July/August 2008 Newborn Screening Articles
Clin Chim Acta. 2008 Aug;394(1-2):63-6. Epub 2008 Apr 10.
An enzyme immunoassay for determining 17alpha-hydroxyprogesterone in
dried blood spots on filter paper using an ultramicroanalytical system.
González EC, Marrero N, Pérez PL, Frómeta A, Zulueta O, Herrera D, Martínez
L, Castells E.
Department of Neonatal Screening, Immunoassay Center, 134 Street and 25
Avenue, Postal Code 6653, Cubanacán, Playa, Havana, Cuba.
BACKGROUND: 17alpha-hydroxyprogesterone has been used for the diagnosis
of congenital adrenal hyperplasia (CAH) in the newborn period. METHODS: A
simple and rapid competitive ultramicro ELISA assay based on competition
between 17-OHP-alkaline phosphatase conjugate and 17-OHP in blood specimens
for a limited number of binding sites on specific polyclonal rabbit anti-17-OHP
antibodies, has been developed for the measurement of 17-OHP in dried blood
spots on filter paper. The assay buffer contains danazol to displace 17-OHP from
steroid-binding proteins. RESULTS: The 17-OHP assay was completed in 3 h,
with a measuring range of 10-250 nmol/l. The intra- and inter-assay CV were 5.58.2% and 6.4-9.1%, respectively, depending on the 17-OHP concentrations. The
recovery ranged from 98-103%. Of 3750 newborn samples collected on filter
paper, 903 from the national neonatal screening program were analyzed, and the
mean 17-OHP concentration was 12.2 nmol/l. Our assay showed high Pearson
and concordance correlations with the commercially available ICN Neoscreen
ELISA 17alpha-hydroxyprogesterone kit. CONCLUSIONS: The analytical
performance characteristics of our 17-OHP Neonatal UMELISA suggest that it
can be used for the neonatal screening of CAH.
Eur J Hum Genet. 2008 Aug;16(8):875-9. Epub 2008 Feb 27.
p.[G576S; E689K]: pathogenic combination or polymorphism in Pompe
disease?
Kroos MA, Mullaart RA, Van Vliet L, Pomponio RJ, Amartino H, Kolodny EH,
Pastores GM, Wevers RA, Van der Ploeg AT, Halley DJ, Reuser AJ.
1Departments of Clinical Genetics and Pediatrics, Erasmus MC, Rotterdam, The
Netherlands.
We discuss four cases of acid alpha-glucosidase deficiency (EC, 3.2.1.3/20)
without evident symptoms of Pompe disease (OMIM No 232300) in individuals
of Asian descent. In three cases, the deficiency was associated with homozygosity
for the sequence variant c.[1726G>A; 2065G>A] in the acid alpha-glucosidase
gene (GAA) translating into p.[G576S; E689K]. One of these cases was a patient
with profound muscular atrophy, another had cardio-myopathy and the third had
no symptoms. The fourth case, the mother of a child with Pompe disease, was
compound heterozygote for the GAA sequence variants c.[1726G>A;
2065G>A]/c.2338G>A (p.W746X) and had no symptoms either. Further
investigations revealed that c.[1726A; 2065A] is a common GAA allele in the
Japanese and Chinese populations. Our limited study predicts that approximately
4% of individuals in these populations are homozygote c.[1726A; 2065A]. The
height of this figure in contrast to the rarity of Pompe disease in Asian
populations and the clinical history of the cases described in this paper virtually
exclude that homozygosity for c.[1726A; 2065A] causes Pompe disease. As
c.[1726A; 2065A] homozygotes have been observed with similarly low acid
alpha-glucosidase activity as some patients with Pompe disease, we caution they
may present as false positives in newborn screening programs especially in Asian
populations.European Journal of Human Genetics (2008) 16, 875-879;
doi:10.1038/ejhg.2008.34; published online 27 February 2008.
Int J Pediatr Otorhinolaryngol. 2008 Aug;72(8):1281-5. Epub 2008 Jun 20.
Cochlear microphonics in sensorineural hearing loss: Lesson from newborn
hearing screening.
Ahmmed A, Brockbank C, Adshead J.
Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom.
The diagnostic dilemma surrounding the presence of cochlear microphonics (CM)
coupled with significantly elevated auditory brainstem response (ABR) thresholds
in babies failing the newborn hearing screening is highlighted. A case report is
presented where initial electo-diagnostic assessment could not help in
differentiating between Auditory Neuropathy/Auditory Dys-synchrony (AN/AD)
and sensorineural hearing loss (SNHL). In line with the protocol and guidelines
provided by the national Newborn Hearing Screening Programme in the UK
(NHSP) AN/AD was suspected in a baby due to the presence of CM at 85dBnHL
along with click evoked ABR thresholds of 95dBnHL in one ear and 100dBnHL
in the other ear. Significantly elevated thresholds for 0.5 and 1kHz tone pip ABR
fulfilled the audiological diagnostic criteria for AN/AD. However, the possibility
of a SNHL could not be ruled out as the 85dBnHL stimuli presented through
inserts for the CM would have been significantly enhanced in the ear canals of the
young baby to exceed the threshold level of the ABR that was carried out using
headphones. SNHL was eventually diagnosed through clinical and family history,
physical examination and imaging that showed enlarged vestibular aqueducts.
Presence of CM in the presence of very high click ABR thresholds only suggests
a pattern of test results and in such cases measuring thresholds for 0.5 and 1kHz
tone pip ABR may not be adequate to differentiate between SNHL and other
conditions associated with AN/AD. There is a need for reviewing the existing
AN/AD protocol from NHSP in the UK and new research to establish parameters
for CM to assist in the differential diagnosis. A holistic audiological and medical
approach is essential to manage babies who fail the newborn hearing screening.
