Genetic diagnosis in fetuses with biliary tract system abnormalities: a meta-analysis and systematic review

Biliary tract system (BTS) anomalies in fetuses are rare, but carry a wide range of clinical prognoses. The present meta-analysis aims to determine the prevalence and spectrum of genetic etiologies in fetuses with BTS anomalies and evaluate their clinical implications. PubMed and Ovid Medline were searched up to June 2025. Studies reporting prenatal genetic results and outcomes of fetuses with BTS anomalies were included. The spectrum of genetic etiologies detected across included studies was systematically summarized. Pooled prevalence of genetic etiology was calculated using random-effects models, with stratified analyses by isolation status, associated anomaly types, specific BTS phenotypes, genetic testing methods, and abnormality categories. We also assessed the incidence of biliary atresia (BA) in fetuses with normal genetic test results. Seventeen studies comprising 1,105 fetuses were included. The pooled prevalence of genetic etiology was 9.1% (95% CI, 3.3–16.4%). The risk differed sharply between isolated versus nonisolated status: 0% (95% CI, 0.0-0.2%) in isolated and 32.6% (95% CI, 18.1–48.6%) in nonisolated cases. Among genetically positive cases, numerical chromosomal abnormalities (including aneuploidies and triploidies) accounted for 41.3% (mainly trisomy 18), chromosomal structural abnormalities (including copy number variations, CNVs) accounted for 33.6%, and monogenic disorders (e.g., cystic fibrosis, CF) for 25.0%. The detection rate was higher with chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq) than with karyotype alone (13.5% vs. 9.4%). In fetuses with normal genetic results, postnatal BA occurred in 1.1% (95% CI, 0.0%-8.5%) of the nonisolated group and 0.0% (95% CI, 0.0%-1.3%) of the isolated group. In fetal BTS anomalies, genetic risk depends largely on associated findings. The 0% diagnostic yield in isolated cases comes mainly from karyotyping and CMA; sequencing was rarely used, so rare monogenic disorders cannot be fully excluded. Nonisolated cases carry a high probability of genetic anomalies and benefit from genetic evaluation. Postnatal surveillance for BA is still needed even with normal genetic results. Not applicable. This systematic review and meta-analysis was registered in PROSPERO (CRD420251128401).