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

Environmental exposures contribute to multiple diseases in children; yet, few pediatricians have training in pediatric environmental health (PEH), and few academic health centers have PEH expertise. To build national capacity in PEH, the Academic Pediatric Association (APA) launched a professional development program that since 2002 has encouraged the establishment of post-residency/post-doctoral training programs, supported a special interest group, and convened an annual mentored retreat for PEH trainees. Describe the APA's professional development program in PEH and assess its impact by tracking careers of former trainees. Careers were tracked through interviews with trainees and program directors supplemented by searches of institutional websites. Publication listings were obtained through PubMed. Publication impact was assessed using bibliometric and altmetric measures. Grant histories were accessed through the National Institutes of Health RePORTER project. Information on advocacy work was obtained through interviews with program directors. Fifty-five trainees (36 physicians and 19 health scientists) completed PEH training and attended the APA retreat between 2002 and 2017. Forty-one (75%) are pursuing academic careers, 11 are associate or full professors, 11 are practicing general pediatrics or a pediatric subspecialty, 2 are Centers for Disease Control and Prevention epidemiologists, and 1 is a data scientist. Forty-two former trainees (76%) listed "environment" or "environmental" in their job titles or on their websites. Former trainees have published 632 scientific papers. These papers have been cited 3094times, have a relative citation ratio of 2.97, and have been read or viewed 1,274,388times. Twenty-one former trainees have been awarded 43 National Institutes of Health grants. Trainees have developed education and advocacy skills by teaching medical students and residents, presenting grand rounds, preparing policy papers, presenting legislative testimony, and making presentations to public audiences. The APA's professional development program has contributed to the expansion of national capacity in PEH. Former trainees are populating the field, generating new knowledge, and moving into leadership positions. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFAS) are persistent endocrine disrupting chemicals found in industrial and commercial products. Previous research has shown that other endocrine disrupting chemicals such as phthalates and bisphenol A may alter circulating levels of vitamin D; however, no research has examined associations between PFAS and vitamin D biomarkers. We conducted a cross-sectional analysis of 7040 individuals aged 12 years and older participating in the 2003-2010 cycles of the United States National Health and Nutrition Examination Survey (NHANES). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and total 25-hydroxyvitamin D [25(OH)D] were measured in serum samples. We used multivariable linear regression to estimate covariate-adjusted differences in total 25(OH)D or prevalence odds of vitamin D deficiency per log2 change in PFAS concentrations. We also assessed potential effect measure modification by gender, age, and race/ethnicity. PFAS were detected in over 98% of the samples. In adjusted models, each 2-fold increase in PFOS was associated with 0.9 nmol/L (95% CI: 0.2, 1.5) lower total 25(OH)D concentrations, with associations significantly stronger among whites (β: -1.7; 95% CI: -2.6, -0.7) and individuals older than 60 years of age (β: -1.7; 95% CI: -2.9, -0.5). Each 2-fold increase in PFHxS was associated with 0.8 nmol/L (95% CI: 0.3, 1.3) higher total 25(OH)D, and this association was not modified by age, gender, and race/ethnicity. PFOA and PFNA were not associated with total 25(OH)D. When assessing prevalence odds of vitamin D deficiency, we observed similar patterns of association with PFAS concentrations. Our results suggest that some PFAS may be associated with altered vitamin D levels in the United States population, and associations may vary by chemical, age, and race/ethnicity. Prospective epidemiological studies are needed to confirm our findings and determine their implications for vitamin D-associated health outcomes in children and adults. [ABSTRACT FROM AUTHOR]

Abstract Background Animal studies suggest polybrominated diphenyl ethers (PBDEs) may be obesogens. However, epidemiologic studies investigating childhood exposure to PBDEs and adiposity are limited, with several reporting an inverse association. Objectives To investigate associations between repeated childhood PBDE concentrations and adiposity measures at age 8 years. Methods We examined 206 children from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (2003–2006). Serum PBDEs were measured at ages 1, 2, 3, 5, and 8 years. We used multiple imputation to estimate missing PBDE concentrations. At 8 years, we measured weight, height, waist circumference, and body fat percentage. We used multiple informant models to estimate age-specific associations between PBDEs and adiposity measures. Results We observed significant inverse associations between BDE-153 with all adiposity measures that became increasingly stronger with later childhood measurements. A 10-fold increase in BDE-153 at ages 1 and 8 years was associated with 2% (95% CI −3.9, −0.1) and 7% (95% CI −9.1, −4.7) lower body fat, respectively. No statistically significant associations were found with BDE-28, -47, -99, or -100. Child sex modified some associations; inverse associations between BDE-153 and body fat were stronger among boys, while positive and null associations were noted among girls. Conclusions Childhood BDE-153 concentrations were inversely associated with adiposity measures and these associations became stronger as BDE-153 measurements were more proximal to adiposity measures. Inverse associations could be attributed to reverse causality arising from greater storage of PBDEs in adipose tissue of children with higher adiposity. Highlights • Findings do not support postnatal PBDEs are associated with increased adiposity. • BDE-28, -47, -99, -100, and ∑PBDEs were not associated with adiposity at 8 years. • There was a pattern of inverse associations between BDE-153 and adiposity measures. • Child sex modified BDE-153 associations, with decreases in body fat % in males, but not in females. • Reverse causality may have resulted in inverse associations. [ABSTRACT FROM AUTHOR]

