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Background: Evaluating individual health outcomes does not capture co-morbidities children experience. Purpose: We aimed to describe profiles of child neurodevelopment and anthropometry and identify their predictors. Methods: Using data from 501 mother-child pairs (age 3-years) in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a prospective cohort study, we developed phenotypic profiles by applying latent profile analysis to twelve neurodevelopmental and anthropometric traits. Using multinomial regression, we evaluated odds of phenotypic profiles based on maternal, sociodemographic, and child level characteristics. Results: For neurodevelopmental outcomes, we identified three profiles characterized by Non-optimal (9%), Typical (49%), and Optimal neurodevelopment (42%). For anthropometric outcomes, we observed three profiles of Low (12%), Average (61%), and Excess Adiposity (27%). When examining joint profiles, few children had both Non-optimal neurodevelopment and Excess Adiposity (2%). Lower household income, lower birthweight, younger gestational age, decreased caregiving environment, greater maternal depressive symptoms, and male sex were associated with increased odds of being in the Non-optimal neurodevelopment profile. Higher pre-pregnancy body mass index was associated with increased odds of being in the Excess Adiposity profile. Conclusions: Phenotypic profiles of child neurodevelopment and adiposity were associated with maternal, sociodemographic, and child level characteristics. Few children had both non-optimal neurodevelopment and excess adiposity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. OBJECTIVES: We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. METHODS: We used data from the Maternal–Infant Research on Environmental Chemicals study (2008–2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3–4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between log2-transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. RESULTS: Third-trimester BLLs were associated with increased SRS-2 scores [β[sub 푎푑푗] = 3.3; 95% confidence interval (CI): 1.1, 5.5] among participants with low (<10th percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (β[sub 푎푑푗] = -0.3; 95% CI: -1.2, 0.5) among those in the middle category (≥10th and <80th percentiles) (푝-interaction <0.001). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP (β[sub 푎푑푗]= 0.9; 95% CI: -1.2, 3.1) than those without the T allele (β[sub 푎푑푗] = -0.3; 95% CI: -1.3, 0.7), but the difference was not statistically significant (푝-interaction = 0.28). DISCUSSION: Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. [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: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure–response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/ Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%–148% and 4%–94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glyphosate is one of the most heavily used pesticides in the world, but little is known about sources of glyphosate exposure in pregnant people living in agricultural regions. OBJECTIVE: Our objective was to evaluate glyphosate exposure during pregnancy in relation to residential proximity to agriculture as well as agricultural spray season. METHODS: We quantified glyphosate concentrations in 453 urine samples collected biweekly from a cohort of 40 pregnant people in southern Idaho from February through December 2021. We estimated each participant’s glyphosate exposure as the geometric mean (GM) of glyphosate concentrations measured in all samples (average 푛= 11 samples/participant), as well as the GM of samples collected during the pesticide “spray season” (defined as those collected 1 May–15 August; average 푛= 5 samples/participant) and the “nonspray season” (defined as those collected before 1 May or after 15 August; average 푛= 6 samples/participant). We defined participants who resided < 0.5 km from an actively cultivated agriculture field to live “near fields” and those residing = 0.5 km from an agricultural field to live “far from fields” (푛= 22 and 18, respectively). RESULTS: Among participants living near fields, urinary glyphosate was detected more frequently and at significantly increased GM concentrations during the spray season in comparison with the nonspray season (81% vs. 55%; 0.228 μg/L vs. 0.150 μg/L, 푝 < 0.001). In contrast, among participants who lived far from fields, neither glyphosate detection frequency nor GMs differed in the spray vs nonspray season (66% vs. 64%; 0.154 μg/L vs. 0.165 μg/L, 푝= 0.45). Concentrations did not differ by residential proximity to fields during the nonspray season (0.154 μg/L vs. 0.165μg/L, for near vs. far, 푝= 0.53). DISCUSSION: Pregnant people living near agriculture fields had significantly increased urinary glyphosate concentrations during the agricultural spray season than during the nonspray season. They also had significantly higher urinary glyphosate concentrations during the spray season than those who lived far from agricultural fields at any time of year, but concentrations did not differ during the nonspray season. These findings suggest that agricultural glyphosate spray is a source of exposure for people living near fields. [ABSTRACT FROM AUTHOR]

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

BACKGROUND: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. OBJECTIVES: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn on the risk of developing gestational hypertension and preeclampsia in a cohort of Canadian women. METHODS: Metal concentrations were analyzed in first and third trimester maternal blood (푛=1,560). We measured blood pressure after 20 wk gestation to diagnose gestational hypertension, whereas proteinuria and other complications defined preeclampsia. We estimated individual and independent (adjusted for coexposure) relative risks (RRs) for each doubling of metal concentrations and examined interactions between toxic metals and Mn. We used quantile g-computation to estimate the joint effect of trimester-specific exposures. RESULTS: Each doubling of third trimester Pb (RR = 1.54; 95% CI: 1.06, 2.22) and first trimester blood As (RR = 1.25; 95% CI: 1.01, 1.58) was independently associated with a higher risk of developing preeclampsia. First trimester blood As (RR = 3.40; 95% CI: 1.40, 8.28) and Mn (RR = 0.63; 95% CI: 0.42, 0.94) concentrations were associated with a higher and lower risk, respectively, of developing gestational hypertension. Mn modified the association with As such that the deleterious association with As was stronger at lower concentrations of Mn. First trimester urinary dimethylarsinic acid concentrations were not associated with gestational hypertension (RR = 1.31; 95% CI: 0.60, 2.85) or preeclampsia (RR = 0.92; 95% CI: 0.68, 1.24). We did not observe overall joint effects for blood metals. DISCUSSION: Our results confirm that even low blood Pb concentrations are a risk factor for preeclampsia. Women with higher blood As concentrations combined with lower Mn in early pregnancy were more likely to develop gestational hypertension. These pregnancy complications impact maternal and neonatal health. Understanding the contribution of toxic metals and Mn is of public health importance. [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]

