Genetic etiology and pregnancy outcomes of abnormal fluid accumulation in fetus: A retrospective cohort study

Abstract

Background This study investigated the genetic etiology of abnormal fetal fluid accumulation, aiming to quantify pathogenic variants and correlate them with clinical outcomes to improve genetic counseling. Methods A cohort of 305 fetuses underwent single-nucleotide polymorphism array (SNP-array) and whole-exome sequencing (WES) of amniotic fluid or cord blood. Results Pathogenic copy number variations (CNVs) were detected in 49 cases, including aneuploidies (e.g., trisomy 21, Turner syndrome) and microdeletions/duplications. Two single-gene mutations (SNAP25, PLD1) were identified in CNV-negative cases. Non-immune hydrops (NIHF) exhibited the highest pathogenic rate (42.7%, 32/75), with non-isolated NIHF (50.0%) showing significantly higher detection than isolated NIHF (17.6%). NIHF also had the highest termination rate and postnatal abnormality rate (11%). Pleural and pericardial effusions followed in severity. Interpretation The findings demonstrate that SNP-array and WES effectively diagnose genetic causes of fluid accumulation. While some NIHF cases may have favorable outcomes, the high termination and abnormality rates underscore its generally poor prognosis. These results emphasize the importance of comprehensive prenatal genetic testing and individualized counseling for families facing such diagnoses.