Abstract Traffic-related air and noise pollution may increase the risk for cardiovascular disorders, especially among susceptible populations like pregnant women. The objective of this study was to evaluate the association of exposure to traffic-related air pollution and traffic noise with blood pressure in pregnant women. We extracted systolic blood pressure (SBP) and diastolic blood pressure (DBP) at ≥20 weeks gestation, as well as hypertensive disorders of pregnancy from medical records in the HOME Study, a prospective pregnancy and birth cohort from Cincinnati, OH (n = 370). We estimated exposure to elemental carbon attributable to traffic (ECAT), 1 1 ECAT = elemental carbon attributable to traffic. a marker of traffic-related air pollution, at women's residences at ~20 weeks gestation using a validated land use regression model and traffic noise using a publicly available transportation noise model. We used linear mixed models and modified Poisson regression adjusted for covariates to examine associations of ECAT and traffic noise with blood pressure and hypertensive disorders of pregnancy risk, respectively. In adjusted models, we found a 1.6 (95% CI = 0.02, 3.3; p = 0.048) mm Hg increase in SBP associated with an interquartile range increase in ECAT concentration; the association was stronger after adjusting for traffic noise (1.9 mm Hg, 95% = 0.1, 3.7; p = 0.035). ECAT concentrations were not significantly associated with DBP or hypertensive disorders of pregnancy, and traffic noise was not associated with SBP, DBP, or hypertensive disorders of pregnancy. There was no evidence of a joint effect of traffic noise and ECAT on any outcome. In this cohort, higher residential traffic-related air pollution exposure at ~20 weeks gestation was associated with higher SBP in late pregnancy. It is important for future studies of traffic-related air or noise pollution to jointly consider both exposures and neighborhood characteristics given their correlation and potential cumulative impact on cardiovascular health. Highlights • We evaluated the association of traffic pollution with maternal blood pressure and hypertensive disorders of pregnancy risk. • Traffic-related air pollution exposure was associated with higher SBP in late pregnancy. • While traffic-related air and noise pollution were correlated, traffic noise was not associated with maternal blood pressure. • Women in low SES neighborhoods were more likely to be exposed to traffic noise and higher air pollution concentrations. [ABSTRACT FROM AUTHOR]

Abstract Objective We performed a systematic review of the epidemiology literature to identify the male reproductive effects associated with phthalate exposure. Data sources and study eligibility criteria Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of male reproductive effects in humans, and outcomes were selected for full systematic review based on data availability. Study evaluation and synthesis methods For each outcome, studies were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. Results The primary outcomes reviewed here are (number of included/excluded studies in parentheses): anogenital distance (6/1), semen parameters (15/9), time to pregnancy (3/5), testosterone (13/8), timing of pubertal development (5/15), and hypospadias/cryptorchidism (4/10). Looking at the overall hazard, there was robust evidence of an association between DEHP and DBP exposure and male reproductive outcomes; this was based primarily on studies of anogenital distance, semen parameters, and testosterone for DEHP and semen parameters and time to pregnancy for DBP. There was moderate evidence of an association between DINP and BBP exposure and male reproductive outcomes based on testosterone and semen parameters for DINP and semen parameters and time to pregnancy for BBP. DIBP and DEP were considered to have slight evidence of an association. For DIBP, the less conclusive evidence was attributed to a more limited literature base (i.e., fewer studies) and lower exposure levels in the population, decreasing the ability to observe an effect. For DEP, the findings were consistent with experimental animal data that suggest DEP does not haves as strong an anti-androgenic effect as other phthalates. Conclusions and implications of key findings Overall, despite some inconsistencies across phthalates in the specific outcomes associated with exposure, these results support that phthalate exposure at levels seen in human populations may have male reproductive effects, particularly DEHP and DBP. The relative strength of the evidence reflects differing levels of toxicity as well as differences in the range of exposures studied and the number of available studies. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA. Highlights • Phthalate exposures at levels seen in human populations may have male reproductive effects, particularly DEHP and DBP. • The effects with the strongest associations with phthalate exposures were semen parameters and testosterone in adult men. • For DIBP and DINP, there is inadequate sensitivity in the available studies. It would be inappropriate to conclude that substituting these for DBP or DEHP would be health protective. [ABSTRACT FROM AUTHOR]