Int J Pediatr Otorhinolaryngol. 2008 Aug;72(8):1193-201. Epub 2008 Jun 12.
Comparison of two-step transient evoked otoacoustic emissions (TEOAE)
and automated auditory brainstem response (AABR) for universal newborn
hearing screening programs.
Benito-Orejas JI, Ramírez B, Morais D, Almaraz A, Fernández-Calvo JL.
ENT Department, Hospital Clínico Universitario, Valladolid, Spain.
OBJECTIVE: Both transitory auditory otoemissions (TEOAE) and automated
auditory brainstem responses (AABR) are considered adequate methods for
universal hearing screening. The goal of this study was to compare the results
obtained with each device, applying the same screening procedure. MATERIALS
AND METHODS: From 2001 to 2003, all the newborns in our health area (2454
infants) were evaluated with TEOAE (ILO92, otodynamics) and all those born
from 2004 to 2006 (3117) were evaluated with AABR (AccuScreen, FischerZoth). The population studied included all well newborns and those admitted to
neonatal intensive care units (NICU). The first screening was normally
undertaken with well babies during the first 48h of life, before hospital discharge.
Infants referred from this first step underwent a second screening after hospital
discharge, before they were a month old. RESULTS: The results from each study
group were compared and analyzed for significant differences. TEOAE screening
yielded 10.2% fail results from the first screening step; AABR gave 2.6%. In the
second screening step, 2% of the newborns screened with TEOAE were referred,
whereas 0.32% of those screened with AABR were referred. These differences
are statistically significant. CONCLUSIONS: Although AABR screening tests
involve a slightly higher cost in time and money than TEOAE, the results
obtained compensate this difference. AABR gives fewer false positives and a
lower referral rate; the percent of infants lost during follow-up is consequently
smaller. Therefore, in our environment, universal newborn auditory screening
with AABR is more effective than that with TEOAE.
J Pediatr. 2008 Aug;153(2):A3.
The French cystic fibrosis newborn screening program.
Wilmott RW.
J Pediatr. 2008 Aug;153(2):228-33, 233.e1. Epub 2008 Apr 18
Implementation of the French nationwide cystic fibrosis newborn screening
program.
Munck A, Dhondt JL, Sahler C, Roussey M.
CF center, University hospital Robert Debré, AP-HP, Paris, France.
anne.munck@rdb.aphp.fr
OBJECTIVES: To describe optimization of a nationwide newborn screening
program for cystic fibrosis (CF) that combines an immunoreactive trypsinogen
(IRT) assay and DNA mutation analysis in dried blood samples at day 3. STUDY
DESIGN: Data from regional screening laboratories and CF care centers were
centralized and periodically analyzed to allow adaptation, thus limiting the
number of false-positive cases. RESULTS: A total of 2717905 infants were
screened between 2002 and 2005. Flow chart protocol was modified twice. First,
the IRT d3 cutoff value increased from 60 to 65 microg/L, thus decreasing the
percentage of samples requiring mutation analysis from 0.82% to 0.64%. Second,
for infants with no mutations using the screening panel, a recall for IRT was
performed only if IRT d3 was > 100 microg/L; the percentage of recalls decreased
from 0.51% to 0.12%, and the percentage of infants requiring a sweat test
decreased from 0.14% to 0.01%. No significant change in the CF detection rate
was observed after these 2 modifications. A total of 625 CF cases were detected,
and 22 false-negative findings (3.4%) were observed, most of them inevitable,
with a low initial IRT. CONCLUSIONS: The centralized data analysis led to
changes in the screening strategy to optimise the newborn screening program.
Pediatric Health 2008;2(4):411-429.
What’s new in newborn screening.
Therrell BL, Buechner C, Lloyd-Puryear MA, van Dyck PC, Mann MY.
Eur J Pediatr. 2008 Jul 31. [Epub ahead of print]
Neonatal screening for congenital hypothyroidism in the Federation of
Bosnia and Herzegovina: eight years' experience.
Tahirović H, Toromanović A.
Department of Pediatrics, University Clinical Center, Trnovac bb, 75000, Tuzla,
Bosnia and Herzegovina, husref.tahirovic@untz.ba.
This report demonstrates the prevalence of primary congenital hypothyroidism
(CH) in the Federation of Bosnia and Herzegovina and summarizes the laboratory
data. Neonatal thyroid-stimulating hormone (TSH) was measured in whole blood
drawn between the 3rd and 5th days of life and spotted on filter paper using the
fluorometric assay. Among the 87,061 neonates, 22 had CH, 13 dysgenetic forms,
and nine with thyroids in situ. No differences were found between the two types
in terms of TSH and total T4 concentrations. However, thyroglobulin was
significantly lower in patients with dysgenetic thyroid tissue (p = 0.0023). We
conclude that the prevalence of CH in the Federation of Bosnia and Herzegovina
is 1:3,957 newborns.
Pediatr Res. 2008 Jul 30. [Epub ahead of print]
Development of a new enzymatic diagnosis method for very-long-chain acylCoA dehydrogenase deficiency by detecting 2-hexadecenoyl-CoA production
and its application in tandem mass spectrometry-based selective screening
and newborn screening in Japan.
Tajima G, Sakura N, Shirao K, Okada S, Tsumura M, Nishimura Y, Ono H,
Hasegawa Y, Hata I, Naito E, Yamaguchi S, Shigematsu Y, Kobayashi M.
