Abstract
Fetal digestive system malformations (DSMs) are correlated with chromosomal anomalies. The prenatal diagnosis of DSMs allows for timely treatment and reduces perinatal morbidity and mortality. However, genetic screening for fetal DSMs is rarely reported. This study aimed to investigate genetic etiology and pregnancy outcomes in cases of fetal DSM by analyzing correlations between DSM types and chromosomal anomalies. This retrospective single-center study included 126 fetuses in whom DSMs were detected via prenatal ultrasonography. Genetic etiology was investigated using conventional karyotyping, chromosome microarray analysis (CMA), and whole-exome sequencing (WES). DSMs were categorized as simple DSM (Group A), DSM combined with abnormal ultrasound soft markers (Group B), and DSM combined with comorbidities of other systems (Group C). Abnormal karyotypes were detected in 11/126 (8.7 %) fetuses. Four more pathogenic copy number variants (CNVs) were detected using CMA, increasing the detection rate to 11.9 %. The detection rates significantly differed between the three DSM types (1.78 %, 8.11 %, and 33.33 % in Groups A, B, and C, respectively). The overall adverse pregnancy outcome rate was 33.9 %, and 11.5 %, 23.5 %, and 81.3 %, (P < 0.001), respectively, in Groups A, B, and C. Out of 83 live births, three neonates died, 26 underwent postnatal surgery with 24 favorable outcomes, and 54 did not undergo surgery and were basically normal. Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively. Our findings demonstrate that fetal DSM is closely related to chromosome aneuploidies, CNVs, and point mutations. The prognoses of most fetuses with simple DSM and those with comorbid abnormal ultrasound soft markers were favorable in the absence of chromosomal anomalies and severe structural malformations, provided they underwent timely surgery as neonates. These findings provide guidance for the prenatal diagnosis and clinical management of fetal DSMs and the genetic counseling of parents.