Objective: The study aimed to identify periods of heightened susceptibility to the effects of pre- and postnatal secondhand tobacco smoke (SHS) exposure on body composition at age 12 years.Methods: The study used data from 217 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort in Cincinnati, Ohio. Using multiple informant models, the study estimated associations of maternal serum cotinine (16 and 26 weeks of pregnancy) and child serum cotinine concentrations (at age 12, 24, 36, and 48 months) with measures of body composition obtained with anthropometry and dual-energy x-ray absorptiometry at 12 years. We examined whether there were differences between these associations for pre- and postnatal exposure periods and potential effect measure modification by sex.Results: Postnatal cotinine concentrations were associated with higher weight, BMI, body fat and lean mass, waist circumference, and visceral, android, and gynoid fat. Each 10-fold increase in postnatal cotinine was associated with 76% increased risk of overweight or obesity (95% CI: 1.13-2.75). Associations between prenatal concentrations and measures of body composition at 12 years were generally null.Conclusions: Postnatal exposure to SHS may increase adolescent adiposity and lean mass. Future studies should determine whether early-life exposures to SHS are associated with other cardiometabolic risk markers. [ABSTRACT FROM AUTHOR]

BACKGROUND: No safe level of lead in blood has been identified. Blood lead testing is required for children on Medicaid, but it is at the discretion of providers and parents for others. Elevated blood lead levels (EBLLs) cannot be identified in children who are not tested. OBJECTIVES: The aims of this research were to identify determinants of lead testing and EBLLs among North Carolina children and estimate the number of additional children with EBLLs among those not tested. METHODS: We linked geocoded North Carolina birth certificates from 2011–2016 to 2010 U.S. Census data and North Carolina blood lead test results from 2011–2018. We estimated the probability of being screened for lead and created inverse probability (IP) of testing weights. We evaluated the risk of an EBLL of =3 µg/dL at <30 months of age, conditional on characteristics at birth, using generalized linear models and then applied IP weights to account for missing blood lead results among unscreened children. We estimated the number of additional children with EBLLs of all North Carolina children using the IP-weighted population and bootstrapping to produce 95% credible intervals (CrI). RESULTS: Mothers of the 63.5% of children (402,002 of 633,159) linked to a blood lead test result were disproportionately young, Hispanic, Black, American Indian, or on Medicaid. In full models, maternal age =20 y [risk ratio (RR)=1.10; 95% confidence interval (CI): 1.13, 1.20] or smoking (RR=1.14; 95% CI: 1.12, 1.17); proximity to a major roadway (RR=1.10; 95% CI: 1.05, 1.15); proximity to a lead-releasing Toxics Release Inventory site (RR=1.08; 95% CI: 1.03, 1.14) or a National Emissions Inventory site (RR=1.11; 95% CI: 1.07, 1.14); and living in neighborhoods with more housing built before 1950 (RR=1.10; 95% CI: 1.05, 1.14) or before 1940 (RR=1.18; 95% CI: 1.11, 1.25) or more vacant housing (RR=1.14; 95% CI: 1.11, 1.17) were associated with an increased risk of EBLL, whereas overlap with a public water service system was associated with a decreased risk of EBLL (RR=0.85; 95% CI: 0.83, 0.87). Children of Black mothers were no more likely than children of White mothers to have EBLLs (RR=0.98; 95% CI: 0.96, 1.01). Complete blood lead screening in 2011–2018 may have identified an additional 17,543 (95% CrI: 17,462, 17,650) children with EBLLs =3 µg/dL. DISCUSSION: Our results indicate that current North Carolina lead screening strategies fail to identify over 30% (17,543 of 57,398) of children with subclinical lead poisoning and that accounting for characteristics at birth alters the conclusions about racial disparities in children’s EBLLs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Developmental exposure to air pollution is associated with diminished cognitive abilities in observational studies, but no randomized controlled trial has examined the effect of reducing air pollution on cognition in children. OBJECTIVES: We sought to quantify the impact of reducing exposure to particulate matter (PM) during pregnancy on children’s cognitive performance at 4 y of age. METHODS: In this single-blind, parallel-group, randomized controlled trial in Ulaanbaatar, Mongolia, we randomly assigned 540 nonsmoking pregnant women (268 intervention and 272 control) to receive 1–2 portable high-efficiency particulate air (HEPA) filter air cleaners or no air cleaners. The air cleaners were used from a median of 11 wk gestation until the end of pregnancy. The primary outcome was full-scale intelligence quotient (FSIQ) assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) when children were a median of 48 months old. We imputed missing outcome data using multiple imputation with chained equations, and our primary analysis was by intention to treat. RESULTS: After excluding known miscarriages, stillbirths, neonatal deaths, and medical conditions that impeded cognitive testing and imputation, 475 (233 control and 242 intervention) children were included in our analyses. In an unadjusted analysis, the mean FSIQ of children who were randomly assigned to the intervention group was 2.5 points [95% confidence interval (CI): -0.4, 5.4 points] higher than that of children in the control group. After adjustment to account for an imbalance in preterm birth between groups, the effect estimate increased to 2.8 points (95% CI: -0.1, 5.7). CONCLUSIONS: Reducing PM air pollution during pregnancy may improve cognitive performance in childhood. [ABSTRACT FROM AUTHOR]

