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BACKGROUND: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. OBJECTIVES: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006; Cincinnati, Ohio). METHODS: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (푛= 266) and peripheral leukocytes at 12 years of age (푛= 160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children’s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999–2002; Boston, Massachusetts) to replicate significant associations. RESULTS: After adjusting for covariates, 435 cytosine–guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, 푞< 0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children’s age. DISCUSSION: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. [ABSTRACT FROM AUTHOR]

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑ DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposure to endocrine disruptors has been associated with increased risk of childhood obesity. However, epidemiologic studies on polybrominated diphenyl ethers (PBDEs) are limited despite animal studies indicating PBDEs' potential role as an obesogen. OBJECTIVES: We investigated whether maternal concentrations of BDEs 28, 47, 99, 100, 153, and XPBDEs during pregnancy were associated with anthropometric measures in children aged 1-8 years. METHODS: We examined 318 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort enrolled from 2003 through 2006 (Cincinnati, OH). Serum PBDEs were measured at 16 ± 3 weeks gestation. We measured child height (1-8 years), weight (1-8 years), body mass index (BMI) (2-8 years), waist circumference (4-8 years), and body fat (8 years). To account for repeated measures, we used linear mixed models and generalized estimating equations to estimate associations between maternal PBDEs and child anthropometric measures. RESULTS: We found no statistically significant associations between prenatal PBDEs and height or weight z-score. A 10-fold increase in maternal serum BDE-153 was associated with lower BMI z-score (β = -0.36; 95% CI: -0.60, -0.13) at 2-8 years, smaller waist circumference (P = -1.81 cm; 95% CI: -3.13, -0.50) at 4-8 years, and lower percent body fat (β = -2.37%; 95% CI: -4.21, -0.53) at 8 years. A decrease in waist circumference at 4-8 years was observed with a 10-fold increase in BDE-100 (β = -1.50 cm; 95% CI: -2.93, -0.08) and ΣPBDEs (β = -1.57 cm; 95% CI:-3.11,-0.02). CONCLUSIONS: Reverse causality may have resulted in prenatal PBDEs, particularly BDE-153, and decreased BMI, waist circumference, and body fat. CITATION: Vuong AM, Braun JM, Sjödin A, Webster GM, Yolton K, Lanphear BP, Chen A. 2016. Prenatal polybrominated diphenyl ether exposure and body mass index in children up to 8 years of age. Environ Health Perspect 124:1891-1897; http://dx.doi.org/10.1289/EHP139 [ABSTRACT FROM AUTHOR]

Objective: To examine relationships between prenatal perfluoroalkyl substance (PFAS) exposure and adiposity in children born to women who lived downstream from a fluoropolymer manufacturing plant.Methods: Data are from a prospective cohort in Cincinnati, Ohio (HOME Study). Perfluorooctanoic (PFOA), perfluorooctane sulfonic (PFOS), perfluorononanoic (PFNA), and perfluorohexane sulfonic (PFHxS) acids were measured in prenatal serum samples. Differences were measured in body mass index z-scores (BMI), waist circumference, and body fat at 8 years of age (n = 204) and BMI between 2-8 years of age (n = 285) according to PFAS concentrations.Results: Children born to women in the top two PFOA terciles had greater adiposity at 8 years than children in the 1st tercile. For example, waist circumference (cm) was higher among children in the 2nd (4.3; 95% CI: 1.7, 6.9) and 3rd tercile (2.2; 95% CI: -0.5, 4.9) compared to children in the 1st tercile. Children in the top two PFOA terciles also had greater BMI gains from 2 to 8 years compared to children in the 1st tercile (P < 0.05). PFOS, PFNA, and PFHxS were not associated with adiposity.Conclusions: In this cohort, higher prenatal serum PFOA concentrations were associated with greater adiposity at 8 years and a more rapid increase in BMI between 2-8 years. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants. OBJECTIVES: We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera. METHODS: We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ±3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256). RESULTS: Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT4), respectively. Both congeners were also positively associated with maternal free thyroxine (FT4). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT3 and FT3). A 10-fold increase in BDE-28 was associated with elevated FT3 concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum. CONCLUSIONS: These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T4 and T3 during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Exposure to phthalates, a class of endocrine disrupting chemicals, is ubiquitous. We examined the association of urinary phthalate metabolite concentrations during pregnancy with maternal blood pressure and risk of pregnancy-induced hypertensive diseases.Methods: We used data from the Health Outcomes and Measures of the Environment Study, a prospective birth cohort of low-risk pregnant women recruited between March 2003 and January 2006. We analyzed maternal urine samples collected at 16 and 26 weeks gestation for 9 phthalate monoester metabolites reflecting exposure to 6 phthalate diesters. Outcomes included maternal blood pressure at <20 and ≥ 20 weeks gestation and pregnancy induced hypertensive diseases (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome).Results: Data were available for 369 women who gave birth to singleton, live-born infants without congenital anomalies. Of the phthalate metabolites evaluated, only mono-benzyl phthalate (MBzP) concentrations were significantly associated with maternal diastolic blood pressure at <20 weeks gestation. Women in the third MBzP tercile at 16 weeks gestation had diastolic blood pressure 2.2 (95% CI: 0.5-3.9) mm Hg higher at <20 weeks gestation and 2.8 (95% CI: 0.9-4.7) mm Hg higher at ≥ 20 weeks gestation compared to women in the first tercile. Compared to women in the first tercile, women in the top MBzP tercile at 16 weeks had an increased risk of developing pregnancy-induced hypertensive diseases (RR = 2.92, 95 % CI 1.15-7.41, p-value for trend = 0.01). MBzP concentrations at 26 weeks gestation were not as strongly associated with blood pressure at ≥ 20 weeks gestation or risk of pregnancy-induced hypertensive diseases.Conclusion: This study suggests that maternal urinary MBzP concentrations may be associated with increased diastolic blood pressure and risk of pregnancy-induced hypertensive diseases. [ABSTRACT FROM AUTHOR]