Abstract Background Despite evidence from toxicological studies describing the potential neurotoxicity of perfluoroalkyl substances (PFAS), their role in neurodevelopment remains uncertain amid inconsistent findings from epidemiological studies. Methods Using data from 218 mother-child dyads from the Health Outcomes and Measures of the Environment Study, we examined prenatal and childhood (3 and 8 years) serum concentrations of four PFAS and inattention, impulsivity, and visual spatial abilities. At 8 years, we used the Conners' Continuous Performance Test-II to assess attention and impulse control and the Virtual Morris Water Maze (VMWM) to measure visual spatial abilities. Results In multiple informant models, there was no evidence to indicate that prenatal or childhood PFAS are associated with attention. However, there was an inverse association between prenatal ln-perfluorooctanoate (PFOA) and errors of commission (β = −2.0, 95% Confidence Interval [CI] −3.8, −0.3). Ln-perfluorononanoate (PFNA) at 3 years was associated with longer (poorer) VMWM completion times of 3.6 seconds (CI 1.6, 5.6). However, higher concurrent concentrations of ln-perfluorohexane sulfonate (PFHxS) (β = −2.4 s, 95% CI −4.4, −0.3) were associated with shorter (better) times. Higher prenatal PFHxS was positively associated with percentage of traveling distance in the correct quadrant (β = 4.2%, 95% CI 0.8, 7.7), indicating better performance. Conclusion Findings were mixed for prenatal and childhood PFAS concentrations and visual spatial abilities. There is not enough evidence to support that PFAS are associated with visual spatial abilities as assessed by the VMWM or CPT-II measures of inattention or impulsivity in children at age 8 years. Highlights • Prenatal and childhood PFAS are not associated with CPT-II measures of inattention at 8 years. • Inconsistent associations were noted between PFNA and PFHxS with VMWM performance at 8 years. • Findings do not support associations between PFAS and VMWM measures of visual spatial abilities. [ABSTRACT FROM AUTHOR]

Background Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. Methods We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003–2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ± 3 weeks gestation and in child serum at 1–3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. Results Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI −40.8%, −11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT 3 ). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T 4 (FT 4 ) in males. Prenatal ∑PBDEs were not associated with TT 4 , FT 4 , or total T 3 . Conclusions These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males. [ABSTRACT FROM AUTHOR]

Background Exposure to triclosan, an antimicrobial chemical, is ubiquitous among pregnant women and may reduce thyroid hormone levels that are important for fetal neurodevelopment. Few studies have examined the association between prenatal triclosan exposure and children's neurobehavior. Objective We investigated the relationship of prenatal urinary triclosan concentrations with children's behavior and cognitive abilities at age three years in a prospective pregnancy and birth cohort in Canada. Methods We measured triclosan in urine samples collected at ~12 weeks of gestation in 794 Canadian women enrolled in a prospective pregnancy and birth cohort study (MIREC) from 2008 to 2011. Around age 3 years, we assessed children's cognitive abilities using the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III), and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's problem and reciprocal social behaviors using the Behavior Assessment System for Children-2 (BASC-2) and Social Responsiveness Scale-2 (SRS-2), respectively. Results After adjusting for confounders using multivariable linear regression, triclosan was not associated with most of the 30 examined neurobehavioral scales. Each 10-fold increase in triclosan was associated with better WPPSI-III picture completion scores (β: 0.2; 95% CI: 0,0.5) and BASC-2 externalizing (β: −0.5; 95% CI: −1.1, 0) and hyperactivity (β: −0.6; 95% CI: −1.2, −0.1) scores, suggesting less externalizing and hyperactive behaviors. Child sex did not modify these associations. Conclusions In this cohort, urinary triclosan concentrations measured once in early pregnancy were not associated with most assessed aspects of neurobehavior and weakly associated with a few others, but not in the hypothesized direction. [ABSTRACT FROM AUTHOR]

Background Prenatal phthalate exposure has been inconsistently associated with fetal growth and infant birth weight. However, the effect of exposure during the paternal and maternal preconception period remains understudied. Objectives To investigate associations of paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations with birth weight. Methods The study comprised 364 singletons born to 364 mothers and 195 fathers (195 couples) from the EARTH Study, a prospective cohort of couples from Boston, MA. Births were categorized by mode of conception: in-vitro fertilization based (IVF) (n = 208) or non-IVF based (n = 156, intrauterine insemination or non-medically assisted/natural conception). We measured urinary concentrations of eleven phthalate metabolites in maternal (n = 1425) and paternal (n = 489) preconception and maternal prenatal (n = 781) samples. Birth weight was abstracted from delivery records. Covariate-adjusted associations between log e -phthalate metabolite concentrations and birth weight were evaluated separately by mode of conception using multivariable linear regression. Results Each log e -unit increase in paternal urinary concentration of the sum of di(2-ethylhexyl) phthalate (ΣDEHP) metabolites was associated with a 90 gram (95% CI: − 165, − 15) decrease in birth weight among IVF singletons, but not among non-IVF singletons (18 g; 95% CI: − 76, 113). Additional adjustment for maternal prenatal ΣDEHP concentrations modestly strengthened findings among IVF singletons. While few associations were found with maternal preconception phthalate metabolites, we observed an inverse relationship between several maternal prenatal urinary phthalate metabolite concentrations and birth weight among IVF singletons in covariate-adjusted models. However, with further adjustment for specific paternal phthalate metabolite concentrations, these associations were attenuated and no longer significant. Conclusions Paternal preconception urinary concentration of ΣDEHP metabolites was associated with a decrease in birth weight among IVF-conceived singletons. These results, if replicated, highlight the importance of preconception health, especially among subfertile couples. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific. [Display omitted] • BCEP was positively associated with gestation age and inversely with preterm birth. • DPHP was positively associated with gestation age and inversely with preterm birth. • BCEP was inversely associated with birth weight and length z-scores in females. • DNBP was inversely associated with the ponderal index at birth in males. • Associations of OPEs and pregnancy outcomes might be window- and infant sex-specific. [ABSTRACT FROM AUTHOR]

