Precision Medicine in Perinatal Cardiorespiratory Disease: A Systematic Review of Multi-omics, Genetic Profiling, and Pharmacogenomics for Maternal–Fetal Risk Assessment

Abstract Growing interest in precision medicine has highlighted major gaps in how perinatal cardiopulmonary disorders are assessed and managed, particularly in pregnancies complicated by pulmonary hypertension, congenital heart disease, or placental dysfunction. Although individual studies have explored metabolomics, transcriptomics, lipidomics, and pharmacogenomics in pregnancy, these efforts remain fragmented, and no synthesis has linked multi-omic signatures to maternal cardiovascular strain or fetal vulnerability. To address this gap, we conducted a systematic review following PRISMA 2020 guidance, examining evidence across biomedical databases, registries, and scientific repositories. After removing duplicates and screening 1023 records, 41 studies met the prespecified criteria. The included data spanned clinical cohorts, multi-omic analyses, imaging-based placental studies, pharmacogenomic investigations, and multidisciplinary management reports. Across studies, consistent patterns emerged. Maternal cardiopulmonary disease was repeatedly associated with altered metabolic and lipid signatures, transcriptomic dysregulation, and impaired placental microenvironmental integrity. Multi-omics approaches revealed converging pathways involving inflammation, oxidative stress, endothelial dysfunction, and aberrant vascular remodeling. These molecular findings paralleled clinical outcomes, including heightened maternal morbidity, right-heart compromise, preterm birth, fetal growth restriction, and increased neonatal intensive care needs. Evidence on pharmacogenomic variability, although limited, suggested that genetic differences may influence response to beta-blockers, vasodilators, and anticoagulants during pregnancy. Taken together, the literature indicates that multi-omic and pharmacogenomic tools have the potential to redefine maternal–fetal risk stratification in cardiopulmonary disease, yet systematic integration into clinical practice has not occurred. This review synthesizes the emerging evidence, identifies translational opportunities, and highlights priority areas where precision-based approaches may meaningfully improve outcomes for high-risk pregnancies.