Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusions: 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.

ImportanceFetal growth is precisely programmed and could be interrupted by environmental exposures during specific times during pregnancy. Insights on potential sensitive windows of air pollution exposure in association with birth weight are needed.ObjectiveTo examine the association of sensitive windows of ambient air pollution exposure with birth weight and heterogeneity by individual- and neighborhood-level stressors.Design, Setting, and ParticipantsData on a cohort of low-income Hispanic women with singleton term pregnancy were collected from 2015 to 2021 in the ongoing Maternal and Developmental Risks from Environmental and Social Stressors cohort in Los Angeles, California.ExposuresDaily ambient particulate matter with aerodynamic diameter less than 10 μm (PM10) and aerodynamic diameter less than 2.5 μm (PM2.5), nitrogen dioxide (NO2), and 8-hour maximum ozone were assigned to residential locations. Weekly averages from 12 weeks before conception to 36 gestational weeks were calculated. Individual-level psychological stressor was measured by the Perceived Stress Scale. Neighborhood-level stressor was measured by the CalEnviroScreen 4.0.Main Outcomes and MeasuresSex-specific birth weight for gestational age z score (BWZ). The associations between air pollutant and BWZ were estimated using distributed lag models to identify sensitive windows of exposure, adjusting for maternal and meteorologic factors. We stratified the analyses by Perceived Stress Scale and CalEnviroScreen 4.0. We converted the effect size estimation in BWZ to grams to facilitate interpretation.ResultsThe study included 628 pregnant women (mean [SD] age, 22.18 [5.92] years) and their newborns (mean [SD] BWZ, −0.08 [1.03]). On average, an interquartile range (IQR) increase in PM2.5 exposure during 4 to 22 gestational weeks was associated with a −9.5 g (95% CI, −10.4 to −8.6 g) change in birth weight. In stratified models, PM2.5 from 4 to 24 gestational weeks was associated with a −34.0 g (95% CI, −35.7 to −32.4 g) change in birth weight and PM10 from 9 to 14 gestational weeks was associated with a −39.4 g (95% CI, −45.4 to −33.4) change in birth weight in the subgroup with high Perceived Stress Scale and high CalEnviroScreen 4.0 scores. In this same group, NO2 from 9 to 14 gestational weeks was associated with a −40.4 g (95% CI, −47.4 to −33.3 g) change in birth weight and, from 33 to 36 gestational weeks, a −117.6 g (95% CI, −125.3 to −83.7 g) change in birth weight. Generally, there were no significant preconception windows for any air pollutants or ozone exposure with birth weight.Conclusions and RelevanceIn this cohort study, early pregnancy to midpregnancy exposures to PM2.5, PM10, and NO2 were associated with lower birth weight, particularly for mothers experiencing higher perceived stress and living in a neighborhood with a high level of stressors from environmental pollution.

IntroductionPerfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals found in household products that can cross the placenta during pregnancy. We investigated whether PFAS exposure during pregnancy was associated with infant birth outcomes in a predominantly urban Hispanic population.MethodsSerum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 342 prenatal biospecimens (mean gestational age: 21 ± 9 weeks) from participants in the ongoing Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. PFAS compounds were modeled continuously or categorically, depending on the percentage of samples detected. The birth outcomes assessed were birthweight, gestational age at birth, and birthweight for gestational age (BW-for-GA) z-scores that accounted for parity or infant sex. Single pollutant and multipollutant linear regression models were performed to evaluate associations between PFAS exposures and birth outcomes, adjusting for sociodemographic, perinatal, and study design covariates.ResultsMaternal participants (n = 342) were on average 29 ± 6 years old at study entry and were predominantly Hispanic (76%). Infants were born at a mean of 39 ± 2 weeks of gestation and weighed on average 3,278 ± 522 g. PFOS and PFHxS were detected in 100% of the samples while PFNA, PFOA, and PFDA were detected in 70%, 65%, and 57% of the samples, respectively. PFAS levels were generally lower in this cohort than in comparable cohorts. Women with detected levels of PFOA during pregnancy had infants weighing on average 119.7 g less (95% CI −216.7, −22.7) than women with undetected levels of PFOA in adjusted single pollutant models. PFOA results were also statistically significant in BW-for-GA z-score models that were specific for sex or parity. In models that were mutually adjusted for five detected PFAS compounds, PFOA results remained comparable; however, the association was only significant in BW-for-GA z-scores that were specific for parity (β = −0.3; 95% CI −0.6, −0.01). We found no significant adjusted associations with the remaining PFAS concentrations and the birth outcomes assessed.ConclusionPrenatal exposure to PFOA was associated with lower birthweight in infants, suggesting that exposure to these chemicals during critical periods of development might have important implications for children's health.

