BACKGROUND
Aromatic amines (AAs) have rarely been studied in the context of pregnancy despite their ubiquity and known toxicity. To our knowledge, no study has investigated the relationship between AAs and F2-isoprostanes, which are linked to adverse maternal and child health outcomes.
METHODS
Our analytic sample included 176 participants from the Chemicals in Our Bodies prospective birth cohort. Thirty-six AAs and four F2-isoprostanes (biomarkers of oxidative stress) were measured in mid-pregnancy urine. We focused on six AAs that were detected in at least 50% of participants and calculated their molar sum (ΣAA). An additional six AAs that were detected in 20-49% of participants were analyzed as binary variables. Generalized additive mixed models were used to assess non-linearity, and linear regression models were used to examine associations between individual AAs and individual oxidative stress biomarkers, adjusting for confounders.
RESULTS
Most AAs were associated with significant increases in oxidative stress biomarkers. Increasing concentrations of ΣAA were significantly associated with 8-iso-PGF2α (β=0.25, 95% confidence interval [CI]=0.1, 0.41) and PGF2α (β=0.21, CI=0.04, 0.39). Additionally, the individual AAs o/m-toluidine and 4-chloroaniline were associated with significant increases in 8-iso-PGF2α and PGF2α.
CONCLUSIONS
Our study is the first to investigate the relationship between AAs and F2-isoprostanes during pregnancy. This study found that several AAs are associated with higher levels of oxidative stress, highlighting one potential mechanism linking AAs to adverse maternal-child health outcomes.
Madeline Chandler, T. Woodruff, R. Morello-Frosch et al.· Environmental Research· 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
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