Background: Early-life exposure to bisphenol A (BPA) may increase childhood obesity risk, but few prospective epidemiological studies have investigated this relationship. Objective: We sought to determine whether early-life exposure to BPA was associated with increased body mass index (BMI) at 2–5 years of age in 297 mother–child pairs from Cincinnati, Ohio (HOME Study). Methods: Urinary BPA concentrations were measured in samples collected from pregnant women during the second and third trimesters and their children at 1 and 2 years of age. BMI z-scores were calculated from weight/height measures conducted annually from 2 through 5 years of age. We used linear mixed models to estimate BMI differences or trajectories with increasing creatinine-normalized BPA concentrations. Results: After confounder adjustment, each 10-fold increase in prenatal (β = –0.1; 95% CI: –0.5, 0.3) or early-childhood (β = –0.2; 95% CI: –0.6, 0.1) BPA concentrations was associated with a modest and nonsignificant reduction in child BMI. These inverse associations were suggestively stronger in girls than in boys [prenatal effect measure modification (EMM) p-value = 0.30, early-childhood EMM p-value = 0.05], but sex-specific associations were imprecise. Children in the highest early-childhood BPA tercile had lower BMI at 2 years (difference = –0.3; 95% CI: –0.6, 0.0) and larger increases in their BMI slope from 2 through 5 years (BMI increase per year = 0.12; 95% CI: 0.07, 0.18) than children in the lowest tercile (BMI increase per year = 0.07; 95% CI: 0.01, 0.13). All associations were attenuated without creatinine normalization. Conclusions: Prenatal and early-childhood BPA exposures were not associated with increased BMI at 2–5 years of age, but higher early-childhood BPA exposures were associated with accelerated growth during this period. [ABSTRACT FROM AUTHOR]

Background: Excess weight gain in infancy and childhood is associated with increased risk of subsequent obesity. Identifying patterns of infancy and childhood weight gain associated with subsequent obesity or overweight status could help identify children at highest risk. Thus, we examined patterns of infancy and early childhood BMI in relation to mid-childhood overweight and obesity status.Methods: In a prospective cohort of 215 children from Cincinnati, OH (born: 2003-2006), we measured weight and length or height at ages 4 weeks and 1, 2, 3, 4, 5, and 8 years. We calculated BMI z-scores using World Health Organization references. Using linear fixed effect models, we estimated mean BMI at each age and rates of change in BMI between ages 4 weeks and 5 years by children's overweight and obesity status at age 8 years, assessed with BMI z-scores or bioelectric impedance analysis (BIA).Results: Children who became overweight (BMI, n = 51 and BIA, n = 37) or obese (BMI, n = 22 and BIA, n = 29) at age 8 years had greater BMI at all ages compared to normal weightchildren. Children who were overweight had similar rates of change in BMI as children who were lean. Children who were obese had greater gains in BMI between age 4 weeks and 5 years, with the most rapid gains in the first 2 years.Conclusions: Results from this study of modest sample size, suggest that adiposity patterns in the first 5 years of life are related to subsequent childhood overweight and obesity risk. [ABSTRACT FROM AUTHOR]