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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 Achieving optimal folate status during early gestation reduces the risk of neural tube defects (NTDs). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit. Objective Here, we sought to investigate the determinants, including FA supplement dose and use, of plasma total and individual folate vitamer concentrations in the first and third trimesters of pregnancy. Methods Using data from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study, a cohort exposed to mandatory FA fortification, we measured plasma total folate and individual folate vitamer [5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), and non-methyl folates (sum of THF, 5-formylTHF, 5,10-methenyl-THF)] concentrations in the first and third trimesters (n  = 1,893). Using linear mixed models, we estimated associations between plasma folate concentrations, total daily supplemental FA intake, plasma vitamin B-12 concentrations, and multiple demographic, maternal, and reproductive factors. Results Almost 95% of MIREC study participants met or exceeded the recommended daily supplemental FA intake from supplements (≥400 μg/d), with approximately 25% consuming more than the Tolerable Upper Intake Level (>1000 μg/d). Over 99% of MIREC participants had a plasma total folate status indicative of maximal NTD risk reduction (25.5 nmol/L) regardless of FA supplement dose. UMFA was detected in almost all participants, with higher concentrations associated with higher FA doses. Determinants of adequate FA supplement intake and folate status associated with reduced NTD risk included indicators of higher socioeconomic position, higher maternal age, nulliparity, and lower prepregnancy BMI. Conclusions In the context of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to identify periods of heightened susceptibility to the effects of pre- and postnatal secondhand tobacco smoke (SHS) exposure on body composition at age 12 years.Methods: The study used data from 217 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort in Cincinnati, Ohio. Using multiple informant models, the study estimated associations of maternal serum cotinine (16 and 26 weeks of pregnancy) and child serum cotinine concentrations (at age 12, 24, 36, and 48 months) with measures of body composition obtained with anthropometry and dual-energy x-ray absorptiometry at 12 years. We examined whether there were differences between these associations for pre- and postnatal exposure periods and potential effect measure modification by sex.Results: Postnatal cotinine concentrations were associated with higher weight, BMI, body fat and lean mass, waist circumference, and visceral, android, and gynoid fat. Each 10-fold increase in postnatal cotinine was associated with 76% increased risk of overweight or obesity (95% CI: 1.13-2.75). Associations between prenatal concentrations and measures of body composition at 12 years were generally null.Conclusions: Postnatal exposure to SHS may increase adolescent adiposity and lean mass. Future studies should determine whether early-life exposures to SHS are associated with other cardiometabolic risk markers. [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: Endocrine-disrupting chemicals may alter glucose homeostasis, especially during pregnancy. Biomonitoring studies suggest ubiquitous human exposure to organophosphate esters (OPEs), chemicals with endocrine-disrupting capabilities. Few studies have examined the association between maternal exposure to OPEs and blood glucose during pregnancy.Methods: With data from 301 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA, we examined whether OPE concentrations were associated with changes in blood glucose. We quantified four OPE metabolites in maternal spot urine samples collected at 16- and 26-weeks pregnancy. We extracted results from the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) via medical chart review. Women with GCT ≥ 140 mg/dL or any abnormal values in OGTT (≥ 95 mg/dL fasting glucose, ≥ 180 mg/dL 1-h glucose, ≥ 155 mg/dL 2-h glucose, ≥ 140 mg/dL 3-h glucose) were defined as having elevated glucose levels. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of individual OPE metabolites and OPE mixtures with blood glucose levels during pregnancy. We used modified Poisson regression to estimate the associations of OPE metabolite concentrations with elevated glucose levels. We further examined effect measure modification by maternal characteristics (age, pre-pregnancy body mass index [BMI], and race/ethnicity).Results: Diphenyl phosphate (DPHP) had the highest geometric mean concentration of the urinary OPE metabolites (1.83 μg/L at 16 weeks, 1.24 μg/L at 26 weeks). Thirty women (10.0%) had elevated glucose levels. Individual OPE metabolites or their mixtures were not significantly associated with continuous GCT results. We did not observe effect measure modification by maternal age, pre-pregnancy BMI categories, or race/ethnicity. Compared with women in the 1st tertile of average DPHP of 16- and 26 weeks of pregnancy, women in the 3rd tertile tended to have a reduced risk of elevated glucose levels (RR = 0.41, 95% CI = 0.16-1.06, p for trend = 0.06).Conclusion: In this cohort, maternal urinary OPE metabolite concentrations were weakly associated with blood glucose levels during pregnancy. [ABSTRACT FROM AUTHOR]

The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1–5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies. • This cohort study examines OPEs at ages 1–5 years and cognition at age 8 years. • In child urine, BCEP was detected at 90–95%, BDCIPP at 99%, and DPHP at 99–100%. • Point estimates for OPEs and cognition were small, and 95% CIs included the null. • SES variables modified associations; disadvantaged children have worse outcomes. [ABSTRACT FROM AUTHOR]

Arsenic exposure during pregnancy may increase the risk for intellectual deficits in children, but limited data exist from prospective epidemiologic studies, particularly at low arsenic exposure levels. We investigated the association between prenatal maternal urinary arsenic concentrations and childhood cognitive abilities in the Health Outcomes and Measures of the Environment (HOME) Study. We used anion exchange chromatography coupled with inductively coupled plasma mass spectrometry detection to measure arsenic species content in pregnant women's urine. The summation of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) refers to ∑As. We assessed children's cognitive function (n = 260) longitudinally at 1-, 2-, and 3-years using Bayley Scales of Infant and Toddler Development, at 5 years using Wechsler Preschool and Primary Scale of Intelligence, and at 8 years using Wechsler Intelligence Scale for Children. We observed a modest decrease in mental development index and full-scale intelligence quotient at ages 3 and 5 years with each doubling of ∑As with estimated score (ß) differences and 95% confidence interval (CI) of -1.8 from -4.1 to 0.5 and -2.5 from -5.1 to 0.0, respectively. This trend was stronger and reached statistical significance among children whose mothers had lower iAs methylation capacity and low urinary arsenobetaine concentrations. Our findings suggest that arsenic exposure levels relevant to the general US population may affect children's cognitive abilities. [ABSTRACT FROM AUTHOR]