Prenatal exposure to fine particulate matter and its components is associated with neonatal amino acids and...

The quantitative associations of prenatal exposure to fine particulate matter (PM_2.5) and its components with neonatal blood amino acid (AA) and acylcarnitine (AC) profiles, as well as the critical exposure windows, remain largely unknown. Using data from a birth cohort in Shanghai, we aimed to explore these associations in 4802 mother-infant pairs, with metabolite levels measured by liquid chromatography-tandem mass spectrometry. All neonatal metabolite levels were log-transformed and standardized. We found that per interquartile range increase in prenatal PM_2.5 exposure was significantly associated with 18 neonatal metabolites. Specifically, levels of aspartic acid (β: 0.395), glycine (β: 0.364) and medium-chain ACs (C6DC (β: 0.374), C10 (β: 0.409), C12 (β: 0.378)) were increased, while levels of arginine (β: -0.465), citrulline (β: -0.355) and short-chain ACs (C2 (β: -0.376), C3 (β: -0.349), C4 (β: -0.554)) were decreased. Pathway analysis revealed four exploratory metabolic pathway signals linked to prenatal PM_2.5 exposure: the urea cycle, oxidation of branched-chain fatty acids, arginine and proline metabolism, and aspartate metabolism. Organic matter, approximated as residual organic matter (estimated), was the major contributor among PM_2.5 components. Mid-gestation exposure showed the strongest associations with AA metabolism and the urea cycle pathways, whereas late-gestation exposure was more strongly linked to oxidation of branched-chain fatty acids. Mediation analyses suggested that, for the associations of PM_2.5 and its components with glutamine and short-chain ACs, there were possible and small mediation effects by thyroid-stimulating hormone, but results were not statistically robust. Overall, prenatal exposure to PM_2.5 was significantly associated with alterations in neonatal AAs and ACs, with residual organic matter (estimated) being the most important component of PM_2.5.