Prenatal chemical exposures and fetal growth: a narrative review of gene-environment interactions (2025)

Prenatal exposure to lifestyle-related and environmental chemicals has been increasingly associated with adverse birth outcomes. We previously reported associations between maternal and child genetic polymorphisms and such exposures during pregnancy, focusing on active and passive smoking. This review explores how adverse maternal exposures to such chemicals, influence birth outcomes through gene-environment interactions, excluding active and passive smoking during pregnancy. Focusing on epidemiological studies, we examined the association of gene-environment interactions with maternal lifestyle-related chemicals and environmental chemicals during pregnancy on birth outcomes. Most studies were prospective birth cohorts. While genetic polymorphisms in the cytochrome P450 (CYP) and glutathione S-transferase (GST) gene families have been previously investigated, gene polymorphisms related to receptors, transporters, and signal transduction have also been examined in both mother and children. Many reports indicate significant gene-environment interactions between lifestyle-related chemicals and environmental chemicals on birth outcomes. However, the results regarding gene-environment interactions were inconsistent. Recently, new genetic polymorphisms interacting with various chemicals have been identified in epidemiological studies. Further gene-environment interaction studies are needed to better understand the genetic and biological pathways that influence the association between lifestyle-related and environmental chemical exposures during pregnancy and birth outcomes. IMPACT: Summarizes current evidence on how maternal and child genetic polymorphisms modify the effects of prenatal chemical exposures on birth outcomes. Highlights emerging genetic variants that may alter susceptibility to lifestyle-related and environmental chemicals during pregnancy. Underscores the need for further research to clarify biological pathways and guide strategies to better protect maternal and child health.