Oxidative Stress-Related Metabolomic Alterations in Pregnancy: Evidence from Exposure to Air Pollution, Metals/Metalloid, and Tobacco Smoke.

Developmental programming, shaped by environmental and lifestyle stressors during prenatal life, is increasingly recognized as a major contributor to non-communicable diseases (NCDs) later in life. Oxidative stress, one of key mechanisms linking these stressors to fetal metabolomic reprogramming and disease pathogenesis, leaves measurable metabolomic signatures that reflect disrupted redox balance. Alterations in glucose, lipid, and amino acid metabolism and antioxidant response could reveal the main pathways driving NCD development. This review summarizes epidemiological studies that have investigated biochemical responses of the prenatal exposure to metals, air pollution, and tobacco smoke and e-cigarette vapor in maternal-placental-fetal compartments using a metabolomic approach. Summarized studies indicate that maternal exposure to metals primarily disrupts amino acid pathways related to one-carbon metabolism, glutathione synthesis, and oxidative stress defense, while air pollution, particularly fine particulate matter, mainly affects lipid oxidation, fatty acid β-oxidation, and amino acid and carbohydrate metabolism. Tobacco smoke and e-cigarette vapor induce widespread disturbances involving reduced citric acid cycle intermediates, altered acylcarnitines and phospholipids, and impaired antioxidant capacity, collectively promoting oxidative damage and inflammatory signaling. The identification of these metabolome alterations might contribute to a deeper understanding of the toxicity and biological impact of environmental stressors on offspring health. These results may eventually lead to the identification of early biomarkers and to the development of therapeutic strategies aimed at reducing NCD risk.