Gestational exposure to organochlorine compounds and metals and infant birth weight: effect modification by maternal hardships.

BACKGROUND: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation. RESULTS: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (ß = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (ß = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (ß = 23 g; 95% CI: -25, 71) compared to those with higher educational status (ß = -9 g; 95% CI: -24, 6). CONCLUSIONS: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight.

Time-varying associations of gestational and childhood triclosan with pubertal and adrenarchal outcomes in early adolescence.

Background: Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage. Methods: We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003-2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]-dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males-testosterone; females-estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche. Results: For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (-29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: -18%, -2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1-3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months. Conclusion: Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan.

Early life exposure to secondhand tobacco smoke and eating behaviors at age 12 years.

BACKGROUND: Prenatal or early childhood secondhand tobacco smoke (SHS) exposure increases obesity risk. However, the potential mechanisms underlying this association are unclear, but obesogenic eating behaviors are one pathway that components of SHS could perturb. Our aim was to assess associations of prenatal and early childhood SHS exposure with adolescent eating behaviors. METHODS: Data came from a prospective pregnancy and birth cohort (N = 207, Cincinnati, OH). With multiple informant models, we estimated associations of prenatal (mean of 16 and 26 weeks of gestation maternal serum cotinine concentrations) and early childhood cotinine (average concentration across ages 12, 24, 36, and 48 months) with eating behaviors at age 12 years (Child Eating Behaviors Questionnaire). We tested whether associations differed by exposure periods and adolescent's sex. Models adjusted for maternal and child covariates. RESULTS: We found no statistically significant associations between cotinine measures and adolescent's eating behaviors. Yet, in females, prenatal cotinine was associated with greater food responsiveness (ß: 0.23; 95% CI: 0.08, 0.38) and lower satiety responsiveness (ß: -0.14; 95% CI: -0.26, -0.02); in males, prenatal and postnatal cotinine was related to lower food responsiveness (prenatal: ß: -0.25; 95% CI: -0.04, -0.06; postnatal: ß: -0.36; 95% CI: -0.06, -0.11). No significant effect modification by sex or exposure window was found for other eating behaviors. CONCLUSION: Prenatal and early childhood SHS exposures were not related to adolescent's eating behavior in this cohort; however, biological sex may modify these associations.

Per- and polyfluoroalkyl substances and bone mineral content in early adolescence: Modification by diet and physical activity.

BACKGROUND: Per- and polyfluoroalkyl substance (PFAS) exposures may negatively impact bone mineral accrual, but little is known about potential mitigators of this relation. We assessed whether associations of PFAS and their mixture with bone mineral content (BMC) in adolescence were modified by diet and physical activity. METHODS: We included 197 adolescents enrolled in a prospective pregnancy and birth cohort in Cincinnati, Ohio (2003-2006). At age 12 years, we collected serum for PFAS measurements and used dual-energy x-ray absorptiometry to measure BMC. We calculated dietary calcium intake and Health Eating Index (HEI) scores from repeated 24-h dietary recalls, physical activity scores using the Physical Activity Questionnaire for Older Children (PAQ-C), and average moderate to vigorous physical activity (MVPA) based on accelerometry. We estimated covariate-adjusted differences in BMC z-scores per interquartile range (IQR) increase of individual PFAS concentrations using linear regression and per simultaneous IQR increase in all four PFAS using g-computation. We evaluated effect measure modification (EMM) using interaction terms between each modifier and PFAS. RESULTS: Higher serum perfluorooctanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid concentrations and the PFAS mixture were associated with lower BMC z-scores. An IQR increase in all PFAS was associated with a 0.27 (-0.54, 0.01) lower distal radius BMC z-score. Associations with lower BMC were generally stronger among adolescents classified as < median for calcium intake, HEI scores, or MVPA compared to those ≥ median. The difference in distal radius BMC z-score per IQR increase in all PFAS was -0.38 (-0.72, -0.04) for those with

Gestational PBDE concentrations, persistent externalizing, and emerging internalizing behaviors in adolescents: The HOME study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. METHODS: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑5BDE: 28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log10-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. RESULTS: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑5BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑5BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑5BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑5BDE). DISCUSSION: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

Gestational thyroid hormones and autism-related traits in the EARLI and HOME studies.

