Untargeted metabolomic profiles of air pollution exposure during pregnancy and postpartum depression risk: a pilot study

Abstract

Background. Postpartum depression (PPD) impacts 18% of mothers globally, adversely affecting the health of mothers and children. Evidence from the Programming Research on Obesity, Growth, Environment, and Social Stress (PROGRESS) cohort in Mexico City suggests that exposure to air pollution, namely PM2.5 (particulate matter < 2.5 μm in diameter), in pregnancy is associated with increased PPD risk. Untargeted metabolomics, in which hundreds to thousands of metabolites are identified without specifying these metabolites a priori, offers a data-driven approach to identify mechanisms linking PM2.5 and PPD.Aim. To characterize metabolomic profiles associated with PM2.5 exposures and PPD in maternal serum collected during the second and third trimesters of pregnancy.Methods. We randomly selected 100 mothers from PROGRESS in a pilot study, estimated PM2.5 exposures during pregnancy using a satellite-based spatiotemporally-resolved prediction model, and measured maternal depression at 6 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS). In maternal serum, we performed liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomic profiling of polar, semi-polar, and non-polar metabolites.Results. After filtering, 202 putatively-identified metabolites were analyzed in linear models adjusted for maternal age, education, BMI, and laboratory batch. Of these, 20 and 29 metabolites in the second and third trimesters, respectively, were associated (p<0.05) with average trimester PM2.5 levels in the respective trimester. Two third trimester metabolites (itaconate and nervonate) passed multiple testing correction (FDR<0.05). Itaconate was also negatively associated with PM2.5 in second trimester (p=0.003) and marginally associated with lower PPD risk (EPDS ≥ 13; p=0.08).Conclusions. In maternal serum collected during pregnancy, we identified metabolites associated with PM2.5 exposure. Itaconate, which was negatively associated with both PM2.5 exposure and PPD, is a mitigator of inflammation and oxidative stress, consistent with processes known to be involved in both PM2.5 exposure and depression.