Background: Endocrine-disrupting chemicals may alter glucose homeostasis, especially during pregnancy. Biomonitoring studies suggest ubiquitous human exposure to organophosphate esters (OPEs), chemicals with endocrine-disrupting capabilities. Few studies have examined the association between maternal exposure to OPEs and blood glucose during pregnancy.Methods: With data from 301 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA, we examined whether OPE concentrations were associated with changes in blood glucose. We quantified four OPE metabolites in maternal spot urine samples collected at 16- and 26-weeks pregnancy. We extracted results from the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) via medical chart review. Women with GCT ≥ 140 mg/dL or any abnormal values in OGTT (≥ 95 mg/dL fasting glucose, ≥ 180 mg/dL 1-h glucose, ≥ 155 mg/dL 2-h glucose, ≥ 140 mg/dL 3-h glucose) were defined as having elevated glucose levels. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of individual OPE metabolites and OPE mixtures with blood glucose levels during pregnancy. We used modified Poisson regression to estimate the associations of OPE metabolite concentrations with elevated glucose levels. We further examined effect measure modification by maternal characteristics (age, pre-pregnancy body mass index [BMI], and race/ethnicity).Results: Diphenyl phosphate (DPHP) had the highest geometric mean concentration of the urinary OPE metabolites (1.83 μg/L at 16 weeks, 1.24 μg/L at 26 weeks). Thirty women (10.0%) had elevated glucose levels. Individual OPE metabolites or their mixtures were not significantly associated with continuous GCT results. We did not observe effect measure modification by maternal age, pre-pregnancy BMI categories, or race/ethnicity. Compared with women in the 1st tertile of average DPHP of 16- and 26 weeks of pregnancy, women in the 3rd tertile tended to have a reduced risk of elevated glucose levels (RR = 0.41, 95% CI = 0.16-1.06, p for trend = 0.06).Conclusion: In this cohort, maternal urinary OPE metabolite concentrations were weakly associated with blood glucose levels during pregnancy. [ABSTRACT FROM AUTHOR]

The 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]

• There is limited evidence of neurodevelopmental effects of phthalate exposure in humans. • The strongest evidence is for motor effects and BBP exposure in girls. • Evidence gaps need to be filled before concluding that there are minimal neurodevelopmental effects. We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure. Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of neurodevelopmental effects in humans, and outcomes were selected for full systematic review based on data availability. Studies of neurodevelopmental effects were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. For studies of cognition and motor effects in children ≤4 years old, a random effects meta-analysis was performed. The primary outcomes reviewed here are (number of studies in parentheses): cognition (14), motor effects (9), behavior, including attention deficit hyperactivity disorder (20), infant behavior (3), and social behavior, including autism spectrum disorder (7). For each phthalate/outcome combination, there was slight or indeterminate evidence of an association, with the exception of motor effects for BBP, which had moderate evidence. Overall, there is not a clear pattern of association between prenatal phthalate exposures and neurodevelopment. There are several possible reasons for the observed null associations related to exposure misclassification, periods of heightened susceptibility, sex-specific effects, and the effects of phthalate mixtures. Until these limitations are adequately addressed in the epidemiology literature, these findings should not be interpreted as evidence that there are no neurodevelopmental effects of phthalate exposure. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA. [ABSTRACT FROM AUTHOR]

The field of environmental epidemiology has been using "-omics" technologies, including the exposome, metabolome, and methylome, to understand the potential effects and biological pathways of a number of environmental pollutants. However, the majority of studies have focused on a single disease or phenotype, and have not systematically considered patterns of multimorbidity and whether environmental pollutants have pleiotropic effects. These questions could be addressed by examining the relation between environmental exposures and the phenome – the patterns and profiles of human health that individuals experience from birth to death. By conducting Phenome Wide Association Studies (PheWAS), we can generate new hypotheses about new or poorly understood exposures, identify novel associations for established toxicants, and better understand biological pathways affected by environmental pollutants. In this article, we provide a conceptual framework for conducting PheWAS in environmental epidemiology and summarize some of the advantages and challenges to using the PheWAS to study environmental pollutant exposures. Ultimately, by adding the PheWAS to our "-omics" toolbox, we could substantially improve our understanding of the potential health effects of environmental pollutants. • Epidemiology has not considered whether pollutants have pleiotropic effects. • The phenome is the patterns/profiles of disease experienced from birth to death. • Phenome Wide Association Studies (PheWAS) examine a pollutant and all phenotypes. • Using PheWAS could improve our understanding of the health effects of pollutants. [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]

