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Background: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations. Method: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways. Results: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta. Conclusion: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta. [ABSTRACT FROM AUTHOR]

The article provides information about the growing concerns over perfluoroalkyl and polyfluoroalkyl substances (PFAS) and the proposed national standards by the Environmental Protection Agency (EPA) to limit PFAS concentrations in public drinking water supplies. It highlights the health risks associated with PFAS exposure, and the urgent need to address PFAS pollution to protect public health.

In the article, the author discusses the long-term effects of prenatal exposure to the per- and polyfluoroalkyl substances (PFAS) and the relationships between PFAS like perfluorooctane sulfonate (PFOS) on body mass index (BMI), risk of obesity, and accelerated growth. Also cited are the group of developmental toxicants like diethylstibesterol and tobacco smoke, and the links of prenatal hemodynamics and renal function with later-life body composition.

Summary: Introduction: Prevalence and risk factors for elevated glycated haemoglobin (HbA1c) and blood pressure (BP) are poorly understood among Pacific children. We examined associations of HbA1c and BP in 6–9 year‐olds with body mass index (BMI) at ages 2, 5, and BMI velocity between 2–9 years in Samoa. Methods: HbA1c (capillary blood) and BP were measured in n = 410 Samoan children who were part of an ongoing cohort study. Multilevel models predicted BMI trajectory characteristics. Generalized linear regressions assessed associations of childhood characteristics and BMI trajectories with HbA1c and BP treated as both continuous and categorical outcomes. Primary caregiver‐reported childhood characteristics were used as covariates. Results: Overall, 12.90% (n = 53) of children had high HbA1c (≥5.7%) and 33.17% (n = 136) had elevated BP. BMI at 5‐years and BMI velocity were positively associated with high HbA1c prevalence in males. A 1 kg/m2 per year higher velocity was associated with a 1.71 (95% CI: 1.07, 2.75) times higher prevalence of high HbA1c. In females, higher BMI at 5‐years and greater BMI velocity were associated with higher BP at 6–9 years (95% CI: 1.12, 1.40, and 1.42, 2.74, respectively). Conclusion: Monitoring childhood BMI trajectories may inform cardiometabolic disease screening and prevention efforts in this at‐risk population. [ABSTRACT FROM AUTHOR]

Introduction: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. Method: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. Results: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. Conclusion: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Exposure to per- and polyfluoroalkyl substances (PFAS) – endocrine disrupting chemicals – may increase cardiometabolic risk. We evaluated whether adolescent lifestyle factors modified associations between gestational PFAS exposure and cardiometabolic risk using a prospective cohort study. In 166 mother-child pairs (HOME Study), we measured concentrations of four PFAS in maternal serum collected during pregnancy. When children were age 12 years, we calculated cardiometabolic risk scores from visceral adiposity area, blood pressure, and fasting serum biomarkers. We assessed adolescent physical activity and Healthy Eating Index scores using the Physical Activity Questionnaire for Older Children (PAQ-C), actigraphy, and 24-h diet recalls. Using multivariable linear regression and weighted quantile sum regression, we examined whether physical activity or diet modified covariate-adjusted associations of PFAS and their mixture with cardiometabolic risk scores. Physical activity modified associations between perfluorooctanoic acid (PFOA) and cardiometabolic risk scores. Each doubling of PFOA was associated with worse cardiometabolic risk scores among children with PAQ-C scores < median (β:1.4; 95% CI:0.5, 2.2, n = 82), but not among those with PAQ-C scores ≥ median (β: 0.2; 95% CI: 1.2, 0.7, n = 84) (interaction p-value = 0.01). Associations were most prominent for insulin resistance, leptin-adiponectin ratio, and visceral fat area. We observed results suggesting that physical activity modified the association of PFAS mixture with cardiometabolic risk scores, insulin resistance, and visceral fat area (interaction p-values = 0.17, 0.07, and 0.10, respectively); however, the 95% CIs of the interaction terms included the null value. We observed similar, but attenuated patterns for PFOA and actigraphy-based measures of physical activity. Diet did not modify any associations. Physical activity or diet did not modify associations for other PFAS. Childhood physical activity modified associations of prenatal serum PFOA concentrations with children's cardiometabolic risk in this cohort, indicating that lifestyle interventions may ameliorate the adverse effects of PFOA exposure. • Child physical activity modified relations of prenatal PFOA with cardiometabolic risk. • Adverse relations of PFOA with cardiometabolic risk greater in children with less activity. • Associations were most prominent for cardiometabolic markers related to type 2 diabetes. • Children's diet did not modify associations. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss how studies of chemical mixtures and human health can be used as guides in the creation of policies and interventions to prevent the health effects of said mixtures to humans. Also cited are the tools used to analyze the health effects like the Bayesian kernel machine regression and weighted quantile sums regression, and the research showing the effectiveness of behavioral interventions in preventing the adverse health effects of chemicals like phthalates.