BACKGROUND: The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. METHODS: We enrolled 2,001 women >18 years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3–4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale–II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 푇-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS: Mean total SRS 푇-score was 45.3 (SD = 6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3- carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS 푇-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS 푇-scores. Associations were consistently and significantly stronger in boys (ßMBP = 1.0; 95% CI: 0.4, 1.6; n = 252) compared with girls (ßMBP = 0.1; 95% CI: -0.6, 0.7; n = 258) and among children who had lower prenatal folic acid supplementation (<400 µg/d) (bMBP = 1:3; 95% CI: 0.4, 2.3; n = 59) compared with those who had adequate folic acid supplementation (=400 µg/d) (ßMBP = 0:4; 95% CI: -0:1, 0.8; n = 451). CONCLUSIONS: Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. [ABSTRACT FROM AUTHOR]

Objective: Adipocytokines are markers of fetal metabolism, but their association with childhood growth is unclear. This study examined associations of neonatal adipocytokines with longitudinal childhood adiposity measures in a prospective cohort of pregnant women and their children.Methods: Leptin and adiponectin concentrations at delivery and children's BMI z scores between age 4 weeks and 8 years were measured. Differences in BMI z scores and rates of BMI z score change by leptin (n = 257) and adiponectin (n = 271) terciles were estimated.Results: Children in the middle (mean difference: 0.2; 95% CI: -0.1 to 0.4) and highest (0.4; 95% CI: 0.1 to 0.6) leptin terciles had greater BMI z scores than children in the lowest tercile. Associations were null after adjustment for birth weight z score. Children in the lowest adiponectin tercile had greater gains in BMI z score (change per year: 0.10; 95% CI: 0.08 to 0.13) than children in the middle (0.07; 95% CI: 0.04 to 0.09) and highest terciles (0.04; 95% CI: -0.01 to 0.05) (adiponectin × age interaction P < 0.001).Conclusions: Lower adiponectin levels were associated with increased rates of BMI gains in the first 8 years of life. Though leptin was positively associated with BMI, this association may be confounded by birth weight. [ABSTRACT FROM AUTHOR]

Background: Mercury is toxic to the developing brain, but the lowest concentration associated with the development of behavior problems is unclear. The purpose of this study was to examine the association between very low-level mercury exposure during fetal development and behavior problems in children.Methods: We used data from 389 mothers and children in a prospective pregnancy and birth cohort study. We defined mean prenatal mercury concentration as the mean of total whole blood mercury concentrations in maternal samples collected at 16- and 26-weeks of gestation, delivery, and neonatal cord blood samples. We assessed parent-reported child behavior up to five times from two to 8 years of age using the Behavioral Assessment System for Children (BASC-2). At 8 years of age, we assessed self-reported child anxiety using the Spence Children's Anxiety Scale (SCAS). We used multiple linear mixed models and linear regression models to estimate the association between mean prenatal mercury concentrations and child behavior and anxiety, respectively.Results: The median prenatal total blood mercury concentrations was 0.67 μg/L. Overall, we did not find statistically significant associations between mean prenatal mercury concentrations and behavior problems scores, but a 2-fold increase in mercury concentrations at 16-weeks gestation was associated with 0.83 point (95% CI: 0.05, 1.62) higher BASC-2 anxiety scores. Maternal and cord blood mercury concentrations at delivery were associated with parent-reported anxiety at 8 years.Conclusion: We found limited evidence of an association between very-low level prenatal mercury exposure and behaviors in children, with an exception of anxiety. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fluoride exposures have not been established for pregnant women who live in regions with and without community water fluoridation. OBJECTIVE: Our aim was to measure urinary fluoride levels during pregnancy. We also assessed the contribution of drinking-water and tea consumption habits to maternal urinary fluoride (MUF) concentrations and evaluated the impact of various dilution correction standards, including adjustment for urinary creatinine and specific gravity (SG). METHODS: We measured MUF concentrations in spot samples collected in each trimester of pregnancy from 1,566 pregnant women in the Maternal- Infant Research on Environmental Chemicals cohort. We calculated intraclass correlation coefficients (ICCs) to assess variability in MUF concentrations across pregnancy. We used regression analyses to estimate associations between MUF levels, tea consumption, and water fluoride concentrations as measured by water treatment plants. RESULTS: Creatinine-adjusted MUF values (mean±SD; milligrams per liter) were almost two times higher for pregnant women living in fluoridated regions (0.87±0.50) compared with nonfluoridated regions (0.46±0.34; p<0.001). MUF values tended to increase over the course of pregnancy using both unadjusted values and adjusted values. Reproducibility of the unadjusted and adjusted MUF values was modest (ICC range=0.37-0.40). The municipal water fluoride level was positively associated with creatinine-adjusted MUF (B=0.52, 95% CI: 0.46, 0.57), accounting for 24% of the variance after controlling for covariates. Higher MUF concentrations correlated with numbers of cups of black (r=0.31-0.32 but not green tea (r=0.04-0.06). Urinary creatinine and SG correction methods were highly correlated (r=0.91) and were interchangeable in models examining predictors of MUF. CONCLUSION: Community water fluoridation is a major source of fluoride exposure for pregnant women living in Canada. Urinary dilution correction with creatinine and SG were shown to be interchangeable for our sample of pregnant women. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to triclosan, an endocrine disrupting chemical, may affect thyroid hormone homeostasis and adversely affect neurodevelopment. OBJECTIVE: Using a longitudinal pregnancy and birth cohort, we investigated associations between triclosan exposures during different time windows, and cognitive test scores at 8 y of age in 198 children from the HOME Study. METHODS: We quantified triclosan in urine samples from mother-child pairs up to nine times between the second trimester of gestation and 8 y of age. The Wechsler Intelligence Scale for Children-IV [i.e., Full-Scale Intelligence Quotient (IQ)] assessment was administered to HOME Study children at 8 y of age. We estimated covariate-adjusted triclosan-IQ associations at each visit. We also tested whether associations between triclosan concentrations and cognitive test scores varied among exposure at different time periods. RESULTS: Full-Scale IQ was not significantly associated with urinary triclosan concentrations during gestation or childhood but was significantly associated with a 10-fold increase in maternal urinary triclosan concentration at delivery [-4:5 points (95% CI: -7:0, -2:0)]. Perceptual Reasoning Index (PRI) scores were significantly decreased in association with urinary triclosan concentrations at delivery and at 2 y of age. Associations between repeated triclosan concentrations and cognitive test scores significantly varied among exposure at different time periods for Full-Scale IQ, PRI, Verbal Comprehension Index, and Working Memory (triclosan-visit interaction p=0:04). CONCLUSION: Urinary triclosan concentrations at delivery, but not during mid to late pregnancy and childhood, were associated with significantly lower children's cognitive test scores at 8 y of age in this cohort of U.S. children. [ABSTRACT FROM AUTHOR]