Department of Pediatrics [G.T., N.S., K.S., S.O., M.T., M.K.], Hiroshima
University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan;
Department of Pediatrics [Y.N.], National Hospital Organization Kure Medical
Center, Kure 737-0023, Japan; Department of Pediatrics [H.O.], Hiroshima
Prefectural Hospital, Hiroshima 734-8530, Japan; Department of Pediatrics [Y.H.,
S.Y.], Shimane University, Izumo 693-8501, Japan; Department of Pediatrics
[I.H.], Department of Health Science [Y.S.], University of Fukui, Fukui 9101193, Japan; Department of Pediatrics [E.N.], University of Tokushima,
Tokushima 770-8503, Japan.
The introduction of tandem mass spectrometry (MS/MS) has made it possible to
screen for very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. To
confirm the diagnosis in cases with an abnormal profile of blood acylcarnitines,
we developed a new enzymatic assay method for determining dehydrogenase
activity toward palmitoyl-CoA (C16:0) in lymphocytes. Using this method, the
production of 2-hexadecenoyl-CoA (C16:1) by crude cell lysates can be directly
quantified using high-performance liquid chromatography. We applied the assay
to 7 myopathic patients, 7 hypoglycemic patients, and 2 presymptomatic
newborns with elevated levels of tetradecenoylcarnitine (C14:1 AC) in blood, and
found impaired VLCAD activity in all of the 7 myopathic patients and both of the
2 newborns. All of the 7 hypoglycemic patients had normal level of the enzyme
activity. Results of the ACADVL gene analysis were in consistent with the
enzymatic diagnosis. These results suggest that MS/MS-based screening for
VLCAD deficiency using blood C14:1 AC as the indicator may show a
considerably high false-positive rate in selective screening of symptomatic
patients. Our practical enzymatic assay can be a useful test for the accurate
diagnosis of VLCAD deficiency cases screened by MS/MS.
Eur J Pediatr. 2008 Jul 24. [Epub ahead of print]
Determination of EDTA in dried blood samples by tandem mass
spectrometry avoids serious errors in newborn screening.
Fingerhut R, Dame T, Olgemöller B.
Laboratory Becker, Olgemöller & Colleagues, Führichstr. 70, 81671, Munich,
Germany, r.fingerhut@labor-bo.de.
Newborn screening programs use whole blood dried on filter paper as the
standard specimen. Metabolites are reasonably stable and can easily be sent to
screening laboratories by regular mail. The recommended sample collection
procedure is to spot native blood without anticoagulants onto the filter paper,
because anticoagulants can interfere with the different laboratory methods.
However, visual examination of the blood spots cannot always detect
contamination. In this study, whole blood was drawn by venous puncture from a
healthy volunteer, spiked with the corresponding metabolites and EDTA, and
spotted onto filter paper. TSH and 17alpha-hydroxyprogesterone were determined
by time resolved fluoroimmunoassays with the AutoDelfia system. Total
galactose, biotinidase activity, and galactose-1-phosphate uridyltransferase
activity were measured photometrically or fluorometrically. Succinyl acetone was
estimated indirectly through the inhibition of porphobilinogen synthase activity
(PBGS assay). EDTA, amino acids, and acylcarnitines were converted to the
corresponding butyl esters, after extraction with methanol, and analysed by LCMS/MS. EDTA contamination gives falsely elevated 17-OHP values and falsely
reduced TSH and PBGS values. The inclusion of an EDTA determination in
routine screening revealed that at least 0.06% of newborn screening samples were
contaminated with EDTA. In conclusion, non-conformity during the preanalytical phase is a source of false positive and false negative screening results.
Determination of EDTA from NBS blood spots can reliably identify these
samples and prevent screening errors.
Biomed Chromatogr. 2008 Jul 23. [Epub ahead of print]
Improved method to determine succinylacetone in dried blood spots for
diagnosis of tyrosinemia type 1 using UPLC-MS/MS.
Al-Dirbashi OY, Rashed MS, Jacob M, Al-Ahaideb LY, Al-Amoudi M, Rahbeeni
Z, Al-Sayed MM, Al-Hassnan Z, Al-Owain M, Al-Zeidan H.
National Laboratory for Newborn Screening, Department of Genetics, King Faisal
Specialist Hospital and Research Centre, PO Box 3354 Riyadh 11211 Saudi
Arabia.
We describe an improved diagnostic method for tyrosinemia type 1 based on
quantifying succinylacetone in dried blood spots by ultra-performance liquid
chromatography tandem mass spectrometry. Succinylacetone extracted from a
single 3/16 inch disk of specimen collection paper containing a dried blood spot
was derivatized with dansylhydrazine, separated on an Acquity UPLC BEH C(18)
column (2.1 x 50 mm, 1.7 microm) and detected by electrospray ionization
tandem mass spectrometry. Succinylacetone derivative eluted at 0.6 min with a
complete run time of 1 min. Using a (13)C(4) labeled succinylacetone as an
internal standard, the calibration plot was linear up to 100 micromol/L with a
detection limit (S/N = 3) of 0.2 micromol/L. Intra-day (n = 13) and inter-day (n =
10) variations were better than 10%. The cutoff level of succinylacetone in dried
blood spots from healthy infants obtained by the current method was 0.63
micromol/L (n = 151). In dried blood spots from patients with established
tyrosinemia type 1 (n = 11), concentration of succinylacetone was 6.4-30.8
micromol/L. Copyright (c) 2008 John Wiley & Sons, Ltd.
J Inherit Metab Dis. 2008 Jul 23. [Epub ahead of print]
Detection of urinary hexanoylglycine in the diagnosis of MCAD deficiency
from newborn screening.
Downing M, Manning NJ, Dalton RN, Krywawych S, Oerton J.
Department of Clinical Chemistry, The Children's Hospital, Sheffield, S10 2TH,
UK, Melanie.downing@sch.nhs.uk.
PMID: 18649007 [PubMed - as supplied by publisher]
Soc Sci Med. 2008 Jul 17. [Epub ahead of print
Is my sick child healthy? Is my healthy child sick?: Changing parental
experiences of cystic fibrosis in the age of expanded newborn screening.