Early life phthalate exposures may disrupt metabolism but results from human studies are inconsistent and few have examined body composition during adolescence. We investigated associations of gestational and childhood urinary phthalate biomarker concentrations with body composition at age 12 years. We used data from 206 mother-child pairs in a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003 to 2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed fat and lean mass of the whole body and android and gynoid subregions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores. Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. We assessed effect measure modification by child sex using stratified models. Generally, urinary mono-benzyl phthalate (MBzP) concentrations were modestly associated with lower fat and lean mass. Each 10-fold increase in urinary MBzP concentrations during gestation and at ages 5 and 8 years was associated with a −0.34 (95%CI: −0.72, 0.05), −0.44 (95% CI: −0.83, −0.05), and −0.35 (95% CI: −0.71, 0.00) z-score difference in lean body mass index, respectively. Urinary monoethyl phthalate, mono-(3-carboxypropyl) phthalate, and summed di(2-ethylhexyl) phthalate metabolites were associated with greater lean mass at some exposure periods. Slightly weaker but similar patterns of association were found with other body composition measures; associations did not differ by child sex. While most associations were weak, exposure to certain phthalates during gestation and childhood may be associated with adolescent body composition, particularly lean mass. • Phthalate exposures are ubiquitous among pregnant women and children. • Phthalates may be metabolic disruptors that affect adolescent body composition. • Certain phthalates were associated with body composition, especially lean mass. • There was no consistent period of heightened susceptibility. [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]

Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. We analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. ICCs of OPEs were 0.17–0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97–9.15). Other OPE metabolites were not significantly associated with HDP. Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance. [ABSTRACT FROM AUTHOR]

The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26 weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12 years, we calculated BMD and BMC Z -scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z -score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z -score in males, and a 0.49 (95% CI: −0.13, 1.10) greater ultradistal radius BMD Z -score in females. In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health. • Gestation may be a particularly susceptible period for osteotoxicant exposure. • Phthalates are ubiquitous chemicals used in plastics and consumer products. • Studies of pregnancy phthalate exposure and offspring bone health are scarce. • Phthalate levels associated with greater adolescent bone mineral density and content. [ABSTRACT FROM AUTHOR]

• BDE-28 was positively associated with glucose during pregnancy in single- and multi-pollutant models. • Increases in BDE-28, BDE-47, and BDE-99 were associated with higher cholesterol. • Inverse associations were noted between BDE-153, MBP, and MBzP with cholesterol. • We did not find a consistent relationship with any EDC and blood pressure between the models. • No relationship was noted between BPA or PFAS with cardiometabolic indices during pregnancy between the models. Background: Toxicology studies have identified pregnancy as a window of susceptibility for endocrine disrupting chemicals (EDCs) and cardiometabolic indices in women. No study in humans, however, has examined EDC mixtures and cardiometabolic indices during pregnancy. Methods : We used the Health Outcomes and Measures of the Environment (HOME) Study to examine whether bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFAS), and phthalates are associated with blood pressure, glucose, and lipids in 388 pregnant women. We measured PBDEs and PFAS in serum at 16 weeks gestation, while BPA and phthalate metabolites were quantified in urine at 16 and 26 weeks gestation. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate covariate-adjusted associations of individual EDCs and their mixtures with cardiometabolic indices during pregnancy. Results : A 10-fold increase in BDE-28 was associated with a 13.1 mg/dL increase in glucose (95% Confidence Interval [CI] 2.9, 23.2) in linear regression. The BKMR model also identified BDE-28 as having a positive association with glucose. BDE-28, BDE-47, and BDE-99 were positively associated with total cholesterol in both single- and multi-pollutant models, whereas a suggestive negative association was noted with BDE-153. Mono-n-butyl phthalate (MBP) (β = -7.9 mg/dL, 95% CI −12.9, −3.0) and monobenzyl phthalate (MBzP) (β = −6.3 mg/dL, 95% CI −10.6, −2.0) were both associated with significant decreases in cholesterol in linear regression, but only MBzP was identified as an important contributor in the BKMR model. Conclusion : Overall, we observed positive associations between PBDEs with glucose and cholesterol levels during pregnancy, while negative associations were found between some phthalate biomarkers and cholesterol. No relationship was noted for BPA or PFAS with cardiometabolic indices during pregnancy across both models. [ABSTRACT FROM AUTHOR]

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 (β = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (β = -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 (β = 23 g; 95% CI: -25, 71) compared to those with higher educational status (β = -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. [ABSTRACT FROM AUTHOR]

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 (β = −0.50; 95% CI, −1.07 to 0.08) BMI z score among males but not among females (β = 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. [ABSTRACT FROM AUTHOR]

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 (β: 0.23; 95% CI: 0.08, 0.38) and lower satiety responsiveness (β: -0.14; 95% CI: -0.26, -0.02); in males, prenatal and postnatal cotinine was related to lower food responsiveness (prenatal: β: -0.25; 95% CI: -0.04, -0.06; postnatal: β: -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. [ABSTRACT FROM AUTHOR]

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. [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]