Introduction Maternal exposure to tobacco smoke is associated with shortened breastfeeding duration, but few studies have examined the effects on breastfeeding outcomes of low level exposures to other toxic chemicals. Moreover, it is unclear if passive smoking is associated with duration of breastfeeding. Our objective was therefore to examine the effect of low-level prenatal exposures to common environmental toxins (tobacco smoke, lead, and phthalates) on breastfeeding exclusivity and duration. Methods We conducted an analysis of data from the Health Outcomes and Measures of the Environment (HOME) Study. Serum and urine samples were collected at approximately 16 and 26 weeks gestation and at delivery from 373 women; 302 breastfed their infants. Maternal infant feeding interviews were conducted a maximum of eight times through 30 months postpartum. The main predictor variables for this study were gestational exposures to tobacco smoke (measured by serum cotinine), lead, and phthalates. Passive smoke exposure was defined as cotinine levels of 0.015-3.0 μg/mL. Primary outcomes were duration of any and exclusive breastfeeding. Results Serum cotinine concentrations were negatively associated with the duration of any breastfeeding (29.9 weeks unexposed vs. 24.9 weeks with passive exposure, p = 0.04; and 22.4 weeks with active exposure, p = 0.12; p = 0.03 for linear trend), but not duration of exclusive breastfeeding. Prenatal levels of blood lead and urinary phthalate metabolites were not significantly associated with duration of any or exclusive breastfeeding. Conclusions Passive exposure to tobacco smoke during pregnancy was associated with shortened duration of any breastfeeding. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are exposed to a mixture of endocrine disrupting chemicals (EDCs). Gestational EDC exposures may be associated with changes in fetal growth that elevates the risk for poor health later in life, but few studies have examined the health effects of simultaneous exposure to multiple chemicals. This study aimed to examine the association of gestational exposure to five chemical classes of potential EDCs: phthalates and bisphenol A, perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) with infant birth weight.Methods: Using data from the Health Outcomes and Measures of Environment (HOME) Study, we examined 272 pregnant women enrolled between 2003-2006. EDC concentrations were quantified in blood and urine samples collected at 16 and 26 weeks gestation. We used Bayesian Hierarchical Linear Models (BHLM) to examine the associations between newborn birth weight and 53 EDCs, 2 organochlorine pesticides (OPPs) and 2 heavy metals.Results: For a 10-fold increase in chemical concentration, the mean differences in birth weights (95% credible intervals (CI)) were 1 g (-20, 23) for phthalates, -11 g (-52, 34) for PFAS, 0.2 g (-9, 10) for PCBs, -4 g (-30, 22) for PBDEs, and 7 g (-25, 40) for OCPs.Conclusion: Gestational exposure to phthalates, PFAS, PCBs, PBDEs, OCPs or OPPs had null or small associations with birth weight. Gestational OPP, Pb, and PFAS exposures were most strongly associated with lower birth weight. [ABSTRACT FROM AUTHOR]

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑ DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 [ABSTRACT FROM AUTHOR]

BACKGROUND: In the United States, one in six children are affected by neurodevelopmental disorders, and polybrominated diphenyl ethers (PBDEs) in flame-retardant chemicals are measured ubiquitously in children. OBJECTIVE: We conducted a systematic a systematic review regarding developmental exposure to PBDEs and intelligence or Attention Deficit/ Hyperactivity Disorder (ADHD) and attention-related behavioral conditions in humans. METHODS: We searched articles published up to 26 September 2016, and included original studies that quantified exposures to PBDEs incurred any time in proximity to conception or during in utero, perinatal, or childhood time periods. We evaluated the risk of bias of individual studies and the overall quality and strength of the evidence according to the Navigation Guide systematic review methodology. We established criteria in advance to identify studies that could be combined using random effects meta-analyses (DerSimonian-Laird method). RESULTS: Fifteen studies met the inclusion criteria; 10 studies met the criteria for intelligence and nine for attention-related problems. We rated studies generally with "low" to "probably low" risk of bias and rated the overall body of evidence as "moderate" quality with "sufficient" evidence for an association between Intelligence Quotient (IQ) and PBDEs. Our meta-analysis of four studies estimated a 10-fold increase (in other words, times 10) in PBDE exposure associated with a decrement of 3.70 IQ points (95% confidence interval: 0.83, 6.56). We concluded the body of evidence was of "moderate" quality for ADHD with "limited" evidence for an association with PBDEs, based on the heterogeneity of association estimates reported by a small number of studies and the fact that chance, bias, and confounding could not be ruled out with reasonable confidence. CONCLUSION: We concluded there was sufficient evidence supporting an association between developmental PBDE exposure and reduced IQ. Preventing developmental exposure to PBDEs could help prevent loss of human intelligence. [ABSTRACT FROM AUTHOR]