Objectives: To examine whether parents' concerns about environmental chemical exposures were associated with urinary phthalate and phenol concentrations in their school-age children.Study Design: In a prospective cohort of 218 mother-child pairs from Cincinnati, Ohio (2010-2014), we measured 11 phthalate metabolites and 5 phenols in urine samples when children were age 8 years and used questionnaire data from caregivers. We estimated the covariate-adjusted percent difference in phthalates and phenols among children of parents who expressed concern about environmental chemical exposures compared with children whose parents did not.Results: Concentrations of 4 phthalates, bisphenol S, and bisphenol A were lower among children whose parents expressed concern about environmental chemicals (n = 122) compared with those who did not (n = 96). Di-2-ethylhexyl phthalate metabolites, bisphenol S, and bisphenol A concentrations were 23% (95% CI -38, -5), 37% (95% CI -49, -21), and 13% (95% CI -26, 3) lower, respectively, among children whose parents expressed concern compared with those whose parents did not. Triclosan concentrations were 35% greater (95% CI -2, 87) among children whose parents expressed concern compared with children whose parents did not.Conclusions: Parental concern about environmental chemicals was associated with lower childhood urine concentrations of several phthalates and phenols; unexpectedly, parental concern was associated with greater triclosan concentrations. These results suggest that parental concern may be an important factor in mitigating children's phthalate and phenol exposures. [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]

Few studies have considered household interventions for reducing endocrine disrupting chemical (EDC) exposures. We conducted a secondary analysis of a randomized controlled trial, originally designed to reduce lead exposure, to evaluate if the intervention lowered EDC exposures in young children. Study participants were children from the Cincinnati, Ohio area (n = 250, HOME Study). Prenatally, families received a housing intervention that included paint stabilization and dust mitigation, or as a control, injury prevention measures. At 24-months, we measured organophosphate esters (OPEs) and phthalates or their metabolites in dust and urine. We measured perfluoroalkyl substances (PFAS) in dust and serum at 24- and 36-months, respectively. We assessed associations between dust and biomarker EDCs using Spearman correlations, characterized EDC mixtures via principal components analysis, and investigated treatment effects using linear regression. To mitigate selection bias, we fit statistical models using inverse probability of retention weights. Correlations between dust EDCs and analogous biomarkers were weak-to-moderate (ρ's ≤ 0.3). The intervention was associated with 23 % (95 % CI: −38, −3) lower urinary DEHP metabolites and, in a per-protocol analysis, 34 % lower (95 % CI: −55, −2) urinary MBZP. Additionally, among Black or African American children, the intervention was associated with lower serum concentrations of several PFAS (e.g., −42 %; 95 % CI: −63, −8 for PFNA). Household interventions that include paint stabilization and dust mitigation may reduce childhood exposures to some phthalates and PFAS in Blacks/African Americans. These findings highlight the need for larger studies with tailored and sustained housing interventions. [ABSTRACT FROM AUTHOR]

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]

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]

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]

• PBDEs and PFAS during pregnancy may play a role in the pathogenesis of depression. • BDI-II was used to assess pregnancy and postpartum depressive symptoms. • PBDEs during pregnancy were associated with higher depressive symptoms in mothers. • ∑PBDEs were associated with higher risk of mothers having a high BDI-II trajectory. • Findings between PFAS during pregnancy and BDI-II scores were not significant. Experimental studies in rodents suggest that polybrominated diphenyl ethers (PBDEs) and poly- and perfluoroalkyl substances (PFAS) may contribute to depressive symptoms. Few studies have examined the impact of these chemicals on depression in adults. Objective : To examine the associations between serum PBDE and PFAS concentrations during pregnancy and repeated measures of depressive symptoms in women assessed from pregnancy to 8 years postpartum. Methods : This study was based on 377 women from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (USA). PBDEs (BDE-28, -47, -99, -100, -153, and ∑PBDEs) and PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorohexane sulfonate [PFHxS], perfluorononanoate [PFNA]) were quantified in maternal serum at 16 ± 3 weeks gestation. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II) at ~20 weeks gestation and up to seven times during postpartum visits (4 weeks, 1, 2, 3, 4, 5, and 8 years). We used linear mixed models to estimate covariate-adjusted associations between chemical concentrations and repeated measures of BDI-II. Multinomial logistic regression models were used to estimate the relative risk ratios of having a medium or high depression trajectory. Results : We found that a 10-fold increase in BDE-28 at 16 ± 3 weeks gestation was associated with significantly increased BDI-II scores (β = 2.5 points, 95% confidence interval [CI] 0.8, 4.2) from pregnancy to 8 years postpartum. Significant positive associations were also observed with BDE-47, -100, -153, and ∑PBDEs. A 10-fold increase in ∑PBDEs was associated with a 4.6-fold increased risk (95% CI 1.8, 11.8) of a high trajectory for BDI-II compared to a low trajectory. We observed no significant associations between PFAS and BDI-II scores. Conclusion : PBDEs during pregnancy were associated with more depressive symptoms among women in this cohort. [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]

