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Background: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals commonly used in the production of household and consumer goods. While exposure to PFAS has been associated with greater adiposity in children and adults, less is known about associations with gestational weight gain (GWG).Methods: We quantified using mass spectrometry perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS) and perfluorononanoate (PFNA) in maternal serum from 18 ± 5 weeks' gestation (mean ± standard deviation (std)) in a prospective pregnancy and birth cohort (2003-2006, Cincinnati, Ohio) (n = 277). After abstracting weight data from medical records, we calculated GWG from 16 ± 2 weeks' gestation (mean ± std) to the measured weight at the last visit or at delivery, rate of weight gain in the 2nd and 3rd trimesters (GWR), and total weight gain z-scores standardized for gestational age at delivery and pre-pregnancy BMI. We investigated covariate-adjusted associations between individual PFAS using multivariable linear regression; we assessed potential effect measure modification (EMM) by overweight/obese status (pre-pregnancy BMI<25 kg/m2 v. ≥25 kg/m2). Using weighted quantile sum regression, we assessed the combined influence of these four PFAS on GWG and GWR.Results: Each doubling in serum concentrations of PFOA, PFOS, and PFNA was associated with a small increase in GWG (range 0.5-0.8 lbs) and GWR (range 0.03-0.05 lbs/week) among all women. The association of PFNA with GWG was stronger among women with BMI≥25 kg/m2 (β = 2.6 lbs; 95% CI:-0.8, 6.0) than those with BMI<25 kg/m2 (β = -1.0 lbs; 95% CI:-3.8, 1.8; p-EMM = 0.10). We observed associations close to the null between PFAS and z-scores and between the PFAS exposure index (a combined summary measure) and the outcomes.Conclusion: Although there were consistent small increases in gestational weight gain with increasing PFOA, PFOS, and PFNA serum concentrations in this cohort, the associations were imprecise. Additional investigation of the association of PFAS with GWG in other cohorts would be informative and could consider pre-pregnancy BMI as a potential modifier. [ABSTRACT FROM AUTHOR]

Gestational exposure to chemical mixtures, which is prevalent among pregnant women, may be associated with adverse childhood neurodevelopment. However, few studies have examined relations between gestational chemical mixture exposure and children's cognitive abilities. In a cohort of 253 pregnant women and their children from Cincinnati, OH (enrolled 2003–2006), we quantified biomarker concentrations of 43 metals, phthalates, phenols, polybrominated diphenyl ethers, organophosphate and organochlorine pesticides, polychlorinated biphenyls, perfluoroalkyl substances, and environmental tobacco smoke in blood or urine. Using k-means clustering and principal component (PC) analysis, we characterized chemical mixtures among pregnant women. We assessed children's cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV at ages 5 and 8 years, respectively. We estimated covariate-adjusted differences in children's cognitive ability scores ]=cross clusters, and with increasing PC scores and individual biomarker concentrations. Geometric mean biomarker concentrations were generally highest, intermediate, and lowest among women in clusters 1, 2, and 3, respectively. Children born to women in clusters 1 and 2 had 5.1 (95% CI: 9.4,-0.8) and 2.0 (95% CI: 5.5, 1,4) lower performance IQ scores compared to children in cluster 3, respectively. PC scores and individual chemical biomarker concentrations were not associated with cognitive abilities. In this cohort, combined prenatal exposure to phenols, certain phthalates, pesticides, and perfluoroalkyl substances was inversely associated with children's cognition, but some individual chemical biomarker concentrations were not. Additional studies should determine if the aggregate impact of these chemicals on cognition is different from their individual effects. • K-means clustering and PCA used to create mixtures of chemical mixture exposure. • Chemical mixtures are inversely associated with children's cognition. • Individual chemical biomarkers in these mixtures were associated with lower IQ. [ABSTRACT FROM AUTHOR]

• We found that certain clusters and principal components were inversely associated with infant birth length. • Individual chemcial biomarkers in these clusters or PCs were associated with lower birth length. • Cluster, PCs, and individual biomarker were not associated with other birth outcomes. • The consistency of these metrics suggests that these results are not method dependent. Exposure to mixtures of environmental chemicals are prevalent among pregnant women and may be associated with altered fetal growth and gestational age. To date, most research regarding environmental chemicals and neonatal outcomes has focused on the effect of individual agents. In a prospective cohort of 380 pregnant women from Cincinnati, OH (enrolled 2003–2006), we used biomarkers to estimate exposure to 43 phenols, phthalates, metals, organophosphate/pyrethroid/organochlorine pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, perfluoroalkyl substances (PFAS), and environmental tobacco smoke. Using three approaches, we estimated covariate-adjusted associations of chemical mixtures or individual chemicals with gestational-age-specific birth weight z-scores, birth length, head circumference, and gestational age: k-means clustering, principal components (PC), and one-chemical-at-a-time regression. We identified three chemical mixture profiles using k-means clustering. Women in cluster 1 had higher concentrations of most phenols, three phthalate metabolites, several metals, organophosphate/organochlorine pesticides, polychlorinated biphenyls, and several PFAS than women in clusters 2 and 3. On average, infants born to women in clusters 1 (−1.2 cm; 95% CI: −1.9, −0.5) and 2 (−0.5 cm; 95% CI: −1.1, 0.1) had lower birth length than infants in cluster 3. Six PCs explained 50% of the variance in biomarker concentrations and biomarkers with similar chemical structures or from shared commercial/industrial settings loaded onto commons PCs. Each standard deviation increase in PC 1 (organochlorine pesticides, some phenols) and PC 6 (cadmium, bisphenol A) was associated with 0.2 cm (95% CI: −0.4, 0.0) and 0.1 cm (95% CI: −0.4, 0.1) lower birth length, respectively. Organochlorine compounds, parabens, and cadmium were inversely associated with birth length in the one-chemical-at-a-time analysis. Cluster membership, PC scores, and individual chemicals were not associated with other birth outcomes. All three methods of characterizing multiple chemical exposures in this cohort identified inverse associations of select organochlorine compounds, phenols, and cadmium with birth length, but not other neonatal outcomes. [ABSTRACT FROM AUTHOR]