Grob R.
Sarah Lawrence College, Bronxville, NY, United States.
This paper explores how rapid growth in the USA of mandatory newborn
screening (NBS) leading to a diagnosis of cystic fibrosis is changing, for affected
families, their experience of illness versus disease. Qualitative research
comparing newborn screening and post-symptomatic diagnostic experiences
suggests a number of potent consequences associated with affixing a disease
diagnosis through newborn screening. The early, unsought diagnosis deeply
affects parents' feeling of competence to care for their newborn and their sense of
who the child is, and places the disease - rather than the process of "falling in love
with" the new baby - at centre stage during the child's early weeks and months;
and causes health professionals to loom very large in the family's life at this
formative time. With newborn genetic screening continuing to expand rapidly in
the USA for a range of other conditions that may not be immediately
symptomatic, we can expect that the newborn period will be significantly altered
in these ways for a growing segment of the population.
Otol Neurotol. 2008 Jul 9. [Epub ahead of print]
Newborn Hearing Screening in Infants With Cleft Palates.
Chen JL, Messner AH, Curtin G.
*Department of Otolaryngology and Communication Enhancement, Children's
Hospital, Boston, Massachusetts; daggerOtolaryngology/Head & Neck Surgery
and Pediatrics, and double daggerLucile Packard Children's Hospital at Stanford,
Palo Alto, California, U.S.A.
OBJECTIVE:: The high incidence of conductive hearing loss from serous
effusion in patients with cleft palate is well known. This study investigates the
results and interpretation of newborn hearing screening in infants with cleft
palates. STUDY DESIGN: Retrospective cohort review. PATIENTS:: One
hundred fourteen newborns with cleft palate, with or without cleft lip, born
between 1999 and 2005 and referred to a craniofacial anomalies clinic.
INTERVENTION:: Tympanostomy tubes were placed in 102 newborns, and
follow-up audiograms were available for 104 infants. MAIN OUTCOME
MEASURES:: Hearing screening outcomes were collected. Sex, gestational
period, type of screening performed, the presence of hearing loss after tube
placement, and the presence of associated syndromes were noted. RESULTS::
Eighty-two (72%) of 114 of newborns with cleft palates passed their hearing
screen. Of the 30 newborns who failed their hearing screen, and had
tympanostomy tubes placed, 13 (43%) had persistent hearing loss after tube
placement. Factors predicting persistent hearing loss include cleft palate alone,
female infants, and the presence of an associated syndrome. CONCLUSION::
Newborns with cleft palate are at higher risk of failing their newborn hearing
screen compared with healthy neonates. Detection of sensorineural or conductive
hearing loss unrelated to middle ear effusions is more difficult in this at-risk
population with cleft palate because of the high prevalence of serous otitis media.
Arch Dis Child Fetal Neonatal Ed. 2008 Jul;93(4):F280-5. Epub 2007 Nov 26.
Congenital cytomegalovirus: association between dried blood spot viral load
and hearing loss.
Walter S, Atkinson C, Sharland M, Rice P, Raglan E, Emery VC, Griffiths PD.
St George's Hospital, Blackshaw Road, Tooting, London SW17 0QT, UK.
waltes@gosh.nhs.uk
AIM: To investigate the relation between cytomegalovirus (CMV) viral load on
dried blood spots (DBS) from newborn biochemical screening ("Guthrie") cards,
and sensorineural hearing loss (SNHL) in congenital CMV. DESIGN: Crosssectional study with retrospective case-note review. SETTING: Seven paediatric
audiology departments in the United Kingdom. PATIENTS: 84 children, median
age 7 years: 43 with known congenital CMV, 41 with unexplained SNHL.
INTERVENTIONS: Half a DBS was tested for CMV DNA viral load by
quantitative real-time polymerase chain reaction (PCR). MAIN OUTCOME
MEASURES: Pure tone average hearing thresholds (0.5-4 kHz). RESULTS: DBS
CMV DNA viral load significantly correlated with hearing thresholds for the
worse and better hearing ears (Spearman's rank correlations: r = 0.445, p = 0.008
and r = 0.481, p = 0.004 respectively). Multivariable logistic regression showed
that the effect of DBS viral load on the risk of SNHL remained important, when
age and central nervous system involvement had been taken into account (odds
ratio (OR) 2.76, 95% confidence interval (CI) 1.14 to 6.63, p = 0.024). The mean
log DBS viral load was significantly higher in children with SNHL than in those
with normal hearing (2.69 versus 1.64, 95% CI -1.84 to -0.27, p = 0.01). 8/35
(23%) children with unexplained SNHL tested positive for CMV DNA on DBS.
One false positive result was obtained. CONCLUSION: The risk of SNHL
increased with DBS viral load. Further studies should investigate whether DBS
CMV testing has a role in identifying asymptomatic congenitally infected
neonates at risk of SNHL, and whether antiviral treatment can reduce this risk.
Int J Pediatr Otorhinolaryngol. 2008 Jul;72(7):991-1001. Epub 2008 Apr 22.
Hospital-based universal newborn hearing screening for early detection of
permanent congenital hearing loss in Lagos, Nigeria.
Olusanya BO, Wirz SL, Luxon LM.
Institute of Child Health and Great Ormond Street Hospital for Children NHS
Trust, University College London, 30 Guilford Street, London WC1N 1EH, UK;
Institute of Child Health and Primary Care, College of Medicine, University of
Lagos, Surulere, Nigeria.
OBJECTIVE: To determine the feasibility and effectiveness of hospital-based
universal newborn hearing screening programme for the early detection of
permanent congenital or early-onset hearing loss (PCEHL) in Lagos, Nigeria.
