Trimester-Specific Associations of Prenatal Heat Exposure with Neonatal Amino Acid and Acylcarnitine Profiles

Abstract It remains unclear whether prenatal heat exposure is associated with newborn metabolic profiles. Therefore, based on 4714 mother–infant pairs in Shanghai, we aimed to investigate the trimester-specific associations of prenatal heat exposure with neonatal amino acid (AA) and acylcarnitine (AC) profiles. Heat exposure was defined using the 90th percentile of trimester-specific temperature distributions from the ERA5-Land data set. For AAs, glutamate showed consistently positive associations across three trimesters, whereas phenylalanine, tyrosine, leucine, arginine, and citrulline showed consistently negative associations; other AAs exhibited trimester-specific patterns. For ACs, C2, C4, and C16 showed consistently negative associations, while a chain-length-dependent pattern was observed: short-chain ACs were predominantly negatively associated, whereas most medium- and long-chain ACs reversed to positive associations in the second and third trimesters. Network topology analysis revealed stronger metabolite correlation structures in the heat-exposed group across all trimesters, with AA-AC pairs accounting for the largest proportion of differential correlations. Distributed lag nonlinear models suggested susceptible windows at gestational weeks 10–17 and 25–27 for AAs, and weeks 8–14 and 26–34 for ACs. Overall, prenatal heat exposure was significantly associated with multiple neonatal AAs and ACs, with distinct trimester-specific patterns and a denser intermetabolite correlation network in the heat-exposed group.