Thyroid hormones are essential for neurodevelopment. Few studies have considered associations with quantitatively measured autism spectrum disorder (ASD)-related traits, which may help elucidate associations for a broader population. Participants were drawn from two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI), enrolling pregnant women who already had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study, following pregnant women from the greater Cincinnati, OH area. Gestational thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured in mid-pregnancy 16 (±3) weeks gestation serum samples. ASD-related traits were measured using the Social Responsiveness Scale (SRS) at ages 3-8 years. The association was examined using quantile regression, adjusting for maternal and sociodemographic factors. 278 participants (132 from EARLI, 146 from HOME) were included. TSH distributions were similar across cohorts, while FT4 levels were higher in EARLI compared to HOME. In pooled analyses, particularly for those in the highest SRS quantile (95th percentile), higher FT4 levels were associated with increasing SRS scores (ß = 5.21, 95% CI = 0.93, 9.48), and higher TSH levels were associated with decreasing SRS scores (ß = -6.94, 95% CI = -11.04, -2.83). The association between TSH and SRS remained significant in HOME for the 95% percentile of SRS scores (ß = -6.48, 95% CI = -12.16, -0.80), but not EARLI. Results for FT4 were attenuated when examined in the individual cohorts. Our results add to evidence that gestational thyroid hormones may be associated with ASD-related outcomes by suggesting that relationships may differ across the distribution of ASD-related traits and by familial likelihood of ASD.

Estimating effects of longitudinal and cumulative exposure to PFAS mixtures on early adolescent body composition.

Few methods have been used to characterize repeatedly measured biomarkers of chemical mixtures. We applied latent profile analysis (LPA) to serum concentrations of 4 perfluoroalkyl and polyfluoroalkyl substances (PFAS) measured at 4 time points from gestation to age 12 years. We evaluated the relationships between profiles and z scores of height, body mass index, fat mass index, and lean body mass index at age 12 years (n = 218). We compared LPA findings with an alternative approach for cumulative PFAS mixtures using g-computation to estimate the effect of simultaneously increasing the area under the receiver operating characteristic curve (AUC) for all PFAS. We identified 2 profiles: a higher PFAS profile (35% of sample) and a lower PFAS profile (relative to each other), based on their average PFAS concentrations at all time points. The higher PFAS profile had generally lower z scores for all outcomes, with somewhat larger effects for males, though all 95% CIs crossed the null. For example, the higher PFAS profile was associated with a 0.50-unit lower (ß = -0.50; 95% CI, -1.07 to 0.08) BMI z score among males but not among females (ß = 0.04; 95% CI, -0.45 to 0.54). We observed similar patterns with AUCs. We found that a higher childhood PFAS profile and higher cumulative PFAS mixtures may be associated with altered growth in early adolescence. This article is part of a Special Collection on Environmental Epidemiology.

Evaluating the association between longitudinal exposure to a PFAS mixture and adolescent cardiometabolic risk in the HOME Study.

