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BACKGROUND: Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. OBJECTIVES: We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) z-scores and risk of overweight/ obesity in eight U.S. cohorts. METHODS: We used data from 1,391 mother–child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999–2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI 풵-scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI 풵-scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. RESULTS: We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI 풵-scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI 풵-scores (β=0.07; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [relative risk (RR)=1.10; 95% CI: 1.04, 1.16] and 푁-methyl perfluorooctane sulfonamido acetic acid (RR=1.06; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose–response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. DISCUSSION: In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI 풵-score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. [ABSTRACT FROM AUTHOR]

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: Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional. OBJECTIVES: We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y. METHODS: Among 206 mother–child pairs enrolled in a prospective cohort (2003–2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) 푧-scores for six skeletal sites. We estimated covariate-adjusted 푧-score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child's sex or mediated by whole-body lean mass. RESULTS: In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC 푧-scores in children. Differences in forearm BMC 푧-scores were -0.17 [95% confidence interval (CI): -0.35, 0.01] and -0.24 (95% CI: -0.44, -0.05) per doubling of PFOA and PFNA, respectively, and -0.18 (95% CI: -0.34, -0.02) per quartile increase in the PFAS mixture. Child's sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD z-score per doubling were -0.31 (95% CI: -0.58, -0.03) among males and 0.07 (95% CI: -0.16, 0.30) among females (modification 푝= 0.04). Except for PFNA among females, these associations were not mediated by whole-body lean mass. DISCUSSION: Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence [ABSTRACT FROM AUTHOR]

Autism spectrum disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1%–2% of children. Although prenatal exposure to toxicants has been associated with autistic behaviors, most studies have been focused on shifts in mean behavior scores. We used Bayesian quantile regression to assess the associations between log2-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal–Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008–2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Using the Social Responsiveness Scale (SRS), in which higher scores denote more autistic-like behaviors, autistic behaviors were assessed in 478 children aged 3–4 years old. Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends in which associations increased in magnitude from the bottom to the top of the SRS distribution. These results suggest that quantile regression can reveal nuanced relationships and, thus, should be more widely used by epidemiologists. [ABSTRACT FROM AUTHOR]

We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; ß = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown OBJECTIVES: Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth METHODS: The present study included 845 pregnant women from Wuhan, China (2013–2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile. RESULTS: Medians (25th–75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19–3.85), 0.65 (0.34–1.39), and 0.38 (0.13– 1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p-values (p,trend < 0.05) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome. CONCLUSIONS: Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men's exposure is understudied. OBJECTIVES: We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. METHODS: In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004-2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. RESULTS: Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83%, p-value<0:01) and deodorant (74%, p-value<0:01). In contrast, the largest percent increase for parabens was associated with the use of suntan/sunblock lotion (66-156%) and hand/body lotion (79-147%). Increases in MEP and parabens were generally greater with PCP use within 6 h of urine collection. A subset of 10 PCPs that were used within 6 h of urine collection contributed to at least 70% of the weighted score and predicted a 254-1,333% increase in MEP and parabens concentrations. Associations between PCP use and concentrations of the other phthalate metabolites were not statistically significant. CONCLUSIONS: We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal bisphenol A (BPA) exposure has been associated with adverse neurodevelopment in epidemiological studies. However, prior studies had limited statistical power to examine sex-specific effects, and few examined child cognition. OBJECTIVES: We estimated the association between prenatal BPA exposure and child neurobehavior at 3 y of age in a prospective cohort of 812 mothers and their children. METHODS: We measured BPA concentration in urine samples collected at ∼12 wk gestation among women enrolled in a 10-city Canadian cohort study. At approximately 3 y of age, we assessed children's cognitive abilities with the Wechsler Primary and Preschool Scale of Intelligence™-III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale™-2 (SRS-2). We estimated covariate-adjusted differences in neurobehavioral outcomes with a doubling in BPA concentration and sex-specific associations. RESULTS: BPA was not associated with WPPSI-III scores; child sex did not modify these associations. The association between BPA and BRIEF-P scores was modified by child sex (BPA×sex p-values≤0.03). For example, a doubling of BPA concentration was associated with 1-point (95% CI: 0.3, 1.7) poorer working memory in boys and 0.5-point (95% CI: -1.1, 0.1) better scores in girls. BPA was not associated with most BASC-2 scales; however, it was associated with more internalizing and somatizing behaviors in boys, but not in girls (BPA×sexp-values≤0.08). A doubling of BPA concentration was associated with poorer SRS-2 scores [β=0.3 ( 95% CI: 0, 0.7)]; this association was not modified by sex. CONCLUSION: Prenatal urinary BPA concentration was associated with some aspects of child behavior in this cohort, and some associations were stronger among boys. [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]

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: 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]