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

BACKGROUND: Prenatal polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) exposures may influence children's neurodevelopment. OBJECTIVE: We examined the association of prenatal PBDE and PCB exposures with children's reading skills at ages 5 and 8 years, Full-Scale Intelligence Quotient (FSIQ), and externalizing behavior problems at age 8 years. METHODS: From 239 mother-child pairs recruited (2003-2006) in Cincinnati, Ohio, we measured maternal serum PBDE and PCB concentrations, assessed child's reading skills using the Woodcock-Johnson Tests of Achievement III (WJ-III) at age 5 years and the Wide Range Achievement Test-4 (WRAT-4) at age 8 years, tested FSIQ using the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing behavior problems using the Behavioral Assessment System for Children-2 (BASC-2) at age 8 years. We used multiple linear regression to examine the association of prenatal PBDE and PCB concentrations and reading, FSIQ, and externalizing behavior problems after adjusting for covariates. RESULTS: An increase of Sum4PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) by 10 times was not significantly associated with reading scores at age 5 years at the p = 0.05 level but was inversely associated with Reading Composite scores (β: -6.2, 95% CI: -11.7, -0.6) and FSIQ (β: -5.3, 95% CI: -10.6, -0.02) at age 8 years; it was positively associated with the score for externalizing behavior problems (β: 3.5, 95% CI: -0.1, 7.2) at age 8 years. Prenatal Sum4PCBs (PCB-118, -153, -138-158, and -180) was not significantly associated with a child's reading skills, FSIQ, and externalizing behavior problems. Conclusion: Prenatal PBDE concentration was inversely associated with reading skills and FSIQ and positively associated with externalizing behavior problems at age 8 years. No significant associations were found in prenatal PCB concentration. CITATION: Zhang H, Yolton K, Webster GM, Sjödin A, Calafat AM, Dietrich KN, Xu Y, Xie C, Braun JM, Lanphear BP, Chen A. 2017. Prenatal PBDE and PCB exposures and reading, cognition, and externalizing behavior in children. Environ Health Perspect 125:746-752; http://dx.doi.org/10.1289/EHP478 [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposure to endocrine disruptors has been associated with increased risk of childhood obesity. However, epidemiologic studies on polybrominated diphenyl ethers (PBDEs) are limited despite animal studies indicating PBDEs' potential role as an obesogen. OBJECTIVES: We investigated whether maternal concentrations of BDEs 28, 47, 99, 100, 153, and XPBDEs during pregnancy were associated with anthropometric measures in children aged 1-8 years. METHODS: We examined 318 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort enrolled from 2003 through 2006 (Cincinnati, OH). Serum PBDEs were measured at 16 ± 3 weeks gestation. We measured child height (1-8 years), weight (1-8 years), body mass index (BMI) (2-8 years), waist circumference (4-8 years), and body fat (8 years). To account for repeated measures, we used linear mixed models and generalized estimating equations to estimate associations between maternal PBDEs and child anthropometric measures. RESULTS: We found no statistically significant associations between prenatal PBDEs and height or weight z-score. A 10-fold increase in maternal serum BDE-153 was associated with lower BMI z-score (β = -0.36; 95% CI: -0.60, -0.13) at 2-8 years, smaller waist circumference (P = -1.81 cm; 95% CI: -3.13, -0.50) at 4-8 years, and lower percent body fat (β = -2.37%; 95% CI: -4.21, -0.53) at 8 years. A decrease in waist circumference at 4-8 years was observed with a 10-fold increase in BDE-100 (β = -1.50 cm; 95% CI: -2.93, -0.08) and ΣPBDEs (β = -1.57 cm; 95% CI:-3.11,-0.02). CONCLUSIONS: Reverse causality may have resulted in prenatal PBDEs, particularly BDE-153, and decreased BMI, waist circumference, and body fat. CITATION: Vuong AM, Braun JM, Sjödin A, Webster GM, Yolton K, Lanphear BP, Chen A. 2016. Prenatal polybrominated diphenyl ether exposure and body mass index in children up to 8 years of age. Environ Health Perspect 124:1891-1897; http://dx.doi.org/10.1289/EHP139 [ABSTRACT FROM AUTHOR]

Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socio-economic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound. [ABSTRACT FROM AUTHOR]

Background: Phthalates, used in a variety of consumer products, are a group of chemicals that are ubiquitous in the environment, and their metabolites are detectable in most humans. Some phthalates have anti-androgenic properties; a prior study reported an association between gestational exposure to phthalates and reduced masculine behaviors in preschool boys.Methods: Concentrations of 9 phthalate metabolites were measured in urine collected at 16 and 26 weeks' gestation from pregnant women enrolled in the HOME Study, a prospective pregnancy and birth cohort. Measures of gender-related play were collected at 8 years of age, including the Gender Identity Questionnaire (GIQ) completed by mothers, and the Playmate and Play Style Preferences Structured Interview (PPPSI) completed by children. We examined these measures as continuous variables using both bivariate and multivariable approaches with adjustment for covariates. Additional analyses included logistic regression of GIQ and PPPSI scores dichotomized by sex at the lower 25th percentile, indicating the least typical behavior.Results: Mothers' phthalate metabolite concentrations during pregnancy were similar to the reported national average among US women. All children scored within a typical range on both measures of gender-related play behavior. No statistically significant associations were found between averaged maternal phthalate metabolite concentrations and continuous PPPSI scores or any GIQ scores. For the dichotomized PPPSI; higher maternal monoethyl phthalate (MEP) concentrations were associated with more typical play behaviors for females (OR = 0.70, CI = 0.51-0.97). In contrast, higher maternal mono-isobutyl phthalate (MiBP) concentrations were associated with higher odds of membership in the least typical play behaviors group for males (OR = 1.69, CI = 1.00-2.86).Conclusions: In this sample of typically developing children, higher maternal urinary MEP concentrations during pregnancy were associated with more typical gender-related play behaviors in both males and females, and increased urinary MiBP concentrations were associated with less masculine gender-related play behaviors in males. [ABSTRACT FROM AUTHOR]

