Particulate Air Pollution Exposure during Pregnancy and Mitochondrial-Associated Plasma Metabolites in Mothers at 48 Months Postpartum: A Pilot Study

摘要

Background Pregnancy and early postpartum life are periods of major metabolic change in women and may be critical windows of susceptibility for longer-term metabolic changes induced by inflammatory exposures, such as PM2.5 (ambient particulate matter <2.5 μm in diameter). Hypothesis As mitochondria are sensitive to inflammation, we hypothesized that gestational/early postpartum PM2.5 exposure would predict metabolomic profiles of small molecules in mitochondrial-associated pathways measured years after pregnancy. Methods In a pilot study, we randomly selected 50 mothers from the Programming Research on Obesity, GRowth, Environment and Social Stress (PROGRESS) cohort based in Mexico City. We estimated PM2.5 exposure using a satellite-based spatiotemporally-resolved prediction model. In maternal plasma collected at 48 months postpartum, we assessed 110 metabolites in mitochondrial pathways (TCA cycle, fatty acid p5-oxidation, and branched chain amino acid catabolism) using Metabolon's Discovery HD4T platform. Results In robust regression models adjusted for age, secondhand smoke exposure, socioeconomic status, alcohol consumption, and parity, average PM2.5 during the first year postpartum was associated with 17 metabolites (p<0.05). The majority were long chain fatty acids and polyunsaturated fatty acids, which were negatively associated with PM2.5 No associations were observed for these fatty acids with average PM2.5 during pregnancy. Further, fewer metabolites overall were associated with PM2.5 during pregnancy (two at p<0.05), suggesting results vary by time of exposure. Conclusion In this pilot study, we found that PM2.5 exposure during the first year postpartum was associated with altered fatty acid metabolism in plasma from mothers at 48 months postpartum. The postpartum period may be a susceptibility window for PM2.5 exposure with regard to metabolic dysregulation, particularly lipids. We plan to replicate these findings in the full sample and in independent cohorts.