Prenatal environmental exposures may influence fetal growth by disrupting the maternal metabolome and placental function. This exploratory study integrates untargeted maternal serum metabolomics and placental transcriptomics to identify shared molecular pathways through which the maternal environment affects fetal development. Data were drawn from the SAWASDEE birth cohort in northern Thailand, comprising pregnant farmworkers living in an agricultural region with known environmental exposure concerns. Weighted gene coexpression network analysis (WGCNA) of placental transcriptomic data (n = 254) identified gene expression modules, which were analyzed for associations with neonatal outcomes in a subset with paired maternal metabolomics and birth data (n = 40). A placental gene module enriched for myogenesis-related genes was inversely associated with birth weight (β = −0.11, p = 0.03). Seventeen maternal serum metabolic features were associated with both this module and birth weight, including phospholipids related to membrane remodeling and putatively annotated quinoline-containing xenobiotic-like features with structural similarity to combustion-related or industrial compounds. Mediation analysis did not identify statistically significant indirect effects, although one putative xenobiotic-like feature showed a directionally consistent estimate. In this exploratory analysis, these findings identify maternal metabolomic patterns and placental gene networks that are associated with fetal growth and generate hypotheses regarding biologically relevant pathways linking maternal metabolism, placental function, and neonatal growth. Multiomics integration provides a useful exploratory framework for identifying candidate molecular pathways that warrant validation in larger studies.
Ye-Wei Wang, Dong-Hai Liang, Duan Wang et al.· Environment & Health· 0 citations
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with small-for-gestational age (SGA), an adverse pregnancy outcome indicative of intrauterine growth restriction (IUGR). Evidence from previous environmental epidemiologic work suggests that lipids contribute to this association through oxidative stress and inflammation. Therefore, we conducted an exploratory study by analyzing the maternal lipidome with the meet-in-the-middle approach to identify potential intermediates. In the Atlanta African American Maternal–Child Cohort, pregnant participants provided serum samples between 6 and 17 weeks gestation, which underwent targeted PFAS analysis (N: total = 513, SGA = 61) and untargeted lipidomics analysis (N: total = 330, SGA = 36). A lipidome-wide association study (LWAS) was conducted for PFNA, PFOA, PFOS, and PFHxS with multivariable regression and their mixture with quantile g-computation. A separate LWAS was performed for SGA with multivariable regression. Lipid pathway analysis was performed in LIPEA (Lipid Pathway Enrichment Analysis). Lipidomic signatures that overlapped between any PFAS LWAS and the SGA LWAS were considered intermediates. A simultaneous, 1-quartile increase in serum concentrations of PFNA, PFOA, PFOS, and PFHxS at early pregnancy was associated with a 43% increase in delivery of an SGA newborn (Odds Ratio = 1.43; 95% Confidence Interval = 1.02, 2.00). The overall mixture effect was driven by PFNA (weight = 0.42). There were 321 features associated with the PFAS mixture and 25 features associated with SGA in the maternal lipidome (all p < 0.05, but none remained significant after false discovery rate correction). After confirmation and annotation, three intermediate metabolites were identified, including phosphatidylinositol 18:1–20:4, phosphatidylcholine 32:0, and monoacylglycerol 18:0. The pathways for glycerophospholipid metabolism, retrograde endocannabinoid signaling, insulin resistance, and long-term depression were also enriched in the LWAS for PFNA, PFOA, PFOS, PFHxS, the PFAS mixture, and SGA. Global analysis of the maternal lipidome during early pregnancy revealed diverse bioactive lipid involvement in the PFAS-SGA association. Additional research is warranted to understand if antioxidants and anti-inflammatory nutrients would attenuate exposure effects on adverse maternal–child health outcomes.
K. Taibl, Anne L. Dunlop, Paula-Dene C. Nesbeth et al.· Environmental Health Perspec...· 0 citations
BackgroundExposure to per- and polyfluoroalkyl substances (PFAS) is linked to reduced fetal growth, yet little is known about potentially modifiable factors that may mitigate these harmful effects.AimIn this study, we assessed whether prenatal dietary factors, including folate, vitamin D, and dietary inflammation, may modify the inverse associations between prenatal PFAS exposure and birthweight for gestational age z-scores (BWZ).MethodsParticipants were a subset of the prospective Atlanta African American Maternal-Child Cohort (N = 268, delivery dates between 2014 and 2018), which includes serum and dietary intake data. Serum collected at 8-14 weeks' gestation was analyzed for four PFAS (perfluorohexane sulfonic acid, perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid) and total and free 25-hydroxyvitamin D (25(OH)D). A semi-quantitative food frequency questionnaire administered during early pregnancy was used to ascertain dietary folate equivalents (DFE) and dietary inflammatory index (DII) over the last three months. We used linear regression stratified by dichotomized dietary measures (DFE, total and free 25(OH)D, and DII) to assess effect modification of the association between individual PFAS and BWZ. Mixture effects were estimated using quantile-based g-computation and Bayesian kernel machine regression.SummaryA natural log increase in PFOS and PFOA was more strongly associated with lower BWZ only among participants with pro-inflammatory diets (DII ≥75th percentile) or low 25(OH)D (total 25(OH)D < 75th percentile). Similar patterns were observed in PFAS mixture analyses (e.g. ΨDII≥75thpercentile = -0.47, 95% CI = -0.77, -0.18, and ΨDII<75thpercentile = -0.08, 95% CI = -0.24, 0.07). Overall, maternal dietary factors may influence susceptibility to PFAS-related fetal growth effects.
Yun-Jie Huang, Dong-Hai Liang, Anne L. Dunlop et al.· Nutrition and Health· 0 citations
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