Translational Genomics Across the Maternal–Fetal–Neonatal Continuum: A Systematic Review and Roadmap for Personalized Pregnancy Care and Neonatal Precision Medicine

Abstract Translational genomics is reshaping the landscape of maternal, fetal, and neonatal medicine, yet the field remains fragmented across clinical stages and technology platforms. This systematic review synthesizes contemporary evidence to construct a unified framework spanning preconception biology, prenatal diagnostics, fetal development, neonatal critical care, and long-term health trajectories. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines, we systematically searched major bibliographic databases and research registries, screened 1668 records, and included 45 studies covering genome sequencing, multiomics, bioinformatics workflows, ethical governance, and clinical implementation. The literature reveals a rapidly advancing ecosystem in which non-invasive sequencing, prenatal exome and genome testing, emerging biosensors, developmental and epigenomic signatures, and rapid whole-genome sequencing in the neonatal intensive care unit converge to support precision care across the maternal–fetal–neonatal continuum. Robust insights are emerging regarding maternal–fetal genetic partitioning, polygenic contributions to pregnancy complications, environmentally induced epigenetic remodeling, and the diagnostic and management impact of prenatal and neonatal sequencing. However, translation into practice remains uneven, challenged by limited validation, disparities in access, interpretive uncertainty, and variable readiness of health-system infrastructures. This review integrates mechanistic and clinical findings into a structured roadmap, emphasizing the need for harmonized workflows, multiomic data integration, artificial intelligence-assisted interpretation, and ethical frameworks that support equitable implementation. The synthesis highlights tangible opportunities for transforming prenatal risk assessment, fetal therapy, neonatal critical care, and newborn screening through genomically informed decision-making. Together, these insights outline a forward-looking model for delivering personalized pregnancy care and precision neonatology grounded in rigorous evidence and translational readiness.