BACKGROUND: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. OBJECTIVES: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). METHODS: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. RESULTS: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1[sub 192RR] genotype, ΣDAP and ΣDMP were negatively associated with length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.5 cm; 95% CI:-0.9, -0.1). CONCLUSIONS: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1[sub 192RR] genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluoroalkyl acids (PFASs) are suspected thyroid toxicants, but results from epidemiological studies are inconsistent. OBJECTIVES: We examined associations between serum PFASs and thyroid hormones (THs) in a representative, cross-sectional sample of U.S. adults. We hypothesized that people with high thyroid peroxidase antibodies and low iodine would be more susceptible to PFAS-induced thyroid disruption. METHODS: Our sample included 1,525 adults (≤ 18 years) from the 2007-2008 NHANES study with available serum PFASs and THs. We examined associations between four serum PFASs [perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA), and perfluorooctane sulfonate (PFOS)], and serum THs [free triiodothyronine (fT3), free thyroxine (fT4), fT3/fT4, thyroid-stimulating hormone (TSH), total T3 (TT3), and total T4 (TT4)] using multivariable linear regression. We stratified subjects into four groups by two indicators of thyroid "stress": thyroid peroxidase antibody (TPOAb ≥ 9 IU/mL) and iodine status (< 100 µg/L urine). RESULTS: Of 1,525 participants, 400 (26%) had low iodine only (T0I1), 87 (6%) had high TPOAb only (T1I0), and 26 (2%) had both high TPOAb and low iodine (T1I1). In general, associations were similar among participants in the groups with neither (T0I0) or only one thyroid stressor (T0I1 or T1I0), suggesting that PFAS-TH associations were not modified by high TPOAb or low iodine alone. However, PFHxS and PFOS were negatively associated (p < 0.05) with fT4, and all four PFASs were positively associated (p < 0.05) with fT3, fT3/fT4, TSH, and TT3 in the group with joint exposure to high TPOAb and low iodine (T1I1). CONCLUSIONS: We found evidence of PFAS-associated thyroid disruption in a subset of U.S. adults with high TPOAb (a marker of autoimmune hypothyroidism) and low iodine status, who may represent a vulnerable subgroup. However, the small sample size, cross-sectional design, and possibility of reverse causation are limitations of this work. [ABSTRACT FROM AUTHOR]

BACKGROUND: Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001. Objectives: We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. METHODS: Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (Σ) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype. RESULTS: There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. CONCLUSIONS: Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure. [ABSTRACT FROM AUTHOR]

The broad-spectrum herbicide glyphosate (common trade name "Roundup") was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization's International Agency for Research on Cancer recently concluded that glyphosate is "probably carcinogenic to humans." In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants. OBJECTIVES: We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera. METHODS: We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ±3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256). RESULTS: Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT4), respectively. Both congeners were also positively associated with maternal free thyroxine (FT4). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT3 and FT3). A 10-fold increase in BDE-28 was associated with elevated FT3 concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum. CONCLUSIONS: These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T4 and T3 during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Exposure to phthalates, a class of endocrine disrupting chemicals, is ubiquitous. We examined the association of urinary phthalate metabolite concentrations during pregnancy with maternal blood pressure and risk of pregnancy-induced hypertensive diseases.Methods: We used data from the Health Outcomes and Measures of the Environment Study, a prospective birth cohort of low-risk pregnant women recruited between March 2003 and January 2006. We analyzed maternal urine samples collected at 16 and 26 weeks gestation for 9 phthalate monoester metabolites reflecting exposure to 6 phthalate diesters. Outcomes included maternal blood pressure at <20 and ≥ 20 weeks gestation and pregnancy induced hypertensive diseases (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome).Results: Data were available for 369 women who gave birth to singleton, live-born infants without congenital anomalies. Of the phthalate metabolites evaluated, only mono-benzyl phthalate (MBzP) concentrations were significantly associated with maternal diastolic blood pressure at <20 weeks gestation. Women in the third MBzP tercile at 16 weeks gestation had diastolic blood pressure 2.2 (95% CI: 0.5-3.9) mm Hg higher at <20 weeks gestation and 2.8 (95% CI: 0.9-4.7) mm Hg higher at ≥ 20 weeks gestation compared to women in the first tercile. Compared to women in the first tercile, women in the top MBzP tercile at 16 weeks had an increased risk of developing pregnancy-induced hypertensive diseases (RR = 2.92, 95 % CI 1.15-7.41, p-value for trend = 0.01). MBzP concentrations at 26 weeks gestation were not as strongly associated with blood pressure at ≥ 20 weeks gestation or risk of pregnancy-induced hypertensive diseases.Conclusion: This study suggests that maternal urinary MBzP concentrations may be associated with increased diastolic blood pressure and risk of pregnancy-induced hypertensive diseases. [ABSTRACT FROM AUTHOR]

Background: Early-life exposure to bisphenol A (BPA) may increase childhood obesity risk, but few prospective epidemiological studies have investigated this relationship. Objective: We sought to determine whether early-life exposure to BPA was associated with increased body mass index (BMI) at 2–5 years of age in 297 mother–child pairs from Cincinnati, Ohio (HOME Study). Methods: Urinary BPA concentrations were measured in samples collected from pregnant women during the second and third trimesters and their children at 1 and 2 years of age. BMI z-scores were calculated from weight/height measures conducted annually from 2 through 5 years of age. We used linear mixed models to estimate BMI differences or trajectories with increasing creatinine-normalized BPA concentrations. Results: After confounder adjustment, each 10-fold increase in prenatal (β = –0.1; 95% CI: –0.5, 0.3) or early-childhood (β = –0.2; 95% CI: –0.6, 0.1) BPA concentrations was associated with a modest and nonsignificant reduction in child BMI. These inverse associations were suggestively stronger in girls than in boys [prenatal effect measure modification (EMM) p-value = 0.30, early-childhood EMM p-value = 0.05], but sex-specific associations were imprecise. Children in the highest early-childhood BPA tercile had lower BMI at 2 years (difference = –0.3; 95% CI: –0.6, 0.0) and larger increases in their BMI slope from 2 through 5 years (BMI increase per year = 0.12; 95% CI: 0.07, 0.18) than children in the lowest tercile (BMI increase per year = 0.07; 95% CI: 0.01, 0.13). All associations were attenuated without creatinine normalization. Conclusions: Prenatal and early-childhood BPA exposures were not associated with increased BMI at 2–5 years of age, but higher early-childhood BPA exposures were associated with accelerated growth during this period. [ABSTRACT FROM AUTHOR]

