, 66,7% (2/3) pregnancies are interrupted. In one case a father's
age might have been the etiological factor (67 years), in the second case Ivemark
syndrome was seen after birth.
Ebstein's anomaly was seen in 1,9% (2/105), a grave form in both cases,
recognized in the iast trimester. In one case - fetal hydrops and early neonatal's
death. In the second case - pulmonary artery hypoplasia, the infant after birth
was under paediatric cardiologist's observation.
Hypoplastic left heart syndrome. One of the most commoonly diagnosed
heart diseases in utero, including, four-chamber view. In the Latvian Sate
Children's Cardiology Centre 14 such cases have been diagnosed, 13,3% of
the total number of structural heart pathologies. Codiagnosis: fetal growth
retardation (1), congenital heart disease in the first degree relative (1), maternal
exposure to psychotrophic drugs in one case. Termination of pregnancy
occurred in 57,1% (8/14) cases, 35.7% (5/14) - an early neonatal death and
operative therapy in the first days after birth with a postoperative exitus letalis
in 7,1% (1/14) cases.
Complex heart disease (includes more than three malformations) is seen in
4,8% (5/105) cases. Fetal growth retardation is seen in one of them. Termination
of pregnancy in 60% (3/5). Two cases are still under paediatric cardiologist
observation. Genetic pathology - Goldenhar syndrome in one case was
diagnosed after birth.
Tetralogy of Fallot was diagnosed in 4,8% (5/105). As a codiagnosis for this
heart pathology there is oligohydramnios (1), diaphragmatic hernia (1) and
fetal hydrops (1). The caryotype prenatally was determined in 40% (2/5), from
them trisomy 18, diaphragmatic hernia ultrasonographically and pregnancy was
terminated (I). In total, termination of pregnancy in this group occurred in
40%, including one where a sibling had hypoplastic left heart syndrome.
Neonatal death after birth was in 20%( I /5) cases where the existing heart disease
was complicated by fetal hydrops.
Tricuspid valve atresia - 1,9% (2/105) cases. The caryotype was determined
in one case, however, despite its normal result, pregnancy was chosen to
interrupt because of a poor postnatal prognosis. Another case from this heart
disease group was diagnosed after 30th gestation week and it is still under a
children cardiologist's care.
Tricuspid valve dysplasia. One of the most severe heart diseases during
pregnancy which make up to 4,8% (5/105). The caryotype was diagnosed in
60% (3/5) cases, pathologic reponse was in one of them - 21 chromosome
trisomy in a mother aged over 35 years. Pregnancy was terminated in 80% (4/
5) cases. Fetus mortus in one case.
Tricusp and pulmonary valve stenosis - 1% (1/105). This heart disease is
combined with hydronephrosis and is diagnosed only in the last trimester and
ends with an early neaonatal death.
Ventricular septal defect (VSD) - 16,2% (17/105). Genetic pathology was
found in 35,3% (6/17), including prenatally 18 chromosome trisomy in 4 cases,
a fetus with multiple developmental anomalies in a 44 years old mother as one
of the cases.
Table 11. It demonstrates the correlation of ventricular septal defect with
codiagnosis, genetic pathology and outcome.
Diagnosis Codiagnosis
Caryotype
Genetic
Outcome
Abbreviations: EL - exitus letalis after birth, TOP- termination of
pregnancy, MDA- multiple development anomalies PCo - under paediatric
cardiologist's observation.
Muscular ventricular septal defect structural heart pathology which does
not cause any hemodynamic disorders. In this study - 29,5% (31 /105). Prenataly
the caryotype is defined in 2 cases (6,4%), one with a pathological result. As a
relative or doubtful risk factor might be donor's egg cell (after 1VF procedure)
in a 50 years old mother. In two cases, despite an insignificant muscular VSD
prenataly, a long-term hospital treatment under a cardiologist's observation
was needed. In one of them - a heart operation under cardiopulmonary bypass
at the age of three months due to a tumour (myxoma) in the right atrium, and in
another case also at the age of three months due to a viral etiology secondary
dilatation cardiomyopathy.
