Introduction: Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11/2001. Evidence suggests that PFAS may have cardiometabolic effects, including alterations in lipid profiles. This study evaluated the association between cord blood PFAS and lipids in a population prenatally exposed to the WTC disaster. Study Population: 222 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at hospitals located near the WTC site: Beth Israel, St. Vincent’s, and New York University Downtown. Methods: We evaluated the association between 5 cord blood PFAS—perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecane sulfonate (PFDS)—and cord blood lipids (total lipids, total cholesterol, triglycerides). Results: Median (interquartile range [IQR]) concentrations of PFAS were 6.32 (4.58–8.57), 2.46 (1.77–3.24), 0.38 (0.25–0.74), 0.66 (0.48–0.95) and 0.11 (0.09–0.16) ng/mL for PFOS, PFOA, PFNA, PFHxS, and PFDS, respectively. Median (IQR) for lipids were 59.0 (51.5–68.5) mg/dL for total cholesterol, 196.5 (170.5–221.2) mg/dL for total lipids and 33.1 (24.2–43.9) mg/dL for triglycerides. In fully adjusted models, several PFAS were associated with higher lipid levels, including evidence of a strong linear trend between triglycerides and both PFOA and PFHxS. Conclusions: Findings support previous evidence of an association between PFAS exposure and altered lipid profiles and add novel information on this relationship in cord blood, as well as for an understudied PFAS, PFDS (J Clin Endocrinol Metab 105: 43–54, 2020).

Inorganic arsenic exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes; however, this profile has also been associated with increased risk for diabetes-related outcomes. The mechanism behind these contrasting associations is equivocal; we hypothesized one carbon metabolism (OCM) may play a role. We evaluated the association between OCM-related variables (nutrient intake and genetic variants) and both arsenic metabolism biomarkers (iAs%, MMA% and DMA%) and diabetes-related outcomes (metabolic syndrome, diabetes, HOMA2-IR and waist circumference) in 935 participants free of prevalent diabetes and metabolic syndrome from the Strong Heart Family Study, a family-based prospective cohort comprised of American Indian tribal members aged 14+ years. Of the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3 years of follow-up and of the 1458 participants free of diabetes at baseline, 167 (11.3%) developed diabetes over follow-up. OCM nutrients were not associated with arsenic metabolism, however, higher vitamin B6 was associated with diabetes-related outcomes (higher HOMA2-IR and increased risk for diabetes and metabolic syndrome). A polymorphism in an OCM-related gene, methionine synthase (MTR), was associated with both higher MMA% (β = 2.57, 95% CI: 0.22, 4.92) and lower HOMA2-IR (GMR = 0.79, 95% CI = 0.66, 0.93 per 5 years of follow-up). Adjustment for OCM variables did not affect previously reported associations between arsenic metabolism and diabetes-related outcomes; however, the association between the MTR variant and diabetes-related outcomes were attenuated after adjustment for arsenic metabolism. Our findings suggest MMA% may be a partial mediator in the association between OCM and diabetes-related outcomes. Additional mediation analyses with longer follow-up period are needed to confirm this finding. Further research is needed to determine whether excess B vitamin intake is associated with increased risk for diabetes-related outcomes.