Air pollution exposure during pregnancy and placental metabolomics

Background and aim: Prenatal exposure to air pollution has been shown to adversely affect birth outcomes and child health. But few studies have applied metabolomics approach to understand the relevant biological mechanisms. We aim to investigate the metabolomic profiling in the placenta associated with prenatal air pollution exposure. Methods: This pilot analysis included twenty healthy, non-smoking pregnant women delivered at Anzhen Hospital in Beijing, China in 2017. Untargeted metabolomic profiling was performed on maternal placental tissues using UPLC-MS/MS. Maternal exposure to PM2.5 throughout pregnancy at residential and working addresses was estimated by a high-resolution hybrid spatiotemporal model. Linear regression and pathway enrichment analysis were performed to identify metabolites and metabolic pathways associated with trimester-specific and whole-pregnancy air pollution exposure, adjusting for maternal age, gestational age, pre-pregnancy BMI, and diet. Results: The means (SDs) of PM2.5 levels in the first, second, and third trimester, and the whole pregnancy were 107.6 (28.7), 64.3 (11.3), 53.3 (5.8), and 73.5 (12.1) µg/m3, respectively. A total of 897 known compounds were identified from the placental tissues. PM2.5 exposure during the first trimester was associated with changes in 65 metabolites in placental samples, but none remained significant after multiple comparisons (the false discover rate [FDR] at 0.05). We identified three placental metabolic pathways significantly associated with PM2.5 exposure in the first trimester, including valine, leucine and isoleucine biosynthesis (FDR <0.001), aminoacyl-tRNA biosynthesis (FDR =0.003), and arginine biosynthesis (FDR =0.006). We did not observe significant changes in individual metabolites or metabolic pathways in response to PM2.5 exposure in other two trimesters or during the whole pregnancy. Conclusion: Prenatal exposure to air pollution might affect amino acids metabolism in the placenta and more studies are needed to further elucidate underlying mechanisms. Keyword: Air pollution, Pregnancy, Metabolomics