Fetal genetic findings for fetal growth restriction without structural malformations at a territory referral center: 10-year experience

Abstract

Abstract Background: Prenatal invasive genetic testing is always offered in pregnancies of FGR. The aim of this study was to explore the fetal genetic factors for FGR without structural malformations according to conventional karyotyping and single nucleotide polymorphism array (SNP array) analysis during a 10-year period. Methods:We retrospectively reviewed 488 fetuses who diagnosed with FGR and without structural malformation. Conventional karyotyping was performed on all subjects, and SNP array was performed on 272 of them. The cohort was classified into groups diagnosed at ≤24, 25-28, 29-32, and > 32 weeks of gestation. According to the ultrasonography, they were grouped into isolated FGR, FGR with soft markers, and FGR with nonstructural anomalies. Based on the maternal serum screening (MSS), they were categorized into high-risk and low-risk MSS groups. The rates of abnormal karyotypes and incremental yield of clinically significant aberrations detected by SNP array were compared among groups in different classifications. Results: According to conventional karyotyping for the whole cohort, 19 (3.9%) cases of chromosomal anomalies were detected, including 11 cases of numerical abnormalities, 5 of structural abnormalities, and 3 of mosaicism. Abnormal karyotypes were more frequently detected in cases diagnosed at ≤24 weeks (7.2%), cases with soft markers (5.2%), and cases with high-risk MSS (7.5%) than in other groups within each classification. Among cases with normal karyotype, additional 4.2% of clinically relevant aberrations were detected by SNP array. The incremental yields in cases diagnosed at ≤24 weeks (6.5%), cases with soft markers (9.5%), and cases with high-risk MSS (12.0%) were higher than those in other groups within each classification.All fetuses with abnormal karyotypes and 7 out of 11 fetuses with clinically relevant aberrations detected by SNP array only resulted in terminations of pregnancy, and the rest 4 fetuses were live born. Conclusion:Fetal chromosomal aberration is an important etiology for FGR without structural malformation, and plays an important role in pregnancies decision-making. SNP array improves the detection of genetic anomalies especially in fetuses diagnosed at ≤24 weeks, fetuses with soft makers, and fetuses with high risk of MSS.