Transposition of great arteries was found prenatally in 2,9% (3/105) cases.
33,3% (1/3) were diagnosed up to the 22nd gestation week. 66,7% (2/3) operated on in the first days of life. Early neonatal death (1), post operative
exitus letalis (1). Good late post operative result in 1 case: twin pregnancy in a
44 years old mother, in the 27th gestation week one of the twins was found
TGA. In this case the caryotype (normal result) was defined prior to 16th
gestation week. The neonate had successful "switch" procedure in first day of
life.
Coarction of aorta 1% (1/105) increased spectral Doppler in a fetus in 32nd
gestation week of a mother with diabetes mellitus. In all examinations the
abnormal Doppler measurements in the descending aorta were prevailing,
which normalized after birth and no specific treatment was needed.
Anomalous coronary arteries - suspicion to a left coronary artery fistula in a
fetus in 37th gestation week persisted in I % (1/105) cases. After birth no specific
treatment was applied.
Pulmonary artery valve stenosis - 1% (1/105) cases. In the family history of
a 21 years old mother in 32nd gestation week - rubella infection in the first
trimester. The baby after birth is still under paediatric cardiologists' observation.
Truncus arteriosus coiminis (TAC)
was diagnosed in this study in 3.8% cases (4/105) of structural heart
pathologies. This heart disease can be diagnosed also in four-chamber view.
Only in one case from these four truncus arteriousus communis prenatally
diagnosed heart diseases it was diagnosed by 22nd gestation week. Pregnancy
was continued; it ended with a pre-term labour and exitus letalis.
Table 12. It demonstrates TAC correlation with maternal and family risk
factors, caryotype and outcome.
Diagnosis Family/maternal risk factors Caryotype
Outcome
(number)
TAC (2)
_
_
EL
TAC
Maternal exposure to alcohol
-OP* /PCo
TAC
CHD previus child
22ql 1 deletion ** PCo
Abbreviations: EL- exitus letalis after birth, OP - operated, PCo - under
paediatric cardiologist's observation;
*after birth there is pulmonary artresia with a ventricular septal defect, operated
at neonatal age;
**22 q 11 chromosome deletion is found in mother and two babies, both with a
congenital heart disease - conotruncal anomaly.
In conclusion: termination of pregnancy occurred in 18,7% (42/225) cases,
exitus letalis - 4,4% (10/225) at an early neonatal period, fetus mortus 0,4%
(1 /225), heart operations in a neonatal period 1,8% (4/225), normal fetus heart
after birth has been found in 22,2% (50/225) which make up a group of heart
rhythm disorders, and about 53 % (118/225) remain paediatric cardiologist
care. The number of structural heart diseases diagnosed in a four-chamber
view was greatly prevalent (89,5%, 94/105) over those, which were diagnosed
by examining great arteries (10,5%, 11/105).
Within five years while doing 2445 fetal echocardiogramms, false negative
results were found in 0,2% (4/2445) cases, from them - subaortal ventricular
septal defects (2), later they were successfully operated, and valvular pulmonary
artery stenosis (2), which was manifested only after birth, while doing a fetus
echocardiogramm not seen in 19 gestation weeks, which was retrospectivelly
proved also by a video-recorded examination. No severe or combined heart
pathologies are included in this group. There are no data on false positive
results.
DISCUSSION OF RESULTS
Prenatal diagnostics of congenital heart diseases occupies a significant role in
children cardiology [Allan L.D. et al., 2002; Buskens E. et al., 1996; Hsien C.
etal., 1996; Gembruch U., 1997; Meberg A.,2002, Sharland G.K.et al.,
1992]. Taking into account a high mortality rate from congenital pathologies
not only in the whole world, Latvia including [Zīdere V., et al., 2003], timely
diagnostics of congenital heart diseases pathologies ensures a provision of
professional and qualitative care at an early neonatal period, as well as
reduces infant mortality [Hafner E. et al., 1998]. Early diagnostics of pathologies
gives a chance to the family decide whether to continue pregnancy or to
interrupt it, if the existing heart pathology is fatal or its treatment
possibilities are limited and prognosis for a good life quality is doubtful
[Allan L.D., 2000; Menahem S. et al., 2003]. Considering the high neonatal
and infant mortality (9.9%0, 2002) in Latvia, including congenital anomalies
(3,0%0,2002) and congenital heart pathologies (0,9%0,2002) (Year-Book of
Health Care Statistics in Latvia, 2002, p.35-37), proper and timely medical care
improves the quality of medical care and the demographic situation in the
country.