The association of prenatal exposure to organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) with respiratory outcomes has not been previously investigated in humans, despite reports that these chemicals can cross the placenta and alter lung development as well as immune functions. In a cohort of 342 pregnant women recruited between 2003 and 2006 in the greater Cincinnati, Ohio Metropolitan area, we measured indoor dust OPEs and RBFRs at 20 weeks of gestation and urinary OPEs at 16 and 26 weeks of gestation and at delivery. We performed generalized estimating equations and linear mixed models adjusting for covariates to determine the associations of prenatal OPEs and RBFRs exposures with adverse respiratory outcomes in childhood, reported every six months until age 5 years and with lung function at age 5 years. We used multiple informant modeling to examine time-specific associations between maternal urinary OPEs and the outcomes. Dust concentrations of triphenyl phosphate (TPHP) (RR: 1.40, 95% CI: 1.18–1.66), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (RR: 1.51, 95% CI: 1.23–1.85), and bis(2-ethylhexyl) tetrabromophthalate (RR: 1.57, 95% CI: 1.28–1.94) were associated with higher risk of wheezing during childhood. Dust TPHP concentrations were associated with higher risk of respiratory infections (RR: 1.43, 95% CI: 1.08–1.94), and dust tris-(2-chloroethyl) phosphate concentrations were associated with hay fever/allergies (RR: 1.11, 95% CI: 1.01–1.21). We also found that dust tris-(2-chloroethyl) phosphate loadings were associated with lower lung function. Urinary OPEs mainly at week 16 of gestation tended to be associated with adverse respiratory outcome, while bis(1-chloro-2-propyl) phosphate and diphenyl phosphate at delivery were associated with lower risk of hay fever/allergies. In-utero exposure to OPEs and RBFRs may be a risk factor for adverse respiratory outcomes in childhood, depending on the timing of exposure. • In-utero exposure to replacement brominated flame retardants and organophosphate esters tends to be associated with adverse childhood respiratory outcomes. • Urinary bis(1-chloro-2-propyl) phosphate (BCIPP) detection was associated with higher risk of wheeze at any of the prenatal sampling time points. • Urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at 16 weeks of gestation was associated with higher risk of wheeze. • Urinary bis-2-chloroethyl phosphate and BDCIPP at 16 weeks of gestation were associated with higher risk of respiratory infections. • BDCIPP and diphenyl phosphate around delivery were associated with lower risk of hay fever or allergies. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment.We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior.We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6–13 years and their parents. We estimated covariate‐adjusted associations of loge‐transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g‐computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children‐3 and Behavior Rating Inventory of Executive Function T‐scores (higher scores indicate more problem behaviors).This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non‐Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T‐scores (propyl paraben β$\beta \;$= 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β$\beta \;$= 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T‐scores (propyl paraben β$\beta \;$= 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β$\beta \;$= 1.6; 95% confidence interval: ‐0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T‐scores respectively. Higher paternal preconception (β$\beta \;$= 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception (β$\beta \;$= 1.1 95% confidence interval: ‐0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T‐scores in children, but the paraben mixtures was not.In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent‐reported child behaviors. [ABSTRACT FROM AUTHOR]

Modifiable factors, such as environmental exposures, can impact human fertility. The objective of this review is to summarize the potential effects of exposure to important endocrine-disrupting chemicals on male reproductive health. Most experimental and animal data demonstrate strong evidence for the negative effects of exposure to phenols, phthalates, pesticides, and perfluoroalkyl and polyfluoroalkyl substances on male reproductive health. Although evidence of negative associations in humans was overall strong for phthalates and pesticides, limited and inconclusive relationships were found for the other examined chemical biomarkers. Reasons for the discrepancies in results include but are not limited to, differences in study populations, exposure concentrations, number of samples collected, sample sizes, study design, and residual confounding. Additional studies are needed, particularly for newer phenols and perfluoroalkyl and polyfluoroalkyl substances, given the scarce literature on the topic and increasing exposures over time. [ABSTRACT FROM AUTHOR]

Background: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. Objectives: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. Population: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. Preliminary Results: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). Conclusions: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development. [ABSTRACT FROM AUTHOR]

