目的：探讨胎儿中枢神经系统(CNS)异常的遗传病因及妊娠结局。
方法：从2016年1月至2022年12月，我们纳入了217例中枢神经系统异常的胎儿。124例接受了核型分析，73例同时接受了拷贝数变异测序（CNV-seq）。随访动态超声筛查及妊娠结局,包括新生儿神经发育结果。
结果：（1）超声显示20种类型的中枢神经系统异常，最常见的是脑室增宽。(2)124例中14例(11.3%)通过核型分析发现染色体异常,通过CNV-seq在73例中的13例（17.8％）中发现了拷贝数变异（CNV）。非孤立性中枢神经系统异常的胎儿异常核型和CNV的检出率（DR）高于孤立性中枢神经系统异常的胎儿（25.0％vs.4.8%；35.0%与11.3%)(P<0.05)。多重CNS异常的异常核型DR明显高于单一CNS异常（16.7％vs.2.8%，P<0.05),而CNVs的DR没有显着差异。（3）通过动态超声，12例进一步发现进展或其他畸形。(4)209例获得妊娠结局,包括136例(65.1%)活产,3例（1.4%）胎儿宫内死亡，和70（33.5％）终止。经过长期随访，最终发现了2名新生儿在6个月时死亡，一名患有运动和智力残疾的婴儿。
结论：基因分析结合动态超声筛查和多学科会诊对评估胎儿中枢神经系统异常的预后具有重要作用。特别是对于有多个中枢神经系统或颅外异常的人。
OBJECTIVE: 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.
CONCLUSIONS: 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.
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