METHODS: A cross-sectional pilot study based on a two-stage universal
newborn hearing screening by non-specialist health workers using transient
evoked otoacoustic emissions (TEOAE) and automated auditory brainstemresponse (AABR) in an inner-city maternity hospital over a consecutive period of
40 weeks. The main outcome measures were the practicality of screening by nonspecialist staff with minimal training, functionality of screening instruments in an
inner-city environment, screening coverage, referral rate, return rate for diagnosis,
yield of PCEHL and average age of PCEHL confirmation. RESULTS: Universal
hearing screening of newborns by non-specialist staff without prior audiological
experience is feasible in an inner-city environment in Lagos after a training period
of two-weeks. Notwithstanding excessive ambient noise within and outside the
wards, it was possible to identify a test site for TEOAE screening within the
hospital. The screening coverage was 98.7% (1330/1347) of all eligible newborns
and the mean age of screening was 2.6 days. Forty-four babies out of the 1274
who completed the two-stage screening were referred yielding a referral rate of
3.5%. Only 16% (7/44) of babies scheduled for diagnostic evaluation returned and
all were confirmed with hearing loss resulting in an incidence of 5.5 (7/1274) per
1000 live births or a programme yield of 5.3 (7/1330) per 1000. Six infants had
bilateral hearing loss and the degree was severe (>/=70dBnHL) in three infants,
moderate (40dBnHL) in one infant and mild (<40dBnHL) in two infants. The age
at diagnosis ranged from 46 days to 360 days and only two infants were
diagnosed within 90 days. CONCLUSIONS: Hospital-based universal hearing
screening of newborns before discharge is feasible in Nigeria. Non-specialist staff
are valuable in achieving a satisfactory referral rate with a two-stage screening
protocol. However, a more efficient tracking and follow-up system is needed to
improve the return rate for diagnosis and age of confirmation of hearing loss.
J Clin Endocrinol Metab. 2008 Jul;93(7):2654-61. Epub 2008 May 6.
Quality of life, developmental milestones, and self-esteem of young adults
with congenital hypothyroidism diagnosed by neonatal screening.
van der Sluijs Veer L, Kempers MJ, Last BF, Vulsma T, Grootenhuis MA.
Pediatric Psychosocial Department, Emma Children's Hospital Academic Medical
Center, G8-224, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
L.vandersluijsveer@amc.uva.nl.
Context: With advances in the treatment of congenital hypothyroidism (CH), the
neuropsychological functioning of CH patients is considerably improved.
Although much is written about cognitive and motor development, little is known
about emotional and social consequences for patients growing up with CH,
diagnosed by neonatal screening. Objectives: The objectives of the study were to:
1) compare health-related quality of life (HRQoL), developmental milestones also
called course of life (CoL), sociodemographical outcomes, and self-esteem of CH
patients with the general population; and 2) explore whether severity of CH was
related to these outcomes. Design/Setting/Patients: A total of 69 young adults
with CH, born in The Netherlands in 1981-1982, completed the "TNO-AZL
Questionnaire for Adult's Health related Quality of Life" questionnaire, the CoL
survey (developmental milestones and sociodemographical outcomes), and a selfesteem questionnaire. Main Outcome Measures: HRQoL, CoL, social
demographical outcomes, and self-esteem in young adults with CH were
determined. Results: CH patients are more often at risk for HRQoL impairment
and reported lower HRQoL on several domains (cognitive functioning, P <
0.0001; sleeping, P < 0.004; pain, P < 0.0001; daily activities, P < 0.004; vitality,
P < 0.0001; aggressiveness, P < 0.0001; and depressive moods, P < 0.0001)
compared with healthy adults. Patients reported a lower self-esteem (P < 0.005)
and had a delayed CoL on the domain of social development (P < 0.016). There
were no significant within-group differences between the severity groups for
HRQoL, CoL, and self-esteem. Conclusions: Negative consequences in terms of
HRQoL, development, and self-esteem are prevalent in young adults with CH.
Health care physicians should be attentive to these consequences and provide
additional support (emotional and educational guidance) if necessary.
Laryngoscope. 2008 Jul;118(7):1253-6
Outcomes and efficacy of newborn hearing screening: strengths and
weaknesses (success or failure?).
Korres S, Nikolopoulos TP, Peraki EE, Tsiakou M, Karakitsou M,
Apostolopoulos N, Economides J, Balatsouras D, Ferekidis E.
1st and 2nd Department of Otorhinolaryngology, Athens University, Athens,
Greece.
OBJECTIVE: To assess the outcomes of neonatal hearing screening with regard
to the final diagnosis in a very large number of newborns and investigate related
strengths and weaknesses of the program. SUBJECTS: In this study, 76,560
newborns were assessed. METHOD: All neonates were assessed using transient
evoked otoacoustic emissions (TEOAEs). RESULTS: From the 76,560 neonates
screened, 1,564 (2%) failed the test. According to the screening protocol, all
parents of failed neonates were asked to bring their children 1 month following
discharge to repeat the test. Of the 541 (34.6%) newborns who repeated the test,
303 (56%) were found normal and 238 (44%) again failed TEOAE. The latter
children were referred to two special public centers for full audiology evaluation.