Children are highly exposed to flame retardants in indoor environments, partly through inhalation. However, the associations of early life exposure to novel organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs) with adverse respiratory outcomes during childhood are unclear. We used a prospective birth cohort of 234 children recruited from the greater Cincinnati, Ohio metropolitan area between 2003 and 2006. OPFRs and RBFRs were analyzed in dust sampled from the homes' main activity room and the children's bedroom floor at child age 1 year. Caregivers reported subsequent respiratory symptoms every six months until child age 5 years and we measured forced expiratory volume in 1 s as well as peak expiratory flow (PEF) at child age 5 years. We performed generalized estimating equations and linear regression modeling adjusted for covariates to examine the exposure-outcome associations. Geometric means (GMs) (standard error [SE]) for dust concentrations were 10.27 (0.63) μg/g for total OPFRs (ΣOPFRs) and 0.48 (0.04) μg/g for total RBFRs (ΣRBFRs); GMs (SE) for dust loadings were 2.82 (0.26) μg/m2 for ΣOPFRs and 0.13 (0.01) μg/m2 for ΣRBFRs. Dust ∑OPFRs concentrations at age 1 year were associated with higher subsequent risks of wheezing (relative risk [RR]: 1.68, 95% confidence interval [CI]: 1.20–2.34), respiratory infections (RR: 4.01, 95% CI: 1.95–8.24), and hay fever/allergies (RR: 1.33, 95% CI: 1.10–1.60), whereas ∑OPFRs dust loadings at age 1 year were associated with higher risks of subsequent respiratory infections (RR: 1.87, 95% CI: 1.05–3.34) and hay fever/allergies (RR: 1.34, 95% CI: 1.19–1.51). PEF (mL/min) was lower with higher ∑OPFRs dust loadings (β: -12.10, 95% CI: -21.10, −3.10) and with the RBFR bis(2-ethylhexyl) tetrabromophthalate (β: -9.05, 95% CI: -17.67, −0.43). Exposure to OPFRs and RBFRs during infancy may be a risk factor for adverse respiratory outcomes during childhood. • We studied the associations of house dust organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs) during infancy with adverse respiratory outcomes. • Dust OPFRs and RBFRs levels were associated with higher risks of subsequent wheeze, respiratory infections, and/or hay fever/allergies. • Peak expiratory flow (PEF) during childhood was lower with higher OPFRs dust loadings in infancy. • PEF during childhood was also lower with bis(2-ethylhexyl) tetrabromophthalate dust loadings in infancy. [ABSTRACT FROM AUTHOR]

Improving indoor air quality is one potential strategy to reduce the transmission of SARS-CoV-2 in any setting, including nursing homes, where staff and residents have been disproportionately and negatively affected by the COVID-19 pandemic. Single group interrupted time series. A total of 81 nursing homes in a multifacility corporation in Florida, Georgia, North Carolina, and South Carolina that installed ultraviolet air purification in their existing heating, ventilation, and air conditioning systems between July 27, 2020,k and September 10, 2020. We linked data on the date ultraviolet air purification systems were installed with the Nursing Home COVID-19 Public Health File (weekly data reported by nursing homes on the number of residents with COVID-19 and COVID-19 deaths), public data on data on nursing home characteristics, county-level COVID-19 cases/deaths, and outside air temperature. We used an interrupted time series design and ordinary least squares regression to compare trends in weekly COVID-19 cases and deaths before and after installation of ultraviolet air purification systems. We controlled for county-level COVID-19 cases, death, and heat index. Compared with pre-installation, weekly COVID-19 cases per 1000 residents (−1.69; 95% CI, −4.32 to 0.95) and the weekly probability of reporting any COVID-19 case (−0.02; 95% CI, −0.04 to 0.00) declined in the post-installation period. We did not find any difference pre- and post-installation in COVID-19–related mortality (0.00; 95% CI, −0.01 to 0.02). Our findings from this small number of nursing homes in the southern United States demonstrate the potential benefits of air purification in nursing homes on COVID-19 outcomes. Intervening on air quality may have a wide impact without placing significant burden on individuals to modify their behavior. We recommend a stronger, experimental design to estimate the causal effect of installing air purification devices on improving COVID-19 outcomes in nursing homes. [ABSTRACT FROM AUTHOR]

Background: Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have examined low levels found in most Canadians. Vitamin D, which may have antioxidant activity, protects against PTB. Objectives: In this study, we investigated the impact of toxic metals (lead, mercury, cadmium and arsenic) on PTB and examined if maternal plasma vitamin D concentrations modify these associations. Methods: We investigated whether concentrations of metals in whole blood measured in early and late pregnancy were associated with PTB (<37 weeks) and spontaneous PTB in 1851 live births from the Maternal–Infant Research on Environmental Chemicals Study using discrete time survival analysis. We also investigated whether the risk of PTB was modified by first‐trimester plasma 25‐hydroxyvitamin D (25OHD) concentrations. Results: Of 1851 live births, 6.1% (n = 113) were PTBs and 4.9% (n = 89) were spontaneous PTB. A 1 μg/dL increase in blood lead concentrations during pregnancy was associated with an increased risk of PTB (relative risk [RR] 1.48, 95% confidence interval [CI] 1.00, 2.20) and spontaneous PTB (RR 1.71, 95% CI 1.13, 2.60). The risk was higher in women with insufficient vitamin D concentrations (25OHD <50 nmol/L) for both PTB (RR 2.42, 95% CI 1.01, 5.79) and spontaneous PTB (RR 3.04, 95% CI 1.15, 8.04). However, an interaction on the additive scale was not present. Arsenic was associated with a higher risk of PTB (RR 1.10, 95% CI 1.02, 1.19) and spontaneous PTB (RR 1.11, 95% CI 1.03, 1.20) per 1 μg/L. Conclusions: Gestational exposure to low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; individuals with insufficient vitamin D may be more susceptible to the adverse effects of lead. Given our relatively small number of cases, we encourage testing of this hypothesis in other cohorts, especially those with vitamin D‐deficient populations. [ABSTRACT FROM AUTHOR]

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]