AEPC fetal working group recommendations says that in order to diagnose
and make the diagnosis precise, its perinatal diagnosis, fetus echocardiography
has to be done by a paediatric cardiologist, preferably at a children cardiology
centre. In the countries where prenatal cardiology centres are not established,
fetal heart examination is done by gynaecologists and even midwives [Berghella
V. et al., 2001; Eurenius K. et al., 1999; Skansky M. et al., 2000], but such a
system is not considered as optimal. Taking into consideration Latvia's
geographical situation, its comparatively small territory and the population
rate, there is an opportunity for the first time to develop an ideal AEPC
recommended model in Latvia.
Leading world specialists in fetal cardiology keep discussing about a series of
indications for fetus echocardiography, such as mother's age, diabetes at
pregnancy, echogenic cardiac focus, alcoholism [Allan L.D. et al., 2000; Cooper
M.J. et al., 1995; Dildy G.A. et al., 1996; Huggon I.C. et al., 2001; Jeanty P.,
1996], However, organizing medical care in Latvia in this field for the first
time and analyzing the situation in total, we can draw conclusions that, taking
into account the fact that paediatric cardiology and especially fetal cardiology
is a very new medical branch, comparing it to the Western countries, and
gynaecologists and obstetricians having a comparatively short experience, it
would be worth to take into account also relative indications of fetal heart
disease in order to improve mother and child health care system in Latvia.
Comparing the situation with the first year experience in prenatal cardiology,
the total number of fetal echocardiogramms has considerably increased from
135 in the first year (1998) to 765 in thefifthyear (2002). Consequently, the
number of diagnosed pathologies has increased as well, from 4 (1998) to 44
(2002).
The data mentioned characterize not only paediatric cardiologists' work in
fetal cardiology but also a successful work done by gynaecologists-obstetricians
and geneticians in this field, which, in its turn, indisputably improves health
care in Latvia. Comparing it with results of experienced specialists, and
analysing our 2445 fetal echocardiogramms, 225 (9,2%) examinations are of
pathological findings, these data can be considered satisfactory or even good,
comparing them in absolute numbers, e.g., M. Eronen study (1997) at the
Children's hospital, University of Helsinki - twelve years' experience - 422
echocardiogramms with 193 (46%) pathological findings (Table 14).
Undoubtedly a much greater experience is in the countries of longstanding
traditions in fetal cardiology, for example, Guy's hospital in London [LD Allan
et al.,2000; Buskens E. Et al., 1996]. Other factors are also of importance, such
as, population rate, pregnancy rate, financial resources allocated for the
development of this field- Comparing the study data of the Latvian State
Children Cardiology Centre with those of other countries, 46,7% of pathological
examinations consist of structural heart pathologies, 27,6% - non-structural
heart pathologies, 25,8% - heart rhythm disorders. The data of comparative
studies by D.H. Brick and L.D. Allan (2000) (Table 13) give the evidence that
the number of prenatally diagnosed heart diseases increases if the number of
fetal echocardiograms increases in those cases when extracardiac pathologies
get diagnosed in routine obstetric ultrasonographies. In the publication
mentioned, there are compared study results from Italy, London (1980-1992),
the United Kingdom, New York (1993-1999) and Yale, the USA. In the New
York study by D.H. Brick, the gestation time from 15-42 week (on average
26), similarly to the data of Italy, London and also Latvia. It is worth mentioning,
that 43% heart pathologies in Italy and Yale, but 68% in London study, were
diagnosed by 24th gestation week. By the way, in a lot of countries this time is
24 gestation weeks - the time for legal pregnancy interruption according to
medical indications and the time when diagnosis of heart pathologies is
considered to be timely (in Latvia - 22 gestation weeks). High data of London
study can be explained by the fact that in the UK there is a very well organized
fetal routine ultrasonographic examination in between 18 to 20 gestation week
in the whole country, just opposite to the USA where this medical service is
not organized in a system and is administered only in case of diagnosing a
heart disease. In Latvia in 31,2% cases the heart pathology was found by 22nd
gestation week including. In Yale study 32% extracardiac, 28% chromosomal
anomalies were diagnosed, while in New York study - 16% extracardiac and
9% chromosomal pathologies were diagnosed. London and Italian study 17% chromosomal pathologies, from them 17% cases showed extracardiac
anomalies. In our study chromosomal pathology during pregnancy was
diagnosed in 8% (19/225) cases, from them 14% - extracardiac anomalies,
postnatally in 4 other cases a genetic syndrome was diagnosed, in total - 10,3%.