Prenatal multivitamin/folic acid supplement use may reduce the risk of autism spectrum disorders. We investigated whether 2nd trimester prenatal vitamin use and maternal whole blood folate (WBF) concentrations were associated with Social Responsiveness Scale (SRS) scores at 4-5 years of age in a prospective cohort of 209 mother-child pairs. After confounder adjustment, children born to women taking prenatal vitamins weekly/daily (n = 179) had lower odds of clinically elevated SRS scores (odds ratio 0.26; 95 % confidence interval 0.08, 0.89) than those who rarely/never took them (n = 30). WBF concentrations were not associated with SRS scores. The lack of association between WBF and autistic-behaviors may be due to the timing of biomarker measures relative to critical periods of brain development, confounding, or other modifying factors. [ABSTRACT FROM AUTHOR]

Background: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been widely used as flame retardants in furniture, carpet padding, car seats, and other consumer products during the past three decades. Objective: We examined whether in utero exposure to PBDEs is associated with child cognitive function and behavior in a U.S. study sample. Methods: In a prospective birth cohort, we measured maternal serum concentrations of BDE‑47 and other PBDE congeners in 309 women at 16 weeks of gestation during 2003–2006 and followed their children in Cincinnati, Ohio. We measured cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years; intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years; and children’s behaviors using the Behavioral Assessment System for Children-2 annually at ages 2–5 years. We used linear mixed models or generalized estimating equations with adjustment for potential confounders to estimate associations between these outcomes and log10-transformed PBDE concentrations. Results: The geometric mean of BDE‑47 in maternal serum (20.1 ng/g lipid) was comparable with U.S. adult national reference values. Prenatal BDE‑47 was not significantly associated with Bayley Mental or Psychomotor Development Indices at 1–3 years, but a 10-fold increase in prenatal BDE‑47 was associated with a 4.5-point decrease (95% CI: –8.8, –0.1) in Full-Scale IQ and a 3.3‑point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years. Conclusions: Prenatal exposure to PBDEs was associated with lower IQ and higher hyperactivity scores in children. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes. Objective: We examined the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birth weight. Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (&epsillon;DAP) with gestational age and birth weight. We also examined whether these associations differed according to infant PON1192 and PON1-108 genotypes. Results: Among 306 mother-infant dyads, a 10-fold increase in &epsillon;DAP concentrations was associated with a decrease in covariate-adjusted gestational age [-0.5 weeks; 95% confidence interval (CI): -0.8, -0.1] and birth weight (-151 g; CI: -287, -16); the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between &epsillon;DAP concentrations and gestational age was stronger for white (-0.7 weeks; CI: -1.1, -0.3) than for black (-0.1 weeks; 95% CI: -0.9, 0.6) newborns. In contrast, there was a greater decrease in birth weight with increasing urinary &epsillon;DAP concentrations for black (-188 g; CI: -395, 19) than for white (-118 g; CI: -296, 60) newborns. Decrements in birth weight and gestational age associated with &epsillon;DAP concentrations were greatest among infants with PON1192QR and PON-108CT genotypes. Conclusions: Prenatal urinary &epsillon;DAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and PON1192/108 genotypes. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA), an endocrine-disrupting chemical that is routinely detected in > 90% of Americans, promotes experimental asthma in mice. The association of prenatal BPA expo­sure and wheeze has not been evaluated in humans. Objective: We examined the relationship between prenatal BPA exposure and wheeze in early childhood. Methods: We measured BPA concentrations in serial maternal urine samples from a prospective birth cohort of 398 mother-infant pairs and assessed parent-reported child wheeze every 6 months for 3 years. We used generalized estimating equations with a logit link to evaluate the association of prenatal urinary BPA concentration with the dichotomous outcome wheeze (wheeze over the previous 6 months). Results: Data were available for 365 children; BPA was detected in 99% of maternal urine samples during pregnancy. In multivariable analysis, a one-unit increase in log-transformed creatinine-standardized mean prenatal urinary BPA concentration was not significantly associated with child wheeze from birth to 3 years of age, but there was an interaction of BPA concentration with time (p = 0.003). Mean prenatal BPA above versus below the median was positively associated with wheeze at 6 months of age [adjusted odds ratio (AOR) = 2.3; 95% confidence interval (CI): 1.3, 4.1] but not at 3 years (AOR = 0.6; 95% CI: 0.3, 1.1). In secondary analyses evaluating associations of each prenatal BPA concentration separately, urinary BPA concentrations measured at 16 weeks gestation were associated with wheeze (AOR = 1.2; 95% CI: 1.0, 1.5), but BPA concentrations at 26 weeks of gestation or at birth were not. Conclusions: Mean prenatal BPA was associated with increased odds of wheeze in early life, and the effect diminished over time. Evaluating exposure at each prenatal time point demonstrated an association between wheeze from 6 months to 3 years and log-transformed BPA concentration at 16 weeks gestation only [ABSTRACT FROM AUTHOR]