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) throughout gestation and childhood may impact cardiometabolic risk. Methods: In 179 HOME Study participants (Cincinnati, OH; recruited 2003-2006), we used latent profile analysis to identify two distinct patterns of PFAS exposure from serum concentrations of four PFAS measured at birth and ages 3, 8, and 12 years. We assessed the homeostatic model of insulin resistance, triglycerides-to-high-density lipoprotein cholesterol ratio, leptin-to-adiponectin ratio, systolic blood pressure, visceral fat, and hemoglobin A1c levels at age 12 years. We used multivariable linear regression to assess the association of membership in the longitudinal PFAS mixture exposure group with a summary measure of overall cardiometabolic risk and individual components. Results: One PFAS exposure profile (n = 66, 39%) had higher geometric means of all PFAS across all visits than the other. Although adjusted associations were null in the full sample, child sex modified the association of longitudinal PFAS mixture exposure group with overall cardiometabolic risk, leptin-to-adiponectin ratio, systolic blood pressure, and visceral fat (interaction term P values: 0.02-0.08). Females in the higher exposure group had higher cardiometabolic risk scores (ß = 0.43; 95% CI = -0.08, 0.94), systolic blood pressures (ß = 0.6; 95% CI = 0.1, 1.1), and visceral fat (ß = 0.44; 95% CI = -0.13, 1.01); males had lower cardiometabolic risk scores (ß = -0.52; 95% CI = -1.06, -0.06), leptin-to-adiponectin ratios (ß = -0.7; 95% CI = -1.29, -0.1), systolic blood pressures (ß = -0.14; 95% CI = -0.7, 0.41), and visceral fat (ß = -0.52; 95% CI = -0.84, -0.19). Conclusions: Exposure to this PFAS mixture throughout childhood may have sex-specific effects on adolescent cardiometabolic risk.

Evaluating Mixtures of Urinary Phthalate Metabolites and Serum Per-/Polyfluoroalkyl Substances in Relation to Adolescent Hair Cortisol: The HOME Study.

Results of toxicological studies indicate that phthalates and per-/polyfluoroalkyl substances (PFAS), 2 classes of endocrine-disrupting chemicals, may alter the functioning of the hypothalamic-pituitary-adrenocortical (HPA) axis. We evaluated the associations of urinary phthalate metabolites and serum PFAS during gestation and childhood with adolescent hair cortisol concentrations (pg/mg hair) at age 12 years, an integrative marker of HPA axis activity (n = 205 mother-child pairs; Cincinnati, Ohio; enrolled 2003-2006). We used quantile-based g-computation to estimate associations between mixtures of urinary phthalate metabolites or serum PFAS and hair cortisol. We also examined whether associations of individual phthalate metabolites or PFAS with cortisol varied by the timing of exposure. We found that a 1-quartile increase in all childhood phthalate metabolites was associated with 35% higher adolescent hair cortisol (phthalate mixture ψ = 0.13; 95% confidence interval: 0.03, 0.22); these associations were driven by monoethyl phthalate, monoisobutyl phthalate, and monobenzyl phthalate. We did not find evidence that phthalate metabolites during gestation or serum PFAS mixtures were related to adolescent hair cortisol concentrations. We found suggestive evidence that higher childhood concentrations of individual PFAS were related to higher and lower adolescent hair cortisol concentrations. Our results suggest that phthalate exposure during childhood may contribute to higher levels of chronic HPA axis activity.

Associations of a Prenatal Serum Per- and Polyfluoroalkyl Substance Mixture with the Cord Serum Metabolome in the HOME Study.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous and persistent chemicals associated with multiple adverse health outcomes; however, the biological pathways affected by these chemicals are unknown. To address this knowledge gap, we used data from 264 mother-infant dyads in the Health Outcomes and Measures of the Environment (HOME) Study and employed quantile-based g-computation to estimate covariate-adjusted associations between a prenatal (∼16 weeks' gestation) serum PFAS mixture [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] and 14,402 features measured in cord serum. The PFAS mixture was associated with four features: PFOS, PFHxS, a putatively identified metabolite (3-monoiodo-l-thyronine 4-O-sulfate), and an unidentified feature (590.0020 m/z and 441.4 s retention time; false discovery rate <0.20). Using pathway enrichment analysis coupled with quantile-based g-computation, the PFAS mixture was associated with 49 metabolic pathways, most notably amino acid, carbohydrate, lipid and cofactor and vitamin metabolism, as well as glycan biosynthesis and metabolism (P(Gamma) <0.05). Future studies should assess if these pathways mediate associations of prenatal PFAS exposure with infant or child health outcomes, such as birthweight or vaccine response.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Patterns of urinary organophosphate ester metabolite trajectories in children: the HOME Study.