We performed a systematic review of the epidemiology literature to identify the female reproductive and developmental effects associated with phthalate exposure. Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of female reproductive and developmental effects in humans, and outcomes were selected for full systematic review based on data availability. For each outcome, studies were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. The primary outcomes reviewed here are (number of included/excluded studies in parentheses): pubertal development (5/13), time to pregnancy (3/4), preterm birth (8/12), and spontaneous abortion (5/0). Among these outcomes, preterm birth had moderate evidence of a positive association with phthalate exposure (specifically DEHP, DBP, and DEP). Exposure levels for BBP, DIBP, and DINP were generally lower than for the phthalates with an observed effect, which may partially explain the difference due to lower sensitivity. Other phthalate/outcome combinations were considered to have slight or indeterminate evidence of an association. Overall, these results support that some phthalates may be associated with higher odds of preterm birth in humans, though there is some remaining inconsistency. More evidence is needed on the mechanism and relevant exposure window for this association. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA. • Phthalate exposures are associated with higher odds of preterm birth. • Associations with preterm birth are strongest for DEHP, DBP, and DEP. • Low exposure levels and fewer studies reduced sensitivity of the review for other phthalates. • Evidence for other female reproductive and developmental effects is less conclusive. • Integration with other lines of evidence would strengthen analyses of causality. [ABSTRACT FROM AUTHOR]

Triclosan exposure may decrease circulating thyroxine levels or cause neuron apoptosis, which in turn may adversely affect neurodevelopment. However, few studies have examined the association of early life triclosan exposure with child behavior. To quantify the association between early-life triclosan exposure and child behavior at age 8-years in 202 mother-child pairs from the HOME study (Cincinnati, OH; enrolled: 2003–2006). We quantified urinary triclosan concentrations up to 3 times in mothers (16-weeks, 26-weeks, and delivery) and up to 6 times in children (1, 2, 3, 4, 5, and 8 years). Parents rated children's problem behaviors at age 8-years using the Behavioral Assessment System for Children-2 (BASC-2). Adjusting for covariates and accounting for exposure measurement error, we estimated changes in behavior problem scores per 10-fold increase in mean gestational and childhood triclosan concentrations. In addition, we estimated sex-specific associations. Child sex modified the association of gestational and childhood triclosan with several BASC-2 scales (sex × triclosan p-values < 0.2). In boys, increasing gestational triclosan was associated with higher behavioral symptom index (β: 4.5; 95% CI: 1.0, 8.1), externalizing problems (β: 5.0; 95% CI: 1.2, 9.0), attention problem (β: 6.6; 95% CI: 2.4, 11), hyperactivity (β: 6.4; 95% CI: 2.1, 11), and somatization (β: 3.8; 95% CI: 0.3, 7.3) scores. In contrast, triclosan-BASC-2 associations in girls were generally null and not statistically significant. We observed similar patterns of associations between childhood triclosan and these same behavioral scores; however, their magnitude decreased substantially after adjusting for gestational triclosan and associations were not statistically significant. In this cohort, increasing gestational and childhood urinary triclosan concentrations were associated with higher behavior problem scores in 8-year old boys, but not girls. • We measured urinary triclosan concentrations up to nine times between the 2nd trimester of pregnancy and age 8-years. • We assessed parent-reported child problem behaviors at age 8 years. • We used a regression-calibration approach to account for triclosan exposure measurement error. • Urinary triclosan concentrations were associated with externalizing problem, attention, and hyperactivity scores in boys, but not girls. [ABSTRACT FROM AUTHOR]

Abstract Background Days of extreme temperature may be associated with transiently higher risk of preterm birth, but prior studies have been limited and results have been heterogeneous. Objectives To evaluate the association between days of extreme heat and cold and risk of preterm birth among ~32 million live singleton births between 1989 and 2002 across 403 counties in the contiguous United States (US). Methods We used a distributed lag nonlinear model to estimate the association between population-weighted daily mean temperature and risk of preterm birth in each county and then pooled results across geographic regions and climate zones. We defined extreme heat and cold as the 95th and 5th percentile of the county-specific temperatures, respectively. Results Preterm birth accounted for 9.3% of deliveries. There was a monotonic association between ambient temperature and risk of preterm birth. Days of extreme heat and cold were associated with a relative risk of preterm birth of 1.025 (95% CI: 1.015, 1.036) and 0.985 (95% CI: 0.976, 0.993) over the subsequent four days, respectively, relative to the county-specific median temperature. If causal, the fraction of preterm births attributable to extreme heat was 0.17% (empirical 95% CI: 0.14%, 0.19%), corresponding to 154 (empirical 95% CI: 127, 173) preterm births per million births. Extreme heat was more strongly associated with preterm birth in regions with colder and drier climates, and among younger women. Days of extreme cold temperature were associated with lower rather than higher risk of preterm birth. Conclusions Days of extreme heat, but not extreme cold, are associated with higher risk of preterm birth in the contiguous US. If causal, these results may have important implications for the management of pregnant women during forecasted periods of extreme heat. Highlights • We examined the association between extreme temperature and PTB in the contiguous US. • Days of extreme heat were associated with higher risk of preterm birth. • The association was stronger in regions with typically colder and drier climates. [ABSTRACT FROM AUTHOR]