In addition, 124 neonates were also referred due to other reasons revealed in the
screening process (family history, high levels of bilirubin, etc.). Of the 362
children who were referred to the two special audiology centers, 113 (31.2%)
were evaluated by these two centers. In addition, 42 children who had failed
initial screening and did not show up for a follow-up appointment to repeat
TEOAE were also assessed in the same centers. Of the 155 children who had a
special audiologic evaluation, 56 (36.1%) were found to have hearing loss (HL)
and 99 (63.9%) normal hearing. In detail, 28 had bilateral sensorineural HL
greater than 40 dB, 10 had unilateral sensorineural HL greater than 40 dB, and 18
had otitis media with effusion or other conductive HL. CONCLUSIONS: Derived
from the present study: 1) repeated testing of "failed" newborns in the maternity
hospital and before discharge leads to an acceptable referral rate of 2%; 2) the 1month follow-up of "failed" newborns further limits the false positive results but
leads to high rate of newborns lost to follow-up; 3) a dedicated secretariat system
should be implemented to follow-up each "failed" newborn and remind parents
about their follow-up appointments; and 4) additional measures such as detailed
educational material and parental friendly approach should also be implemented.
Mol Genet Metab. 2008 Jul;94(3):287-91. Epub 2008 Apr 14
Newborn screening for glutaric aciduria type I in Victoria: treatment and
outcome.
Boneh A, Beauchamp M, Humphrey M, Watkins J, Peters H, Yaplito-Lee J.
Metabolic Service, Genetic Health Services Victoria, Royal Children's Hospital,
Melbourne, Victoria 3052, Australia. avihu.boneh@ghsv.org.au
Between October 2001 and September 2007, a total number of 391,651 neonates
were screened in Victoria using Tandem Mass Spectrometry and 6 newborns were
diagnosed as having GA I, giving an incidence of 1:65,275 (CI:
1:29,988=1:177,861). Another patient was diagnosed through cascade screening
of children born before the implementation of the expanded newborn screening
program. Patients were treated by mild protein restriction (2-2.5 g/kg/day) and
carnitine supplementation when well, focussing on the aggressive management of
intercurrent illnesses (temporary cessation of protein intake, increase in calorie
intake, IV carnitine, aggressive anti febrile and anti infectious treatment),
including prophylactic admissions to hospital. Overall, our patients had 35
admissions to hospital, of which 15 were in the first year of life. None had a post
infectious dystonic syndrome. Neuropsychological examinations revealed normal
to high cognitive and gross motor function in all patients but one, with some
deficiencies in fine motor activities and different levels of speech abnormalities in
all patients. Since therapeutic approaches for GA I, although not uniform, are well
established and have been documented to be effective, newborn screening for this
disorder should prove justified. A therapeutic approach of dietary modification,
IV carnitine and aggressive treatment of intercurrent illness seems to prevent the
severe neurological complications of GA I. More in-depth consideration of speech
and language function is necessary to document specific deficits in children with
GA I and plan proactive interventions.
Pediatr Pulmonol. 2008 Jul;43(7):638-41.
Elevated IRT levels in African-American infants: implications for newborn
screening in an ethnically diverse population.
Giusti R; New York State Cystic Fibrosis Newborn Screening Consortium.
Collaborators (10)
Comber P, Germana J, Ting A, Quittell L, Berdella M, Ren C, Kier C, Anbar R,
Boyer J, Caggana M.
Department of Pediatrics, Long Island College Hospital, Brooklyn, New York,
USA. giucfdoc@pol.net
SUMMARY: During the first 4 years of newborn screening (NBS) for Cystic
Fibrosis (CF) in New York there was a statistically significant, twofold greater
relative risk of an Immunoreactive Trypsinogen (IRT) level greater than 95% in
African-American infants. The reason for this previously reported increase in IRT
level in African-American infants is unclear. The positive predictive value of a
screen positive result in this population was only 0.3%. The bulk of screenpositive African-American infants were in the top 0.2% (IRT) group, with no CF
mutations isolated. Repeat IRT testing at 2-3 weeks of age may represent a
suitable approach to decrease the false-positive rate in this population.
Pediatr Pulmonol. 2008 Jul;43(7):648-55
Improved pulmonary and growth outcomes in cystic fibrosis by newborn
screening.
Collins MS, Abbott MA, Wakefield DB, Lapin CD, Drapeau G, Hopfer SM,
Greenstein RM, Cloutier MM.
Department of Pediatrics, Connecticut Children's Medical Center, Hartford,
Connecticut 06106, USA. mcollin@ccmckids.org
BACKGROUND: Newborn screening for cystic fibrosis (CF) is effective in
improving long-term growth outcomes. However, there is conflicting evidence
that early diagnosis maintains normal pulmonary function. Our goal was to
determine if newborn screening results in improved longitudinal growth and
maintenance of normal pulmonary function. METHODS: A retrospective study of
individuals with CF born in Connecticut between 1983 and 1997 was conducted
by medical record and CF Foundation Registry review. Growth, pulmonary
function and bacterial acquisition/colonization data, from diagnosis through July
1, 2005, were compared in those diagnosed by newborn screen (n = 34) to those
diagnosed by sweat test after symptom appearance (n = 21). RESULTS: Screened
individuals demonstrated greater weight and height for age at diagnosis (P = 0.01
and 0.01) and through 15 years of age (P = 0.0002 and 0.01). Body mass index
was higher in screened individuals (21 vs. 18 kg/m(2)) at 15 years of age (P =
0.01). At 15 years of age, screened individuals had a clinically higher forced
expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC; 90% and
104% predicted) than non-screened individuals (74% and 91% predicted; P = 0.08
and 0.10). Over a 9-year period, from ages 6 to 15, percent predicted FEV(1) and
FVC increased by 4% and 13% in screened individuals; and declined by 14% and
5% respectively in non-screened individuals (P = 0.01 and 0.02).
Acquisition/colonization of Pseudomonas aeruginosa was similar between groups
(P = 0.23). CONCLUSIONS: In this CF cohort, individuals diagnosed by
newborn screening have improved growth and preservation of normal pulmonary
function without increased risk of Pseudomonas aeruginosa colonization.
Pediatrics. 2008 Jul;122(1):210-1; author reply 211
Comment on:
Pediatrics. 2006 Aug;118(2):448-56.
