Abstract
Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we conducted a comprehensive literature review. We searched MEDLINE (OVID), Embase (Elsevier), Web of Science (Clarivate), and Cochrane Library (Wiley) for relevant studies published through March 2025, focusing on metabolomic profiling of pregnancies affected by fetal structural anomalies or genetic disorders. While metabolomics is a promising tool in prenatal screening and diagnosis, its integration into clinical practice remains limited.