Summary: Background: Eating behaviours are associated with childhood obesity, but their associations with cardiometabolic risk are less clear. Objectives: We evaluated cross‐sectional associations between eating behaviours and cardiometabolic risk among 185 adolescents (age 12.4 ± 0.7 years; 53% female; body mass index (BMI)‐z 0.72 ± 1.37) from Cincinnati, Ohio (HOME Study; enrolled 2003–2006). Methods: Caregivers assessed adolescents' eating behaviours with the Child Eating Behaviour Questionnaire. We computed adolescents' cardiometabolic risk scores based on HOMA‐IR, triglycerides to high‐density lipoprotein cholesterol ratio, adiponectin to leptin ratio, systolic blood pressure, and cross‐sectional area of fat inside the abdominal cavity. Using multivariable linear regression models, we estimated associations of eating behaviour subscales with cardiometabolic risk scores or individual risk components. Results: Emotional overeating (ß = 1.34, 95% CI: 0.67, 2.01), food responsiveness (ß = 0.99, 95% CI: 0.41, 1.57), and emotional undereating (ß = 0.64, 95% CI: 0.08, 1.21) were associated with higher cardiometabolic risk scores. Satiety responsiveness (ß = −0.79, 95% CI: −1.59, 0.00) was associated with lower cardiometabolic risk scores. Adjusting for adolescent BMI‐z at age 12 attenuated these associations, suggesting that adiposity may mediate these associations. Conclusion: Hedonistic eating behaviours were associated with higher cardiometabolic risk in these adolescents. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic—and its associated restrictions—have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes. Within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether there were pandemic-related changes in behavior that may be associated with environmental exposures. A total of 1535 participants from nine cohorts completed a survey via RedCap from December 2020 through May 2021. The questionnaire identified behavioral changes associated with the COVID-19 pandemic in expected directions, providing evidence of construct validity. Behavior changes reported by at least a quarter of the respondents include eating less fast food and using fewer ultra-processed foods, hair products, and cosmetics. At least a quarter of respondents reported eating more home cooked meals and using more antibacterial soaps, liquid soaps, hand sanitizers, antibacterial and bleach cleaners. Most frequent predictors of behavior change included Hispanic ethnicity and older age (35 years and older). Respondents experiencing greater COVID-related stress altered their behaviors more than those not reporting stress. These findings highlight that behavior change associated with the pandemic, and pandemic-related psychological stress often co-occur. Thus, prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic. Analyzing biomarker data in these participants will be helpful to determine if behavior changes reported associate with measured changes in exposure. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders emerge during childhood and adolescence and are frequently preceded by subsyndromal anxiety symptoms. Environmental toxicants, including gestational polybrominated diphenyl ether (PBDE) exposure, are associated with neuropsychiatric sequelae; however, the role of PBDEs as risk factors for anxiety in adolescence is unclear. Methods: Using data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled from 2003 to 2006, we investigated the relationship between gestational serum PBDE concentrations and anxiety symptoms in adolescents (N = 236). We measured five PBDE congeners (PBDE‐28, −47, −99, −100, and −153) at 16 ± 3 weeks of gestation and calculated their sum (∑PBDE). We assessed self‐reported anxiety symptoms using the Screen for Child Anxiety Related Emotional Disorders (SCARED) and depressive symptoms using the Children's Depression Inventory (CDI‐2) at age 12 years. We estimated the associations of maternal PBDE concentrations with child anxiety and depressive symptoms using multivariable linear regression and modified Poisson regression. Covariates included child sex, maternal race, maternal age at delivery, maternal marital status, maternal education, and household income at the 12‐year study visit as well as maternal depressive and anxiety symptoms. Sensitivity analyses were performed to control for maternal lead and mercury at delivery. Results: After adjusting for predetermined covariates, each doubling in maternal PBDE concentrations was associated with increased SCARED scores (e.g., for ∑PBDE, SCARED total score, β = 1.6 95% confidence interval [CI]: 0.3–2.9, p =.019) and a nonsignificant increase in depressive symptoms (e.g., for CDI total score, β =.8, 95% CI: −0.2–1.8, p =.11). Conclusions: Gestational serum PBDE concentrations just before mid‐pregnancy and during a period of active cortical and limbic neurogenesis, synaptogenesis and myelogenesis may be a risk factor for developing anxiety symptoms in early adolescence. [ABSTRACT FROM AUTHOR]

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. 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. We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑ 5 BDE: 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, log 10 -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. Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, −99, −100, ∑ 5 BDE), internalizing problems (BDE-28, -47, −99), functional impairment (BDE-28, ∑ 5 BDE), 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, ∑ 5 BDE) 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, ∑ 5 BDE). 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 BDE serum concentrations were associated with internalizing and externalizing behaviors in adolescence. • Gestational BDE concentrations were related to adolescent-reported internalizing behaviors, not caregiver-reported measures. • Caregiver-reported childhood externalizing behaviors remained associated with gestational BDE concentrations in adolescence. • Gestational BDE and caregiver-reported measures had stronger associations for externalizing than internalizing behaviors. [ABSTRACT FROM AUTHOR]