Extracardiac pathology 25,3% (57/225) and positive family and mother's history
in 7,6% cases.
Table 13. Characteristics of comparative study.
London New York
Yale
Italy
Latvia
1980-1992
1993-1999
ND
16%
32%
17%
25,3%
17%
9%
28%
17,5%
10,3%
24 gest.week
68%
46%
ND
43%
31,2%*
Termination of pregnancy
55%
24%
45%
29%
18,7%
26
26
-26
-26
28
Extracard iacanomalies
Chromosomal anomalies
1998-2003IV
Diagnosis prior to
First diagnoses at
average gest.week
ND-no data; * in Latvia study up to 22 gestation week
Analyzing study data and the experience of clinics in different countries [Allan
L.D., 2000; Brick H.D. et al, 2002; Gill H.K. et al., 2003], including the
previously mentioned as well, pregnancies were terminated from 24% to 55%
and even 60% cases. This undeoubtedly correlates to the gestation time at
which the heart pathology has been diagnosed. Studies show that the earlier an
anomaly gets diagnosed, the greater is the rate of interrupted pregnancies. In
the Latvian study 18,7% pregnancies were interrupted where fetal heart
pathologies were diagnosed. It can be explained by the fact that the time limit
for legal pregnancy termination is precocious (22 gestation weeks) to the
compared studies (24 gestation weeks), and also slightly lower is the number
of early diagnosed pathologies.
The tendency for pregnancy termination remains despite the rapid development
of pediatric cardiology and cardiosurgery in the last ten years, which might be
due to insufficient retrospective data and experience of management of severe
heart diseases because in many congenital heart diseases the treatment methods
used are comparatively new and there are no studies of further results, as well
as in severe, combined heart pathology cases. Despite possibilities for surgical
correction, parents are still not sure of a chance to provide their expected child
a good life quality [Allan L.D., 2000].
By analyzing the incidence of diagnosed pathologies in detail, the majority of
studies were found to be alike. Among the prenatally diagnosed structural heart
diseases in a four-chamber view [Brick H.D.et al., 2002; Eronen M., 1997; Gill
H.K.et al., 2003; Levi S.,1998; Paladini D.et al., 2002; Skansky M. et al,
2000] most commonly are AVSD, HLHS, tetralogy of Fallot, VSD, followed
by mitral valve atresia, TGA, DORV and others. The study of State Children's
Cardiology Centre is slightly different, the first to be mentioned are VSD,
muscular VSD, HLHS, tetralogy of Fallot, complex heart disease and others.
Studies unequivocally prove that a complete heart examination in routine fetus
investigation may yield maximum results and by adding great arteries views to
traditionaliy used four chamber position, the diagnostics of combined, severe
heart diagnosis increases from 60% to 90% [Allan L.D., 2000; Carvalho J.S.et
al.,2002; Wong S.F.et al., 2003; Hess D.B.et al., 1998; Levi S.et al.,1998].
Table 14. demonstrates our study results in comparison to that of M. Eronen
(1997) at the Children's hospital, University of Helsinki.
* only in a structural pathology group
** termination of pregnancy, fetus mortus, early neonatal death
CONCLUSIONS
1. Fetal heart pathology is a common fetal anomaly in Latvia which can be
diagnosed during pregnancy.