A false-positive newborn screening result: goat's milk acidopathy.
Chapman KA, Ganesh J, Ficicioglu C.
PMID: 18596009 [PubMed - indexed for MEDLINE]
Pediatrics. 2008 Jul;122(1):192-7
Adverse medical outcomes of early newborn screening programs for
phenylketonuria.
Brosco JP, Sanders LM, Seider MI, Dunn AC.
Department of Pediatrics, Miller School of Medicine, University of Miami, PO
Box 016820, Miami FL 33101, USA. jbrosco@miami.edu
OBJECTIVE: Despite the success of current newborn screening programs, some
critics have argued that in the 1960s hundreds of children with false-positive
results for phenylketonuria suffered death or disability from treatment with
restrictive diets. Medically adverse outcomes after false-positive results may be a
reason to be cautious when expanding current newborn screening programs. We
sought to determine if newborn screening programs for phenylketonuria before
1980 led to adverse medical outcomes in children with false-positive results.
PATIENTS AND METHODS: We examined the history of newborn screening
programs for phenylketonuria in the United States. We reviewed the historical
scholarship, conducted a systematic search for medical adverse outcomes, and
interviewed key participants in the history of newborn screening programs.
RESULTS: We found no population-based studies of early screening programs
for phenylketonuria. One author reported 2 infants treated with restrictive diets
after false-positive results for phenylketonuria who were developmentally
delayed, and there is unpublished evidence of 4 additional cases of inappropriate
treatment, although adverse outcomes were not documented. There were also 4
published reports of adverse medical outcomes after treating children with
phenylketonuria variants, as screening for phenylketonuria revealed infants with
intermediate or transiently high levels of phenylalanine. CONCLUSIONS: We
found little evidence of death or disability that resulted from the inappropriate
treatment of well children who were falsely identified by early newborn screening
programs. Because the first decade of newborn screening typically reveals
diagnostic and therapeutic complexity, systematic follow-up of screened
populations and rapid dissemination of results may reduce morbidity/mortality
rates.
Pediatrics. 2008 Jul;122(1):143-8
Comment in:
Pediatrics. 2008 Jul;122(1):174-6.
Universal screening for hearing loss in newborns: US Preventive Services
Task Force recommendation statement.
US Preventive Services Task Force.
Collaborators (16)
Calonge N, Petitti DB, DeWitt TG, Gordis L, Gregory KD, Harris R, Isham G,
LeFevre ML, Loveland-Cherry C, Marion LN, Moyer VA, Ockene JK, Sawaya
GF, Siu AL, Teutsch SM, Yawn BP.
US Preventive Services Task Force, Agency for Healthcare Research and Quality,
Rockville, MD 20850, USA. uspstf@ahrq.hhs.gov
DESCRIPTION: This is the 2008 update of the 2001 US Preventive Services
Task Force recommendation on universal newborn hearing screening.
METHODS: The US Preventive Services Task Force weighed the benefits and
harms of universal newborn hearing screening, incorporating new evidence
addressing gaps identified in the 2001 US Preventive Services Task Force
recommendation statement. Published literature on this topic was identified (by
using Medline and Cochrane databases) and systematically reviewed.
RECOMMENDATION: Screen for hearing loss in all newborn infants (B
recommendation).
Pediatrics. 2008 Jul;122(1):e266-76
Universal newborn hearing screening: systematic review to update the 2001
US Preventive Services Task Force Recommendation.
Nelson HD, Bougatsos C, Nygren P; 2001 US Preventive Services Task Force.
Department of Medical Informatics and Clinical Epidemiology, Oregon
Evidence-based Practice Center, Portland, Oregon 97239-3098, USA.
nelsonh@ohsu.edu
OBJECTIVE: This review is an update for the US Preventive Services Task Force
on universal newborn hearing screening to detect moderate-to-severe permanent,
bilateral congenital hearing loss. We focus on 3 key questions: (1) Among infants
identified by universal screening who would not be identified by targeted
screening, does initiating treatment before 6 months of age improve language and
communication outcomes? (2) Compared with targeted screening, does universal
screening increase the chance that treatment will be initiated by 6 months of age
for infants at average risk or for those at high risk? (3) What are the adverse
effects of screening and early treatment? METHODS: Medline and Cochrane
databases were searched to identify articles published since the 2002
recommendation. Data from studies that met inclusion criteria were abstracted,
and studies were rated for quality with predetermined criteria. RESULTS: A
good-quality retrospective study of children with hearing loss indicates that those
who had early versus late confirmation and those who had undergone universal
newborn screening versus none had better receptive language at 8 years of age but
not better expressive language or speech. A good-quality nonrandomized trial of a
large birth cohort indicates that infants identified with hearing loss through
universal newborn screening have earlier referral, diagnosis, and treatment than
those not screened. These findings are corroborated by multiple descriptive
studies of ages of referral, diagnosis, and treatment. Usual parental reactions to an
initial nonpass on a hearing screen include worry, questioning, and distress that
resolve for most parents. Cochlear implants have been associated with higher
risks for bacterial meningitis in young children. CONCLUSIONS: Children with
hearing loss who had universal newborn hearing screening have better language
outcomes at school age than those not screened. Infants identified with hearing
loss through universal screening have significantly earlier referral, diagnosis, and
treatment than those identified in other ways.
Pediatrics. 2008 Jul;122(1):e39-45. Epub 2008 Jun 2
Early detection of Pompe disease by newborn screening is feasible: results
from the Taiwan screening program.
Chien YH, Chiang SC, Zhang XK, Keutzer J, Lee NC, Huang AC, Chen CA, Wu
MH, Huang PH, Tsai FJ, Chen YT, Hwu WL.