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. 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. 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

Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development. In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp). Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: −0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: −5.7; 95%CI: −10.3, −0.8, and %Δ: −4.1; 95%CI: −7.6, −0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: −5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: −7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: −9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: −17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: −16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: −3.7, 20.9). PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with −31.3% lower insulin (95%CI: −45.8, −12.9), −31.9% lower HOMA-IR (95%CI: −46.4, −13.4), and −9.4% lower leptin (95%CI: −17.3, −0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings. • Single and joint PFAS were positively associated with total and HDL cholesterol. • PFAS were also inversely associated with insulin, HOMA-IR, MCP-1, TNF- α, and leptin. • Contributors to joint PFAS associations often differed from single-PFAS findings. [ABSTRACT FROM AUTHOR]

Children are exposed to many trace elements throughout their development. Given their ubiquity and potential to have effects on children's neurodevelopment, these exposures are a public health concern. This study sought to identify trace element mixture‐associated deficits in learning behavior using operant testing in a prospective cohort. We included 322 participants aged 6–7 years recruited in Mexico City with complete data on prenatal trace elements measurements (third trimester blood lead and manganese levels, and & urine cadmium and arsenic levels), demographic covariates, and the Incremental Repeated Acquisition (IRA), an associative learning task. Weighted quantile sum (WQS) regression models were used to estimate the joint association of the mixture of all four trace elements and IRA performance. Performance was adversely impacted by the mixture, with different elements relating to different aspects of task performance suggesting that prenatal exposure to trace element mixtures yields a broad dysregulation of learning behavior. [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]

Eating behaviors are controlled by the neuroendocrine system. Whether endocrine disrupting chemicals have the potential to affect eating behaviors has not been widely studied in humans. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-A (BPA) concentrations were associated with children's eating behaviors. We used data from mother-father-child triads in the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6–13 years whose parent(s) previously enrolled in a fertility clinic-based prospective preconception study. We quantified urinary concentrations of 11 phthalate metabolites and BPA in parents' urine samples collected preconceptionally and during pregnancy. Parents rated children's eating behavior using the Child Eating Behavior Questionnaire (CEBQ). Using multivariable linear regression, accounting for correlation among twins, we estimated covariate-adjusted associations of urinary phthalate biomarkers and BPA concentrations with CEBQ subscale scores. This analysis included 195 children (30 sets of twins), 160 mothers and 97 fathers; children were predominantly non-Hispanic white (84%) and 53% were male. Paternal and maternal preconception monobenzyl phthalate (MBzP) concentrations and maternal preconception mono-n-butyl phthalate (MnBP) were positively associated with emotional overeating, food responsiveness, and desire to drink scores in children (β ′ s = 0.11 [95% CI: 0.01, 0.20]–0.21 [95% CI: 0.10, 0.31] per log e unit increase in phthalate biomarker concentration). Paternal preconception BPA concentrations were inversely associated with scores on food approaching scales. Maternal pregnancy MnBP, mono-isobutyl phthalate (MiBP) and MBzP concentrations were associated with increased emotional undereating scores. Maternal pregnancy monocarboxy-isononyl phthalate concentrations were related to decreased food avoiding subscale scores. In this cohort, higher maternal and paternal preconception urinary concentrations of some phthalate biomarkers were associated with increased food approaching behavior scores and decreased food avoiding behavior scores, which could lead to increased adiposity in children. • We explored preconception and pregnancy phthalates in relation to eating behaviors. • Parental preconception phthalates were associated with less food avoiding behaviors. • Preconception phthalates were associated with more food approaching behaviors. [ABSTRACT FROM AUTHOR]

