Genetic etiology and pregnancy outcomes of fetuses with central nervous system anomalies

Abstract

Abstract Purpose To investigate genetic etiology and pregnancy outcomes of fetal central nervous system (CNS) anomalies. Methods 217 fetuses with CNS anomalies were included in our cohort from January 2016 to December 2022. 124 cases received karyotyping and 73 cases simultaneously underwent copy number variant sequencing (CNV-seq). Dynamic ultrasound screening and pregnancy outcomes were followed up, including neonates’ neurodevelopmental outcomes. Results (1) 20 types of CNS anomalies were revealed by ultrasound and the most common was ventriculomegaly. (2) 14 (11.3%) of 124 cases were found chromosomal abnormalities by karyotyping, and copy number variations (CNVs) were revealed in 13 (17.8%) of 73 cases by CNV-seq. Fetuses with non-isolated CNS anomalies had a higher detection rate (DR) of abnormal karyotypes and CNVs than those with isolated CNS anomalies (25.0% vs. 4.8%; 35.0% vs. 11.3%) (P < 0.05). And the DR of abnormal karyotypes was significantly higher in multiple CNS anomalies than in single CNS anomaly (16.7% vs. 2.8%, P < 0.05), while there were no significant differences in the DR of CNVs. (3) Through dynamic ultrasound, 12 cases were further found progression or additional malformations. (4) Pregnancy outcomes of 209 cases were obtained, including 136 (65.1%) live births, 3 (1.4%) intrauterine fetal deaths, and 70 (33.5%) terminated. Two neonatal deaths at 6 months and one infant with motor and intellectual disabilities were finally found after long-term follow-up. Conclusion Genetic analysis combined with dynamic ultrasound screening and multidisciplinary consultation plays an important role in evaluating the prognosis of fetal CNS anomalies, especially for those with multiple CNS or extracranial abnormalities.