Department of Pediatrics, National Taiwan University Hospital, National Taiwan
University School of Medicine, Taipei, Taiwan.
OBJECTIVE: Pompe disease is an autosomal recessive lysosomal storage
disorder that is caused by deficient acid alpha-glucosidase activity and results in
progressive, debilitating, and often life-threatening symptoms involving the
musculoskeletal, respiratory, and cardiac systems. Recently, enzyme replacement
therapy with alglucosidase alpha has become possible, but the best outcomes in
motor function have been achieved when treatment was initiated early. The aim of
this study was to test the feasibility of screening newborns in Taiwan for Pompe
disease by using a fluorometric enzymatic assay to determine acid alphaglucosidase activity in dried blood spots. METHODS: We conducted a large-scale
newborn screening pilot program between October 2005 and March 2007. The
screening involved measuring acid alpha-glucosidase activity in dried blood spots
of approximately 45% of newborns in Taiwan. The unscreened population was
monitored as a control. RESULTS: Of the 132 538 newborns screened, 1093
(0.82%) repeat dried blood-spot samples were requested and retested, and 121
(0.091%) newborns were recalled for additional evaluation. Pompe disease was
confirmed in 4 newborns. This number was similar to the number of infants who
received a diagnosis of Pompe disease in the control group (n = 3); however,
newborn screening resulted in an earlier diagnosis of Pompe disease: patients
were <1 month old compared with 3 to 6 months old in the control group.
CONCLUSIONS: To our knowledge, this is the first large-scale study to show
that newborn screening for Pompe disease is feasible. Newborn screening allows
for earlier diagnosis of Pompe disease and, thus, for assessment of the value of an
earlier start of treatment.
Acta Otolaryngol. 2008 Jun 18:1-8. [Epub ahead of print]
Universal newborn hearing screening programs in Italy: survey of year 2006.
Bubbico L, Tognola G, Greco A, Grandori F.
Department of Otolaryngology, Italian Institute of Social Medicine, Rome, Italy.
Conclusion.Our results suggest a rapid diffusion of newborn hearing screening
programs in Italy and indicate that three conditions seem to play a crucial role in
the implementation of Universal Newborn Hearing Screening (UNHS) programs:
the size (>800 births/year) and location (metropolitan urban areas) of the hospital,
and the presence of an audiologist in the UNHS coordinating team Objectives.
The aim of this paper is to provide data on the degree of implementation and
coverage of UNHS programs in Italy Materials and methods. Data were collected
through a Screening Survey Questionnaire that was sent to all birthing hospitals
active in Italy in 2006 and was filled in by the chief of the hospital or by the
UNHS program coordinator Results. In Italy UNHS coverage had undergone a
steep increase from 29.3% in 2003 (156 048 newborns screened) to 48.4% in
2006 (262 103 screened). The majority of UNHS programs were implemented in
the two most economically developed areas, i.e. in the north-west area (79.5%,
108 200 of 136 109 births), and in the north-east area (57.2%, 52 727 of 92 133
births), while a limited diffusion still remains in some areas, typically in the
islands (11.3%, 7158 of 63 460 births).
J Paediatr Child Health. 2008 Jun 12. [Epub ahead of print]
Coverage of the Victorian newborn screening programme in 2003: A
retrospective population study.
Jaques AM, Collins VR, Pitt J, Halliday JL.
Public Health Genetics, Murdoch Childrens Research Institute, Royal Children's
Hospital, Parkville, Victoria, Australia.
Objective: To assess the coverage of the newborn screening (NBS) program in
Victoria, Australia, and identify potential predictors of not being screened.
Setting: Victoria, Australia, 2003. The Victorian NBS program screens for
phenylketonuria (PKU), cystic fibrosis, congenital hypothyroidism and more than
20 metabolic conditions, such as medium chain acyl-coenzyme A dehydrogenase
(MCAD) deficiency. Methods: Victorian birth records (n = 63,018) were linked to
Victorian NBS records (n = 62,876) using probabilistic record linkage. Binary
logistic regression was used to identify potential predictors of not being screened.
Results: Uptake of NBS was 99.4% (62,643/63,018), resulting in 0.6% (375) of
livebirths not matched to a NBS test. Neonatal death was the most significant
factor associated with not being screened (relative risk (RR) = 407, 95%Cl = 314
to 526). After adjustment, surviving livebirths had an increased likelihood of not
being matched to a NBS record if they: were transferred between hospitals (odds
ratio (OR) = 2.4, 95% confidence interval (Cl) 1.5 to 3.9); were born at home (OR
= 12.1, 95%Cl 6.3 to 23.3); resided in rural Victoria (OR = 2.6, 95%Cl 1.5 to
4.3); stayed in hospital for one day or less (OR = 4.6, 95%Cl 2.8 to 7.6); or whose
mothers were primiparous (OR = 1.5, 95%Cl 1.1 to 2.1). Conclusion: NBS uptake
is extremely high in Victoria with over 99% of livebirths screened. Particular risk
factors for not having NBS have now been identified, which could lead to changes
around monitoring neonates who are not born in a hospital, or leave/transfer
hospital, before the NBS period (48-72 hours). Future studies could determine
whether those not screened had opted-out or were not offered NBS.
Creat Nurs. 2008;14(2):75-81.
Advocating for universal newborn hearing screening.
Hollenbeck L.
Children's Hospitals and Clinics of Minnesota, USA.
lani.hollenbeck@childrensmn.org
Universal newborn hearing screening and follow-up is an important detection and
intervention program promoting childhood development and the acquisition of
fundamental language, social, and cognitive skills. These skills provide the basis
for later success in school and in society. Nursing has an important role to play in
advocating for newborn hearing screening and in supporting families throughout
the screening process.
PMID: 18655518 [PubMed - in process]