The 2017–2018 U.S. PFAS exposure burden calculator was designed to provide a summary exposure score for per - and polyfluoroalkyl substances (PFAS) mixtures using targeted PFAS analyte data. Its aim was to place PFAS burden score estimates onto a common scale based on nationally representative U.S. reference ranges from 2017 to 2018, enabling comparisons of overall PFAS burden scores across studies even if they did not measure the same set of PFAS analytes. To use the U.S. PFAS exposure burden calculator for comparing the same mixture of PFAS compounds in similarly aged adolescents and their associations with cardiometabolic outcomes in the HOME Study and NHANES between 2015 and 2018. We applied the PFAS burden calculator to 8 PFAS analytes measured in the serum of adolescents from the HOME Study (Cincinnati, Ohio; age range 11–14 years; years: 2016–2019; n = 207) and NHANES (US; age range 12–14 years; years 2015–2018; n = 245). We used the non-parametric Mann-Whitney U test and chi-squared test to compare the two study samples. In both studies, we examined associations of PFAS burden scores with the same cardiometabolic outcomes, adjusted for the same core set of covariates using regression analyses. We conducted sensitivity analyses to verify robustness of exposure-outcome associations, by accounting for measurement error of PFAS burden scores. PFAS burden scores were significantly different (p = 0.004) between the HOME Study (median: 0.00, interquartile range − 0.37, 0.34) and the NHANES samples (median: 0.04, IQR -0.11, 0.54), while no significant difference was found for PFAS summed concentrations (p = 0.661). In the HOME Study, an interquartile (IQR) increase in PFAS burden score was associated with higher total cholesterol [7.0 mg/dL, 95% CI: 0.6, 13.4]; HDL [2.8 mg/dL, 95% CI: 0.4, 5.2]; LDL [5.9 mg/dL, 95% CI: 0.5, 11.3], insulin [0.1 log(mIU/L), 95% CI: 0.01, 0.2], and HOMA-IR [0.1, 95% CI: 0.01, 0.2]. In NHANES, an IQR increase in PFAS burden score was associated with higher diastolic blood pressure [2.4 mmHg, 95% CI: 0.4, 4.4] but not with other outcomes. Sensitivity analyses in the HOME Study and NHANES were consistent with the main findings. Performance of the U.S. PFAS exposure burden calculator was similar in a local versus national sample of adolescents, and may be a useful tool for the assessment of PFAS mixtures across studies. • A PFAS exposure burden calculator estimate a person's overall exposure burden to PFASs. • In the NHANES sample, adolescent PFAS exposure burden was associated with higher cholesterol and insulin resistance. • In the HOME Study sample, adolescent PFAS exposure burden was associated with higher diastolic blood pressure. • A standardized PFAS exposure burden metric can be useful for cross-study comparisons. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phthalate exposure is ubiquitous and may affect biological pathways related to regulators of blood pressure. Given the profound changes in vasculature during pregnancy, pregnant women may be particularly susceptible to the potential effects of phthalates on blood pressure. OBJECTIVES: We examined associations of phthalate exposure during pregnancy with maternal blood pressure trajectories from mid-pregnancy through 72 months postpartum. METHODS: Women with singleton pregnancies delivering a live birth in Mexico City were enrolled during the second trimester (푛 = 892). Spot urine samples from the second and third trimesters were analyzed for 15 phthalate metabolites. Blood pressure and covariate data were collected over nine visits through 72 months postpartum. We used linear, logistic, and linear mixed models; latent class growth models (LCGMs); and Bayesian kernel machine regression to estimate the relationship of urinary phthalate biomarkers with maternal blood pressure. RESULTS: As a joint mixture, phthalate biomarker concentrations during pregnancy were associated with higher blood pressure rise during mid-to-late gestation. With respect to individual biomarkers, second trimester concentrations of monobenzyl phthalate (MBzP) and di(2-ethylhexyl) phthalate biomarkers (ΣDEHP) were associated with higher third trimester blood pressure. Two trajectory classes were identified by LCGM, characterized by increasing blood pressure through 72 months postpartum ("increase-increase") or decreased blood pressure through 18 months postpartum with a gradual increase thereafter ("decrease-increase"). Increasing exposure to phthalate mixtures during pregnancy was associated with higher odds of being in the increase-increase class. Similar associations were observed for mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and dibutyl phthalate (ΣDBP) biomarkers. When specific time periods were examined, we observed specific temporal relationships were observed for RDEHP, MECPTP, MBzP, and ΣDBP. DISCUSSION: In our cohort of pregnant women from Mexico City, exposure to phthalates and phthalate biomarkers was associated with higher blood pressure during late pregnancy, as well as with long-term changes in blood pressure trajectories. [ABSTRACT FROM AUTHOR]

Objective: To explore windows of vulnerability to prenatal urinary phenol concentrations and preterm birth.Design: Prospective cohort.Setting: A large fertility center in Boston, Massachusetts.Patient(s): A total of 386 mothers who sought fertility treatment and gave birth to a singleton between 2005 and 2018.Intervention(s): None.Main Outcome Measure(s): Singleton live birth with gestational age <37 completed weeks.Result(s): Compared with women with non-preterm births, urinary bisphenol A (BPA) concentrations were higher across gestation among women with preterm births, particularly during mid-to-late pregnancy and among those with female infants. Second trimester BPA concentrations were associated with preterm birth (Risk Ratio [RR] 1.24; 95%CI: 0.92, 1.69), which was primarily driven by female (RR 1.40; 95%CI: 1.04, 1.89) and not male (RR 0.85; 95%CI 0.50, 1.46) infants. First trimester paraben concentrations were also associated with preterm birth (RR 1.17; 95%CI: 0.94, 1.46) and similarly the association was only observed for female (RR 1.46; 95% CI: 1.10, 1.94) and not male infants (RR 0.94; 95%CIC: 0.72, 1.23). First trimester urinary bisphenol S concentrations showed a suggested risk of preterm birth (RR 1.25; 95%CI: 0.82, 1.89), although the small case numbers precluded sex-specific examination.Conclusion(s): We found preliminary evidence of associations between mid-to-late pregnancy BPA and early pregnancy paraben concentrations with preterm birth among those with female infants only. Preterm birth risk may be compound, sex, and window specific. Given the limited sample size of this cohort, results should be confirmed in larger studies, including fertile populations. [ABSTRACT FROM AUTHOR]

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003–2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose–response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di- n -butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed. [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]