Abstract Background Exposure to some environmental chemicals is ubiquitous and linked to a variety of adverse outcomes, including children's health. While few studies have assessed the contribution of both male and female exposures to children's health, understanding the patterns of couple's exposure is needed to understand their joint effects. Objective We assessed the correlation patterns between male and female partners' concentrations of 37 environmental chemical biomarkers. We also assessed the temporal reliability of the biomarkers within couples. Methods We calculated Spearman pairwise correlations between specific gravity adjusted urinary biomarker concentrations and hair mercury concentrations among 380 couples enrolled in the Environment and Reproductive Health (EARTH) study at the Massachusetts General Hospital Fertility Center (2004–2017). We calculated intra-class correlation coefficients (ICCs) for couple's biomarkers to assess the temporal variability of these exposures within a couple using multiple paired-samples from couples. Results All biomarkers were positively correlated within couples (range: 0.05 for tert -butylphenyl phenyl phosphate to 0.66 for triclosan). In general, the biomarkers with the highest within couple correlation were those of chemicals for which diet (e.g., di(2-ethylhexyl) phthalate), personal care products use (e.g., triclosan, benzophenone-3), and the indoor environment (e.g., 2,5-dichlorophenol) are considered primary exposure sources. Most other biomarkers were moderately correlated (0.3–<0.6). Similar patterns of temporal reliability were observed across biomarkers. Conclusions Urinary concentrations of several biomarkers were mostly moderately correlated within couples, suggesting similar exposure sources. Future epidemiological studies should collect samples from both partners to be able to accurately determine the contribution of maternal and paternal exposures to offspring health. Highlights • Understanding the patterns of couple's exposure is needed to understand their joint effects. • All 37 environmental biomarkers were positively correlated within couples. • Correlations were moderately high for chemicals with diet, personal products, and indoor environment are primary sources. • Similar patterns were observed across biomarkers for measures of temporal reliability. [ABSTRACT FROM AUTHOR]

Highlights • Cord blood adiponectin was positively associated with children's full-scale IQ. • Cord blood adiponectin was positively associated with children's performance IQ. • Cord blood adiponectin was positively associated with children's working memory. Abstract Background Adipocytokines may play a role in fetal programming of neurodevelopment. We aimed to investigate the associations between cord blood adipocytokine concentrations and children's intelligence test scores. Methods We used data from two ongoing pregnancy cohorts in North America: the Maternal-Infant Research on Environmental Chemicals (MIREC, n = 429) and Health Outcomes and Measures of the Environment (HOME, n = 183) Studies. Umbilical cord blood adipocytokine concentrations were measured using enzyme-linked immunosorbent assays. We assessed children's Intelligence Quotient (IQ) and its components using the Wechsler Preschool and Primary Scales of Intelligence-III or Wechsler Intelligence Scale for Children-IV. We used linear regression and linear mixed models to estimate associations between log 2 -transformed adipocytokine concentrations and children's IQ after adjusting for sociodemographic, perinatal, and child factors. Results After adjusting for covariates, cord blood adiponectin was positively associated with children's full-scale IQ scores at age 3 years in the MIREC Study (β = 1.4, 95% confidence interval [CI]: 0.2, 2.5) and at ages 5 and 8 years in the HOME Study (β = 1.7, CI: −0.1, 3.5). Adiponectin was positively associated with performance IQ in both studies (MIREC: β = 2.0, CI: 0.7, 3.3; HOME: β = 2.2, CI: 0.5, 3.9). Adiponectin was positively associated with working memory composite scores at age 8 in the HOME Study (β = 3.1, CI: 1.0, 5.2). Leptin was not associated with children's IQ in either study. Conclusions Cord blood adiponectin was associated with higher full-scale and performance IQ and working memory composite scores in children. Future studies are needed to explore the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Abstract Background Toxicological studies highlight the potential neurotoxicity of perfluoroalkyl substances (PFAS) during fetal development. However, few epidemiological studies have examined the impact of childhood PFAS on neurodevelopment. Methods We employed data from 208 children in the Health Outcomes and Measures of the Environment Study, a birth cohort (Cincinnati, OH), to examine associations of six serum PFAS concentrations measured at 3 and 8 years with executive function assessed at 8 years using the validated parent-completed Behavior Rating Inventory of Executive Function survey. We used multiple informant models to identify susceptible windows of neurotoxicity to PFAS and executive function. We investigated trajectories of PFAS concentrations and whether sex modified these associations. Results Each ln-increase in perfluorononanoate (PFNA) at 8 years was associated with a 3.4-point increase (95% CI 0.4, 6.3) in metacognition score, indicating poorer function. Children with PFNA above the median at 8 years had poorer global executive functioning compared to children with concentrations consistently below median levels (β = 6.5, 95% CI 0.2, 12.9). Higher concurrent PFNA was associated with poorer behavior regulation among males, while associations among females were null (p PFNA × sex = 0.018). Children with higher concurrent perfluorooctanoate (PFOA) had increased odds of being at risk of having clinical impairments in metacognition (OR = 3.18, 95% CI 1.17, 8.60). There were no associations between perfluorooctane sulfonate and perfluorohexane sulfonate and executive function. Conclusions PFNA and PFOA at 8 years, but not 3 years, may be related to poorer executive function at 8 years. Results need to be confirmed in cohort studies with larger sample sizes. Highlights • PFAS concentrations at age 3 years were not associated with executive function at age 8 years. • Concurrent PFNA was associated with impairments in metacognition and global executive function at 8 years. • A sexually dimorphic relationship may be present, with males more sensitive to PFNA neurotoxicity. • Childhood PFNA and PFOA, to a lesser extent, may be neurotoxic with regard to executive function. [ABSTRACT FROM AUTHOR]