BACKGROUND: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure. OBJECTIVE: We aimed to examine the exposure pattern of urinary OPE metabolites in children. METHODS: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. RESULTS: Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. SIGNIFICANCE: The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. IMPACT STATEMENT: In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood.

Environmental predictors of children's executive functioning development.

Executive functioning (EF) abilities develop through childhood, but this development can be impacted by various psychosocial environmental influences. Using longitudinal data from the Health Outcome and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort study, we examined if psychosocial environmental factors were significant predictors of EF development. Study participants comprised 271 children and their primary caregivers (98.5% mothers) followed from birth to age 12. We identified four distinct EF developmental trajectory groups comprising a consistently impaired group (13.3%), a descending impairment group (27.7%), an ascending impairment group (9.95%), and a consistently not impaired group (49.1%). Higher levels of maternal ADHD and relational frustration appear to be risk factors for increased EF difficulty over time, while higher family income may serve as a protective factor delaying predisposed EF impairment. Important intervention targets might include teaching positive and effective parenting strategies to mothers whose children are at risk for EF dysfunction.

Early childhood sleep quantity, but not caregiver-reported sleep problems, predicts impulse control in children at age 8 years.

Short duration of sleep and poor sleep quality have been linked to poor attention and impulse control in children. We aimed to determine the longitudinal predictive value of sleep quantity and quality during early childhood on objective and caregiver-report measures of attention, impulse control, and executive function in children at age 8 years. We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a pregnancy and birth cohort. Caregivers reported on their child's sleep at ages 2, 2.5, 3, 4, and 5 years. Analysis included 410 participants. We used longitudinal growth curve models of early childhood sleep patterns to predict neurobehavioral functioning at age 8 years. Sleep problems did not predict any of our outcome measures at age 8 years. Sleep duration trended shorter as children matured, so predictive models examined both intercept and slope. Children with the least decline in sleep duration across early childhood had fewer impulsive errors at age 8 years on a continuous performance test (unadjusted p = .013; adjusted p = .013). Children with shorter duration of sleep across early childhood had worse caregiver-reported behavioral regulation at age 8 years (unadjusted p = .002; adjusted p = .043). Neither sleep duration slope nor intercept predicted inattention or metacognitive skills at age 8 years (p > .05). Total sleep time across early childhood predicts behavior regulation difficulties in school-aged children. Inadequate sleep during early childhood may be a marker for, or contribute to, poor development of a child's self-regulatory skills.

Urinary Glyphosate Concentrations among Pregnant Participants in a Randomized, Crossover Trial of Organic and Conventional Diets.

BACKGROUND: Consumption of an organic diet reduces exposure to a range of agricultural pesticides. Only three studies have examined the effect of an organic diet intervention on exposure to the herbicide glyphosate, the most heavily used agricultural chemical in the world. Despite its widespread use, the primary sources of glyphosate exposure in humans are poorly understood. OBJECTIVE: Our objective was to examine the effect of an organic diet intervention on urinary glyphosate concentrations among pregnant individuals. METHODS: We conducted a 2-wk randomized crossover trial in which 39 pregnant participants living near (≤0.5km) and far (>0.5km) from agricultural fields received a 1-wk supply of conventional groceries and 1 wk of organic groceries, randomized to order. We collected daily first morning void urine samples and analyzed composite samples from each week for glyphosate. We examined differences in urinary glyphosate concentrations between the conventional week and the organic week among all participants and stratified by residential proximity to an agricultural field. RESULTS: Median specific gravity-adjusted glyphosate concentrations were 0.19µg/L and 0.16µg/L during the conventional and organic weeks, respectively. We observed modest decreases in urinary glyphosate concentrations from the conventional to organic week among far-field participants, but no difference among near-field participants. In secondary analyses excluding participants who did not meet a priori criteria of compliance with the intervention, we observed significant decreases in urinary glyphosate concentrations, particularly among far-field participants (p<0.01-0.02, depending on exclusion criteria). DISCUSSION: This trial is the first to examine the effect of an organic diet intervention on glyphosate among people living near and far from agricultural fields. Our results suggest that diet is an important contributor to glyphosate exposure in people living >0.5km from agricultural fields; for people living near crops, agriculture may be a dominant exposure source during the pesticide spray season. https://doi.org/10.1289/EHP12155.

