Genomic and Multi-Omic Technologies Transforming Perinatal Medicine: A Systematic Review and Translational Roadmap

Genomic and multi-omic technologies are rapidly reshaping the landscape of perinatal medicine, offering unprecedented opportunities to understand maternal, placental, and fetal biology with molecular precision. This systematic review synthesizes evidence from 36 studies identified through a comprehensive PRISMA-guided search across major databases and clinical trial registries. The included literature spans whole-genome and whole-exome sequencing, bulk and single-cell transcriptomics, spatial omics, epigenomics, proteomics, metabolomics, liquid biopsy platforms, and emerging AI-integrated analytic approaches. Together, these technologies illuminate key biological pathways involved in pregnancy health and disease, including placental vascular remodeling, immune adaptation, oxidative stress, epithelial–mesenchymal transitions, and neurodevelopmental signaling. Across studies, multi-omic profiling improves diagnostic yield for fetal anomalies, enhances prediction of preeclampsia and preterm birth, and offers new insight into long-term outcomes such as the placenta–brain axis in extremely preterm infants. Although many platforms show strong mechanistic validity, clinical translation remains uneven, with several technologies limited by sample heterogeneity, modest cohort sizes, incomplete annotation pipelines, and variable reporting quality. Risk-of-bias appraisal revealed moderate methodological concerns across much of the literature, underscoring the importance of integrated analytic frameworks and standardized reporting. The collective evidence supports a staged roadmap in which discovery-level omics feed into robust bioinformatic pipelines, validated biomarkers, and decision-support tools tailored for maternal–fetal care. Ethical and equity considerations—particularly related to consent, data governance, and access to high-cost technologies—remain central to responsible implementation. This review highlights the substantial progress achieved to date and outlines future directions required to integrate multi-omic approaches into global perinatal practice.