Background: Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent.Objectives: In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns.Methods: We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n = 202) and cord serum at delivery (n = 276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones.Results: With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT4) decreased by 0.52 μg/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT4 (WQS beta = -0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta = -0.11; 95% CI: -0.20, -0.03) and TT4 (WQS beta = -0.53; 95% CI: -0.90, -0.16).Conclusion: Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology. [ABSTRACT FROM AUTHOR]

Background Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment. Objective To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8 years. Methods We used data from 167 mother-child pairs recruited during pregnancy (2003–2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16 ± 3 weeks of gestation and childhood sera at ages 3 and 8 years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5 years and Wide Range Achievement Test-4 at age 8 years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. Results Median serum PFASs concentrations were PFOS > PFOA > PFHxS > PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8 years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (β: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (β: 4.2, 95% CI: 0.5, 8.0) at age 8 years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (β: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (β: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (β: 5.9, 95% CI: 1.5, 10.2) at age 5 years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (β: 5.8, 95% CI: 0.8, 10.7) at age 8 years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5 years, but not at age 8 years; 3-year PFOS and PFNA were positively associated with reading scores at age 5 years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills. Conclusion Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children's reading skills at ages 5 and 8 years, but no association was found between serum PFHxS and reading skills. [ABSTRACT FROM AUTHOR]

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β=4.6, 95% CI 0.5, 8.7) and BDE-153 (β=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function. [ABSTRACT FROM AUTHOR]

Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16 ± 3 weeks of gestation and during childhood at 1, 2, 3, 5, and 8 years. We assessed children's attention and impulse control using the Conners' Continuous Performance Test-Second Edition (CPT-II) at 8 years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3 years: β = 4.0 [95% CI: − 2.4, 10.5]; at 5 years: β = 4.6 [95% CI: − 2.8, 12.0]; at 8 years: β = 4.1 [95% CI: − 3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: β = 15.0 milliseconds (ms) [95% CI: − 15.8, 45.8]; 5 years: β = 20.6 ms [95% CI: − 20.8, 61.9]; 8 years: β = 28.6 ms [95% CI: − 12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d′), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8 year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research. [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]

Background Early life BPA exposure could affect neurobehavior, but few studies have investigated whether there are developmental periods when the fetus or child is more vulnerable to these potential effects. Objectives We explored windows of vulnerability to BPA exposure in a multiethnic cohort of 228 mothers and their children from Cincinnati, Ohio. Methods We measured urinary BPA concentrations at up to two prenatal and six postnatal time points from the 2nd trimester of pregnancy until the child was age 8 years. At age 8 years, we administered the Behavioral Assessment System for Children-2 (BASC-2), Behavior Rating Inventory of Executive Function, and Wechsler Intelligence Scale for Children-IV. We estimated covariate-adjusted differences in composite scores from each instrument using a multiple informant model designed to identify heightened windows of vulnerability. Results Among all children, there was not strong evidence that the associations between BPA and neurobehavior varied by the timing of exposure (Visit x BPA p -values ≥ 0.16). However, child sex modified the associations of repeated BPA measures with BASC-2 scores (Visit x Sex x BPA p -values = 0.02–0.23). For example, each 10-fold increase in prenatal BPA was associated with more externalizing behaviors in girls (β = 6.2, 95% CI: 0.8, 11.6), but not boys (β = − 0.8, 95% CI: − 5.0, 3.4). In contrast, a 10-fold increase in 8-year BPA was associated with more externalizing behaviors in boys (β = 3.9, 95% CI: 0.6, 7.2), but not girls (β = 0.3, 95% CI: − 3.5, 4.1). Conclusions We found that sex-dependent associations between BPA and child neurobehavior may depend on the timing of BPA exposure. [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]

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]