Associations of prenatal and postnatal exposure to perfluoroalkyl substances with pubertal development and reproductive hormones in females and males: The HOME study.

BACKGROUND: Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce. OBJECTIVES: We examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years. METHODS: We studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003-2006). We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and females) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture. RESULTS: In females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adolescent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males. CONCLUSIONS: We observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

Dietary per- and polyfluoroalkyl substance (PFAS) exposure in adolescents: The HOME study.

BACKGROUND: Diet is the primary exposure pathway for per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations. Few studies have examined associations of dietary quality and macronutrient intake with PFAS exposure among US adolescents. OBJECTIVE: To assess relationships of self-reported dietary quality and macronutrient intake with serum PFAS concentrations in adolescents. METHODS: We used cross-sectional data from 193 Cincinnati, Ohio area adolescents (median age 12.3 years) collected from 2016 to 2019. Using 24-h food recalls completed by adolescents on three separate days, we derived Healthy Eating Index (HEI) scores, HEI components, and macronutrient intake. We measured perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations in fasting serum samples. Using linear regression, we estimated covariate-adjusted associations between dietary variables and serum PFAS concentrations. RESULTS: The median HEI score was 44 and median serum PFOA, PFOS, PFHxS, and PFNA concentrations were 1.3, 2.4, 0.7, and 0.3 ng/mL respectively. In adjusted models, higher total HEI scores, whole fruit and total fruit HEI component scores, and total dietary fiber intake were associated with lower concentrations of all four PFAS. For example, serum PFOA concentrations were 7% lower (95% CI: -15, 2) per standard deviation increase in total HEI score and 9% lower (95% CI: -18, 1) per standard deviation increase in dietary fiber. SIGNIFICANCE: Given adverse health effects associated with PFAS exposure, it is crucial to understand modifiable exposure pathways. Findings from this study may inform future policy decisions aiming to limit human exposure to PFAS.

Who benefits most from a prenatal HEPA filter air cleaner intervention on childhood cognitive development? The UGAAR randomized controlled trial.

BACKGROUND: Air pollution exposure during pregnancy affects children's brain function. Maternal stress and nutrition, socioeconomic status, and the child's sex may modify this relationship. OBJECTIVE: To identify characteristics of children with the largest increases in full-scale IQ (FSIQ) after their mothers used HEPA filter air cleaners during pregnancy. METHODS: In this randomized controlled trial we randomly assigned women to receive 1-2 air cleaners or no air cleaners during pregnancy. We analyzed maternal hair samples for cortisol and dehydroepiandrosterone (DHEA). When the children were 48 months old, we measured FSIQ with the Wechsler Preschool and Primary Scale of Intelligence. We evaluated ten potential modifiers of the intervention-FSIQ relationship using interaction terms in separate regression models. To account for correlations between modifiers, we also used a single regression model containing main effects and intervention x modifier terms for all potential modifiers. RESULTS: Among 242 mother-child dyads with complete data, the intervention was associated with a 2.3-point increase (95% CI: -1.5, 6.0 points) in mean FSIQ. The intervention improved mean FSIQ among children of mothers in the bottom (5.4 points; 95% CI: -0.8, 11.5) and top (6.1 points; 95% CI: 0.5, 11.8) cortisol tertiles, but not among those whose mothers were in the middle tertile. The largest between-group difference in the intervention's effect was a 7.5-point (95% CI: -0.7, 15.7) larger increase in mean FSIQ among children whose mothers did not take vitamins than among children whose mothers did take vitamins (interaction p-value = 0.07). We also observed larger benefits among children whose mothers did not complete university, and those with lower hair DHEA concentrations, hair cortisol concentrations outside the middle tertile, or more perceived stress. CONCLUSION: The benefits of reducing air pollution during pregnancy on brain development may be greatest for children whose mothers who do not take vitamins, experience more stress, or have less education.

