Obstetric pharmacogenomics

Abstract

Pregnancy profoundly alters drug disposition through dynamic physiologic adaptations affecting absorption, distribution, metabolism, and excretion. Although pharmacogenomics has transformed precision therapeutics across multiple medical specialties, its application during pregnancy remains limited because conventional pharmacogenomic models assume stable genotype-phenotype relationships that do not account for the temporal biologic changes of gestation. This mini-review proposes a conceptual framework for obstetric-pharmacogenomics in which maternal, placental, and fetal-genomes interact within a continuously evolving physiologic environment to shape drug exposure, therapeutic efficacy, and toxicity. Pregnancy-induced alterations in cytochrome P450 enzyme activity, drug transporters, placental metabolism, and immune regulation may amplify, attenuate, or fundamentally modify genetically determined drug responses, rendering static pharmacogenomic classifications insufficient. We discuss the clinical implications of this dynamic paradigm across several therapeutic areas, including antiretroviral therapy, maternal mental health, hypertensive disorders of pregnancy, and analgesia, and highlight the need for trimester-specific approaches to individualized drug therapy. We further examine current barriers to implementation, including the exclusion of pregnant women from pharmacogenomic research, limited longitudinal data, and ethical considerations surrounding fetal genetics. Integrating pharmacogenomics with physiologically based pharmacokinetic modeling and multi-omics technologies offers an opportunity to redefine precision-medicine in obstetrics and advance safer, more effective, and individualized pharmacotherapy for pregnant-women and their offspring.