Per- and polyfluoroalkyl substances (PFASs) exposure is ubiquitous among the US population and has been linked to adverse health outcomes including cardiometabolic diseases, immune dysregulation and endocrine disruption. However, the metabolic mechanism underlying the adverse health effect of PFASs exposure is unknown. The aim of this project is to investigate the association between PFASs exposure and altered metabolic pathways linked to increased cardiometabolic risk in young adults. A total of 102 young adults with 82% overweight or obese participants were enrolled from Southern California between 2014 and 2017. Cardiometabolic outcomes were assessed including oral glucose tolerance test (OGTT) measures, body fat and lipid profiles. High-resolution metabolomics was used to quantify plasma exposure levels of three PFAS congeners and intensity profiles of the untargeted metabolome. Fasting concentrations of 45 targeted metabolites involved in fatty acid and lipid metabolism were used to verify untargeted metabolomics findings. Bayesian Kernel Machine Regression (BKMR) was used to examine the associations between PFAS exposure mixture and cardiometabolic outcomes adjusting for covariates. Mummichog pathway enrichment analysis was used to explore PFAS-associated metabolic pathways. Moreover, the effect of PFAS exposure on the metabolic network, including metabolomic profiles and cardiometabolic outcomes, was investigated. Higher exposure to perfluorooctanoic acid (PFOA) was associated with higher 30-minute glucose levels and glucose area under the curve (AUC) during the OGTT (p < 0.001). PFAS exposure was also associated with altered lipid pathways, which contributed to the metabolic network connecting PFOA and higher glucose levels following the OGTT. Targeted metabolomics analysis indicated that higher PFOA exposure was associated with higher levels of glycerol (p = 0.006), which itself was associated with higher 30-minute glucose (p = 0.006). Increased lipolysis and fatty acid oxidation could contribute to the biological mechanisms linking PFAS exposure and impaired glucose metabolism among young adults. Findings of this study warrants future experimental studies and epidemiological studies with larger sample size to replicate.

Air pollution has been associated with gestational diabetes mellitus (GDM). We aim to investigate susceptible windows of air pollution exposure and factors determining population vulnerability. We ascertained GDM status in the prospective Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort from Los Angeles, California, USA. We calculated the relative risk of GDM by exposure to ambient particulate matter (PM₁₀; PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) in each week from 12 weeks before to 24 weeks after conception, adjusting for potential confounders, with distributed lag models to identify susceptible exposure windows. We examined effect modification by prenatal depression, median-split pre-pregnancy BMI (ppBMI) and age. Sixty (9.7%) participants were diagnosed with GDM among 617 participants (mean age: 28.2 years, SD: 5.9; 78.6% Hispanic, 11.8% non-Hispanic Black). GDM risk increased with exposure to PM_2.5, PM₁₀, and NO₂ in a periconceptional window ranging from 5 weeks before to 5 weeks after conception: interquartile-range increases in PM_2.5, PM₁₀, and NO₂ during this window were associated with increased GDM risk by 5.7% (95% CI: 4.6–6.8), 8.9% (8.1–9.6), and 15.0% (13.9–16.2), respectively. These sensitive windows generally widened, with greater effects, among those with prenatal depression, with age ≥28 years, or with ppBMI ≥27.5 kg/m², than their counterparts. Preconception and early-pregnancy are susceptible windows of air pollutants exposure that increased GDM risk. Prenatal depression, higher age, or higher ppBMI may increase one’s vulnerability to air pollution-associated GDM risk. 10.13039/100000002 National Institutes of Health , 10.13039/501100001589 Environmental Protection Agency .

BACKGROUND: Air pollution has been associated with gestational hypertension (GH) and preeclampsia, but susceptible windows of exposure and potential vulnerability by comorbidities, such as prenatal depression, remain unclear. METHODS: We ascertained GH and preeclampsia cases in a prospective pregnancy cohort in Los Angeles, CA. Daily levels of ambient particulate matters (with a diameter of ≤10 μm [PM ₁₀ ] or ≤2.5 μm [PM _2.5 ]), nitrogen dioxide, and ozone were averaged for each week from 12 weeks preconception to 20 gestational weeks. We used distributed lag models to identify susceptible exposure windows, adjusting for potential confounders. Analyses were additionally stratified by probable prenatal depression to explore population vulnerability. RESULTS: Among 619 participants, 60 developed preeclampsia and 42 developed GH. We identified a susceptible window for exposure to PM _2.5 from 1 week preconception to 11 weeks postconception: higher exposure (5 µg/m ³ ) within this window was associated with an average of 8% (95% CI, 1%–15%) higher risk of GH. Among participants with probable prenatal depression (n=179; 32%), overlapping sensitive windows were observed for all pollutants from 8 weeks before to 10 weeks postconception with increased risk of GH (PM _2.5 , 16% [95% CI, 3%–31%]; PM ₁₀ , 39% [95% CI, 13%–72%]; nitrogen dioxide, 65% [95% CI, 17%–134%]; and ozone, 45% [95% CI, 9%–93%]), while the associations were close to null among those without prenatal depression. Air pollutants were not associated with preeclampsia in any analyses. CONCLUSIONS: We identified periconception through early pregnancy as a susceptible window of air pollution exposure with an increased risk of GH. Prenatal depression increases vulnerability to air pollution exposure and GH.

Breastfeeding may protect women’s long-term cardiovascular health; however, breastfeeding-related postpartum lipid changes remain unclear. We aim to examine associations of breastfeeding duration with maternal lipids at 12 months postpartum. In a subsample (n = 79) of the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, breastfeeding status and duration at 3, 6, and 12 months postpartum were self-reported. Serum levels of lipids, including total cholesterol, triglycerides (TG), high-, low-, and very low-density lipoprotein cholesterol (HDL-C, LDL-C, VLDL-C), were measured from blood samples collected at 12 months postpartum. We used linear regression models to compare lipids by breastfeeding duration, adjusting for potential confounders. Women who were breastfeeding at 12 months had higher HDL-C (mean: 41.74 mg/dL, 95% CI: 37.27–46.74 vs. 35.11 mg/dL, 95% CI: 31.42–39.24), lower TG (80.45 mg/dL, 95% CI: 66.20–97.77 vs. 119.11 mg/dL, 95% CI: 98.36–144.25), and lower VLDL-C (16.31 mg/dL, 95% CI: 13.23, 20.12 vs. 23.09 mg/dL, 95% CI: 18.61–28.65) compared to women who breastfed for <6 months. No lipids were significantly different between women who breastfed for 6–11 months and for <6 months. Each month’s increase in breastfeeding duration was significantly, inversely associated with TG and VLDL-C and positively with HDL-C. Adjusting for fasting status, demographics, pre-pregnancy body mass index, breastfeeding frequency, and pregnancy complications did not appreciably change effect estimates. Breastfeeding at 12 months postpartum and a longer duration of breastfeeding in the first year postpartum were both associated with increased HDL-C and decreased TG and VLDL-C at 12 months postpartum.