Air pollution exposure and social responsiveness in childhood: The cincinnati combined childhood cohorts.

Autism Spectrum Disorder (ASD) affects about 1 in 44 children and environmental exposures may contribute to disease onset. Air pollution has been associated with adverse neurobehavioral outcomes, yet little research has examined its association with autistic-like behaviors. Therefore, our objective was to examine the association between exposure to air pollution, including NO2 and PM2.5, during pregnancy and the first year of life to ASD-like behaviors during childhood. Participants (n = 435) enrolled in the Cincinnati Childhood Allergy and Air Pollution Study and the Health Outcomes and Measures of the Environment Study were included in the analysis. Daily exposures to NO2 and PM2.5 at the residential addresses of participants were estimated using validated spatiotemporal models and averaged to obtain prenatal and first year exposure estimates. ASD-like behaviors were assessed via the Social Responsiveness Scale (SRS) questionnaire at age 12. Linear regression models adjusting for confounders were applied to estimate the association between pollutants and SRS scores. After adjusting for covariates, the association between NO2 and PM2.5 and SRS scores remained positive but were no longer statistically significant. Prenatal and first year exposure to NO2 were associated with total SRS T-scores with an estimated 0.4 point increase (95% CI: -0.7, 1.6) per 5.2 ppb increase in NO2 exposure and 0.7 point (95% CI: -0.3, 1.6) per 4.2 ppb increase in NO2 exposure, respectively. For PM2.5, a 2.6 µg/m3 increase in prenatal exposure was associated with a 0.1 point increase (95% CI: -1.1, 1.4) in SRS Total T-scores and a 1.3 µg/m3 increase first year of life was associated with a 1 point increase (95% CI: -0.2, 2.3). In summary, exposure to NO2 and PM2.5 during pregnancy and the first year of life were not significantly associated with higher autistic-like behaviors measured with SRS scores after adjustment of covariates. Additional research is warranted given prior studies suggesting air pollution contributes to ASD.

Pre- and postnatal exposure to secondhand tobacco smoke and cardiometabolic risk at 12 years: Periods of susceptibility.

BACKGROUND: To identify periods of heightened susceptibility to the association of secondhand tobacco smoke (SHS) exposure with cardiometabolic (CM) risk at age 12 years. METHODS: We used data from 212 adolescents from the HOME Study, a prospective pregnancy and birth cohort in Cincinnati, OH. Using multiple informant models, we estimated associations of maternal serum cotinine (mean of concentrations at 16 and 26 weeks of pregnancy) and children's serum cotinine concentrations (mean of concentrations at ages 1, 2, 3, and 4 years) with a CM risk summary score constructed of five risk components measured at age 12 years. We determined if these associations differed for pre- and postnatal exposure periods, and adolescent's sex. RESULTS: We found some evidence that the cotinine-outcome associations differed by exposure period and sex. Postnatal, but not prenatal, cotinine was associated with higher CM risk scores and individual CM risk component values (interaction p-values = 0.04 to 0.35). Each 10-fold increase in postnatal cotinine was associated with 0.57 (95% CI: 0.32, 1.45), 0.09 (95% CI: 0.13, 0.31), 0.14 (-0.08, 0.35), 0.07 (95% CI: 0.34, 0.48), and 0.11 (95% CI: 0.04, 0.27) higher CM risk, HOMA-IR, TG to HDL-C ratio, leptin to adiponectin ratio, and visceral fat area. Postnatal cotinine was associated with higher visceral fat area among females but not males (sex × period × cotinine interaction p-value = 0.01). CONCLUSIONS: Serum cotinine concentrations during the postnatal period had greater influence on adolescent's CM risk compared to the prenatal period, and these associations may be sex-specific. This study reinforces the need for ongoing public health interventions to minimize children's exposure to SHS.