2. By increase of total fetal echocardiogram rate, there is an increase of
diagnosed pathologies from 3% in the first year when starting prenatal
cardiology till 8,6% in the fifth.
3. Paediatric cardiologist with an extra training in prenatal cardiology, by using
now available medical equipment, provides the verification of an early heart
pathology in Latvia starting with the 15th gestation week.
4. Using up-to-date echocardiographic equipment, the Latvian State Children
Cardiology Centre is able to diagnose wide spectre congenital heart anomalies.
5. Fetal heart pathology in Latvia is very often combined with extracardiac
(25,3%) and genetic pathology (10,3%), as well as the risk for a genetic
pathology and a heart disease in a fetus increases in mothers over 35 years 23,3% (p=0,026).
6. The study proves that severe, combined heart pathologies are diagnosed
comparatively late and the medial gestation time at which the heart pathologies
in a fetus are diagnosed for the first time is later in time (28 gestation week) as
compared to the studies in clinics with longstanding experience (26 gestation
week).
7. In our study a fetal heart pathology was diagnosed in 31 % up to 22nd gestation
week which is the legal time for interrupting of pregnancy in Latvia.
8. Timely diagnostics of fetal heart malformations in severe cases of poor life
prognosis allows the family to choose whether to continue pregnancy or
terminate it. In our study - if severe heart diseases are diagnosed timely, the
family decides not to continue pregnancy.
9. Comparing results of our first study in Latvia with those of developed
countries in Europe and the USA which have long-term experience with
diagnosed heart pathologies, no statistically confident differences have been
found.
10. Doing a research within one country, there were worked out
recommendations for fetal heart ultrasonographic examination adapted for
Latvia. Working out and implementing the recommendations for fetal heart
ultrasonographic examination in a doctor's practice, considering the perinatal
care situation in Latvia, as well as teaching gynaecologists and obstetricians in
this field, the results in prenatal and postnatal children cardiology have greatly
improved.
PRACTICAL RECOMMENDATIONS
1. Organizing perinatal care, it is important to envisage the time and to provide
the technical opportunities in order in each fetal ultrasonographic examination
the gynaecologist could pay a special attention to fetal heart examination, great
arteries vessels including.
2. To improve the diagnostic level of fetal heart pathologies, it is important to
examine at least one fetal ultrasonographic examination in the period from 1820th gestation week, but in a high risk pregnancy case starting already from
15-16 gestation week.
3. When examining a fetal heart in routine obstetric ultrasonography, one should
choose an adequate programme (fetal heart) and 5 or 3 MHz transducer,
majority of which are offered by contemporary equipment.
4. By diagnosing a cardiac or any other extracardiac fetal pathology, it is
necessary to have a paediatric cardiologist's consultation.
5.Taking into account a rather small territory of Latvia and its unfavourable
demographic situation - low birth rate and high perinatal mortality, and in
order to preserve a high fetal echocardiographic quality and to ensure an
adequate medical help, in case of a congenital heart risk, the fetal heart
specialized examination has to be done at children cardiology centres.
6. In case of heart pathology, if pregnancy time permits, it is worth doing a
caryotype analysis which would certainly help prognose both prenatal and
postnatal outcome.
7. Diagnostics of prenatal heart pathologies, including heart and genetic ones,
helps the family and doctors choose the further treatment tactics and organize
it correctly, at the same time the medical institutions can plan for medical
resources timely and purposefully.
8. A fetus with a congenital heart pathology can be delivered in a medical
institution which has a close collaboration with a children cardiology centre to
optimize an instant help in each diagnostic category.
9.The information on a possible fetal heart specific examination and
echocardiography has to be available to each family in order to have a possibility
to choose it, even if there are no specific indications or heart pathology risk.
This is a significant psychological aspect during pregnancy - confidence in
having a healthy child.
10. In perspective, striving for an ideal mother and child health care in Latvia,
it would be necessary to provide fetal echochardiography in each pregnancy
and done by a paediatric cardiologist trained in fetal cardiology.