Placental biology links genetic, epigenetic, ancestral, and social determinants to maternal–fetal health inequities

Black and African American women in the United States experience disproportionately high rates of maternal and infant mortality and morbidity, including placenta-mediated complications such as preeclampsia, preterm birth, and miscarriage. These inequities arise from the interaction of social and environmental conditions with biological pathways that become embedded over the life course, with the placenta serving as a central mediator. In this review, we examine how placental biology integrates genetic variation, epigenetic regulation, paternal contributions, immune processes, and lived social context to shape pregnancy outcomes. We synthesize evidence showing that placental dysfunction, particularly immune dysregulation driven by infectious, environmental, and psychosocial stressors, contributes to placenta-mediated complications with disproportionate impacts among African American women. We highlight how reliance on racial categories in U.S. biomedical research can obscure biological inference and argue for ancestry-informed approaches, alongside self-identified ethnicity, to disentangle inherited genetic variation from socially patterned exposures. Surveying published genome-wide association studies, we show that underrepresentation of African-ancestry populations remains a major constraint on discovery and translation in pregnancy genomic research. We further describe how placental epigenetic mechanisms link socioeconomic and environmental exposures to fetal development, placental aging, and long-term maternal-child health. Finally, we discuss how pregnancy and placental datasets remain sparse and fragmented, and consider how machine-learning approaches may improve pregnancy risk prediction when designed with equity in mind, by integrating placental multi-omics, ancestry-aware genomics, clinical data, and social determinants. Together, this review positions the placenta as a critical interface through which structural inequities shape maternal-fetal health and identifies priorities for more inclusive and equitable research and health care.