Prenatal and postnatal findings in small-for-gestational-age fetuses without structural ultrasound anomalies at 18-24 weeks.
OBJECTIVE
To assess phenotypic and genotypic characteristics of small-for-gestational-age (SGA) fetuses without structural anomalies at 18-24 weeks' gestation.


METHODS
This retrospective study included structurally normal singleton fetuses with an abdominal circumference ≤ 5thpercentile on detailed ultrasound examination between 18 and 24 weeks' gestation. Cases were stratified according to the absence or presence of other abnormal ultrasound findings, such as abnormal amniotic fluid or soft markers. All patients were offered invasive prenatal testing with rapid aneuploidy detection by qualitative fluorescence polymerase chain reaction (QF-PCR) and, if normal, consecutive single nucleotide polymorphism (SNP) array was also offered. Detailed postnatal follow-up (≥ 5 months) was performed. In cases in which a syndromic phenotype became apparent within 5 months after birth and SNP array had not been performed prenatally, it was performed postnatally.


RESULTS
A total of 211 pregnancies were eligible for inclusion. Of the 158 cases with isolated SGA on ultrasound, 36 opted for invasive prenatal testing. One case of trisomy 21 and one case of a submicroscopic abnormality (a susceptibility locus for neurodevelopmental disease) were detected. Postnatal follow-up showed a postnatal apparent syndromic phenotype in 10 cases. In one case this was due to trisomy 21 and the other nine (5.8%; 95% CI, 2.8-10.0%) cases had normal SNP array results. In 32/53 cases with SGA and associated ultrasound abnormalities, parents opted for invasive testing. One case of trisomy 21 and one of triploidy were found. In 11 cases a syndromic phenotype became apparent after birth. One was due to trisomy 21 and in one case a submicroscopic anomaly (a susceptibility locus) was found. The remaining syndromic cases (17.3%; 95% CI, 8.7-29.0%) had normal SNP array results.


CONCLUSIONS
Testing for chromosomal anomalies should be offered in cases of SGA between 18 and 24 weeks' gestation. Whole chromosome anomalies occur in 1.3% (95% CI, 0.2-3.9%) of isolated SGA and 5.8% (95% CI, 1.5-14.0%) of associated SGA. In 0.6% (95% CI, 0.1-2.8%) and 1.9% (95% CI, 0.2-8.2%), respectively, SNP array detected a susceptibility locus for neurodevelopmental disease that would not be detected by karyotyping, QF-PCR or non-invasive prenatal testing. Therefore, and because the genetic causes of SGA are diverse, we suggest SNP array testing in cases of SGA. Thorough postnatal examination and follow-up of infants that presented with reduced fetal growth is important because chromosomally normal syndromic phenotypes occur frequently in SGA fetuses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
M C
MC
de Wit
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
M I
MI
Srebniak
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
M
M
Joosten
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
L C P
LC
Govaerts
Department of Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands.
R F
RF
Kornelisse
Department of Obstetrics and Gynecology, Amphia Hospital, Breda, The Netherlands.
D N M
DN
Papatsonis
Department of Obstetrics and Gynecology, Reinier de Graaf Groep, Delft, The Netherlands.
K
K
de Graaff
Foundation Prenatal Screening Southwestern region of The Netherlands, Rotterdam, The Netherlands.
M F C M
MF
Knapen
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
H T
HT
Bruggenwirth
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
F A T
FA
de Vries
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
S
S
Van Veen
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
D
D
Van Opstal
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
R J H
RJ
Galjaard
Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
A T J I
AT
Go
D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D049628:Body Size; D002869:Chromosome Aberrations / Q000706:statistics & numerical data*; D005260:Female; D020567:Fetal Weight / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008423:Maternal Age; D010641:Phenotype; D011181:Postnatal Care; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D014463:Ultrasonography / Q000379:methods*; D016216:Ultrasonography, Prenatal / Q000379:methods; D055815:Young Adult
SGA; SNP array; fetal growth; microarray; prenatal diagnosis