Background Studies examining diet and its link to birth outcomes among socioeconomically disadvantaged populations in the U.S. are scarce. Objectives We aimed to identify prenatal dietary patterns, examine their relationships with birth outcomes, and evaluate the variation of these associations by maternal diabetes status (none, gestational [GDM], pre-existing). Methods Women in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study (n = 465)—an ongoing, prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles—completed up to two 24-hour dietary recalls in the third trimester of pregnancy. We identified prenatal dietary patterns (DPs) via factor analysis and evaluated their associations with birth weight and gestational age at birth (GA) z-scores, separately, using linear regression and premature birth, small-for-gestational age (SGA), and large-for-gestational-age (LGA) using logistic regression adjusting for relevant covariates. We additionally tested interaction terms between prenatal DPs and maternal diabetes status in separate models. We adjusted for multiple comparisons using false discovery rate. Results We identified two dietary patterns: (1) solid fats, refined grains, and cheese (SRC) and (2) vegetables, oils, and fruit (VOF). Comparing highest-to-lowest quartiles, the VOF DP was significantly associated with greater birth weight (β = 0.40, 95% CIs: 0.10, 0.70; Ptrend = 0.011), GA (β = 0.32, 95% CIs: 0.03, 0.61; Ptrend = 0.036) and lower odds of premature birth (OR = 0.31, 95% CIs: 0.10, 0.95; Ptrend = 0.049) and SGA (OR = 0.18, 95% CIs: 0.06, 0.58; Ptrend= 0.028). Only among women with GDM, a 1-SD score increase in the SRC prenatal DP was significantly associated with lower birth weight (β = -0.20, 95% CIs -0.39, -0.02; Pinteraction = 0.040). Conclusions Among low-income Hispanic/Latina pregnant women, greater adherence to the VOF prenatal DP may lower the risk of premature birth and SGA. Greater adherence to the SRC DP, however, may adversely affect newborn birth weight among mothers with GDM but future research is needed to verify our findings.

Background It is well documented that persons of color experience disproportionate exposure to environmental contaminants, including air pollution, and have poorer pregnancy outcomes. This study assessed the critical windows of exposure to ambient air pollution on in utero fetal growth among structurally marginalized populations in urban Los Angeles. Methods Participants (N = 281) from the larger ongoing MADRES pregnancy cohort study were included in this analysis. Fetal growth outcomes were measured on average at 32 $$\pm$$ ± 2 weeks of gestation by a certified sonographer and included estimated fetal weight, abdominal circumference, head circumference, biparietal diameter and femur length. Daily ambient air pollutant concentrations were estimated for four pollutants (particulate matter less than 2.5 µm (PM2.5) and less than 10 µm (PM10) in aerodynamic diameter, nitrogen dioxide (NO2), and 8-h maximum ozone (O3)) at participant residences using inverse-distance squared spatial interpolation from ambient monitoring data. Weekly gestational averages were calculated from 12 weeks prior to conception to 32 weeks of gestation (44 total weeks), and their associations with growth outcomes were modeled using adjusted distributed lag models (DLMs). Results Participants were on average 29 years $$\pm$$ ± 6 old and predominately Hispanic (82%). We identified a significant sensitive window of PM2.5 exposure (per IQR increase of 6 $$\mathrm{\mu g}/\mathrm{m}$$ μ g / m 3) between gestational weeks 4–16 for lower estimated fetal weight $$\beta$$ β averaged4-16 = -8.7 g; 95% CI -16.7, -0.8). Exposure to PM2.5 during gestational weeks 1–23 was also significantly associated with smaller fetal abdominal circumference ($$\beta$$ β averaged1-23 = -0.6 mm; 95% CI -1.1, -0.2). Additionally, prenatal exposure to PM10 (per IQR increase of 13 $$\mathrm{\mu g}/\mathrm{m}$$ μ g / m 3) between weeks 6–15 of pregnancy was significantly associated with smaller fetal abdominal circumference ($$\beta$$ β averaged6-15 = -0.4 mm; 95% CI -0.8, -0.1). Discussion These results suggest that exposure to particulate matter in early to mid-pregnancy, but not preconception or late pregnancy, may have critical implications on fetal growth.