[Display omitted] • A non-persistent EDC mixture was associated with lower estradiol levels using BKMR. • The EDC mixture was negatively associated with testosterone and TSH using WQSR. • Associations of some EDCs with early-to-mid pregnancy hormones differ by fetal sex. • Some EDC & hormone relationships exhibit non-linearities and chemical interactions. Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. Illinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8–40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. In women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with −5.65% (95% CI: −9.79, −1.28) lower testosterone and −0.09 μIU/mL (95% CI: −0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: −0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with −1.77% (95% CI: −4.08, 0.58) lower TT4 and −0.18 μIU/mL (95% CI: −0.33, −0.03) lower TSH. We also identified select chemical interactions. Some biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes. [ABSTRACT FROM AUTHOR]

• We explored preconception & pregnancy phthalate biomarkers in relation to behavior. • Maternal preconception & pregnancy MBzP was associated with externalizing behaviors. • Higher parental preconception MCOP was associated with less externalizing behaviors. Epidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. We analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6–11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). This analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-log e unit increase; 95 % CI: −0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: −1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: −2.1, −0.4). In this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores. [ABSTRACT FROM AUTHOR]

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. To assess relationships of self-reported dietary quality and macronutrient intake with serum PFAS concentrations in adolescents. 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. 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. 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. • We estimated associations between diet and serum PFAS concentrations in adolescents. • Higher overall dietary quality associated with lower serum PFAS concentrations. • Diets higher in fruit or fiber associated with lower serum PFAS concentrations. • Understanding PFAS exposure pathways may help to prevent adverse health impacts. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to assess exposure to an OPE mixture in early life and its relationship to parent-reported child behavior. We measured urinary concentrations of three OPE metabolites, bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and diphenyl phosphate (DPHP), at pregnancy (16 and 26 weeks of gestation and delivery) and postnatal time points (ages 1, 2, 3, and 5 years) in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort in Cincinnati, Ohio, USA (enrolled 2003–2006, n = 219). We used latent variable analysis in structural equations models and quantile g-computation to investigate associations of a mixture of the three OPE metabolites with parent-reported child behaviors at 3 and 8 years, measured using the Behavioral Assessment System for Children, Second Edition. Higher log-transformed urinary OPE latent variable values at 16 weeks were associated with fewer externalizing problem behaviors (ß = −5.74; 95% CI = −11.24, −0.24) and fewer overall behavioral problems at age 3 years (ß = −5.26; 95% CI = −10.33, −0.19), whereas having higher OPEs at delivery was associated with poorer overall behavioral problems at age 3 years (ß = 2.87; 95% CI = 0.13, 5.61). OPE latent variable values at 16 weeks, 26 weeks, and delivery were not associated with child behavior at 8 years. However, higher OPE latent variable values at 3 years were associated with fewer externalizing behaviors at 8 years (ß = −2.62; 95% CI = −5.13, −0.12). The quantile g-computation estimates had directions largely consistent with the latent variable analysis results. Pregnancy and postnatal urinary OPE metabolite mixtures were associated with child internalizing, externalizing, and overall negative behaviors at 3 and 8 years, but we did not identify a consistent pattern in terms of the direction of the effects or a particularly sensitive time point. • We studied pregnancy and postnatal OPEs and child behavior in a longitudinal cohort. • We used latent variable analysis and quantile g-computation to assess OPE mixtures. • Pregnancy OPEs were associated with child behavior at 3 years. • The direction of associations and vulnerable time points were inconsistent. [ABSTRACT FROM AUTHOR]

To identify periods of heightened susceptibility to the association of secondhand tobacco smoke (SHS) exposure with cardiometabolic (CM) risk at age 12 years. 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. 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). 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. [Display omitted] • Cardiovascular disease is the leading cause of disability and death in the USA. • SHS exposure is associated with increased risk of CVD. • Postnatal cotinine is associated with higher CM risk during adolescence. • Associations between cotinine and CM risk components may be sex-specific. [ABSTRACT FROM AUTHOR]

Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003–2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with −15.3 mg/dL (95% CI: 27.5, −3.13 mg/dL) and −11.8 mg/dL (−22.0, −1.51 mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0 mg/dL (95% CI: 7.11, 31.1 mg/dL) higher LDL levels in males and −30.4 mg/dL (95% CI: 50.9, −9.8 mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner. • Phthalate exposures are ubiquitous among pregnant women and children. • Phthalates may be metabolic disruptors that affect cardiometabolic health. • Some phthalates were associated with lower lipid levels. • Associations varied by exposure period and child sex. [ABSTRACT FROM AUTHOR]

Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health. We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003–2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation. We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (β: 0.09; 95% CI: 0.02, 0.17) and aBMD (β: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (β: 0.16; 95% CI: 0.06, 0.26) and null for males (β: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females. In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture. • Gestational urinary 2,5-dichlorophenol concentrations were associated with greater distal radius bone mineral density. • Associations for gestational urinary benzophenone-3, bisphenol A, and triclosan were null. • The environmental phenol mixture was associated with greater distal radius bone mineral content and density. [ABSTRACT FROM AUTHOR]