Background: Low-level environmental cadmium exposure in children may be associated with adverse neurodevelopmental outcomes. Objective: Our aim was to evaluate associations between urinary cadmium concentration and reported learning disability (LD), special education utilization, and attention deficit hyperactivity disorder (ADHD) in U.S. children using National Health and Nutrition Examination Survey (NHANES) data. Methods: We analyzed data from a subset of participants in NHANES (1999-2004) who were 6-15 years of age and had spot urine samples analyzed for cadmium. Outcomes were assessed by parent or proxy-respondent report. We fit multivariable-adjusted logistic regression models to estimate associations between urinary cadmium and the outcomes. Results: When we compared children in the highest quartile of urinary cadmium with those in the lowest quartile, odds ratios adjusted for several potential confounders were 3.21 [95% confidence interval (CI): 1.43, 7.17] for LD, 3.00 (95% CI: 1.12, 8.01) for special education, and 0.67 (95% CI: 0.28, 1.61) for ADHD. There were no significant interactions with sex, but associations with LD and special education were somewhat stronger in males, and the trend in the ADHD analysis was only evident among those with blood lead levels above the median. Conclusions: These findings suggest that children who have higher urinary cadmium concentrations may have increased risk of both LD and special education. Importantly, we observed these associations at exposure levels that were previously considered to be without adverse effects, and these levels are common among U.S. children. [ABSTRACT FROM AUTHOR]

CONTEXT: Most of the U.S. population is exposed to the high-production-volume chemical bisphenol A (BPA), but targetable sources of exposure remain to be determined. Animal studies and one human study suggest that BPA is a neurotoxicant. CASE PRESENTATION: A mother in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort examining prenatal and postnatal environmental toxicants and childhood health outcomes, had a urinary BPA concentration of 583 µg/g creatinine at 27 weeks of pregnancy, which was the highest concentration observed in this cohort (median, 2.0 µg/g creatinine) and the general population. We used prenatal questionnaire data and a follow-up interview to identify potential sources of exposure that included daily plastic use and consumption of canned beverages and foods. Her male infant had a normal newborn neurobehavioral assessment but presented with abnormalities at the 1-month examination that prompted physician referral. Subsequently, the child had normal neurobehavioral testing results at annual evaluations from 1 to 5 years of age. DISCUSSION: Investigations into sources of high gestational urinary BPA concentrations provide an opportunity to identify potential targets for reduction of BPA exposure. This case highlights a potential link between gestational BPA exposure and transient neurobehavioral changes that is hypothesis generating and can serve to alert researchers to potential areas for examination in future studies. RELEVANCE TO CLINICAL PRACTICE: It is important to educate health care practitioners regarding potential sources of BPA exposure and anticipatory guidance on minimization of exposures during vulnerable periods of development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goal was to test the effects of high-efficiency, particulate-arresting (HEPA) air cleaners on unscheduled asthma visits and symptoms among children with asthma exposed to secondhand smoke. METHODS: We enrolled 225 eligible children who were 6 to 12 years of age, had physician-diagnosed asthma, and were exposed to ≥5 cigarettes per day. We conducted a double-blind, randomized trial. Children were assigned randomly to receive 2 active or inactive HEPA air cleaners. RESULTS: Of 225 enrolled children, 110 (49%) were assigned to the intervention group and 115 (51%) to the control group; 215 (95%) completed the trial. During the trial, there were 42 fewer unscheduled asthma visits among children in the intervention group (18.5% [95% confidence interval: 1.25%-82.75%1; P = .043), compared with those in the control group, after adjustment for baseline differences. There was a significant difference in the reductions of levels of particles of >0.3 μm according to group assignment; there was a 25% reduction in particle levels in the intervention group, compared with a 5% reduction in the control group (P = .026). There were no significant differences in parent-reported asthma symptoms, exhaled nitric-oxide levels, air nicotine levels, or cotinine levels according to group assignment. CONCLUSIONS: These results hold promise for using HEPA air cleaners as part of a multifaceted strategy to reduce asthma morbidity, but further research is necessary before they can be recommended routinely for the medical management of asthma. [ABSTRACT FROM AUTHOR]

Background: Excess weight gain in infancy and childhood is associated with increased risk of subsequent obesity. Identifying patterns of infancy and childhood weight gain associated with subsequent obesity or overweight status could help identify children at highest risk. Thus, we examined patterns of infancy and early childhood BMI in relation to mid-childhood overweight and obesity status.Methods: In a prospective cohort of 215 children from Cincinnati, OH (born: 2003-2006), we measured weight and length or height at ages 4 weeks and 1, 2, 3, 4, 5, and 8 years. We calculated BMI z-scores using World Health Organization references. Using linear fixed effect models, we estimated mean BMI at each age and rates of change in BMI between ages 4 weeks and 5 years by children's overweight and obesity status at age 8 years, assessed with BMI z-scores or bioelectric impedance analysis (BIA).Results: Children who became overweight (BMI, n = 51 and BIA, n = 37) or obese (BMI, n = 22 and BIA, n = 29) at age 8 years had greater BMI at all ages compared to normal weightchildren. Children who were overweight had similar rates of change in BMI as children who were lean. Children who were obese had greater gains in BMI between age 4 weeks and 5 years, with the most rapid gains in the first 2 years.Conclusions: Results from this study of modest sample size, suggest that adiposity patterns in the first 5 years of life are related to subsequent childhood overweight and obesity risk. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Antibiotics are commonly administered during labor and delivery, and research has suggested that fetal exposure to antibiotics can increase risk for autism spectrum disorder (ASD). We assessed whether antibiotic exposure during labor and delivery increased the risk of ASD in the offspring. METHODS: This retrospective cohort study included everyone who delivered a live singleton-term infant in British Columbia, Canada, between April 1, 2000, and December 31, 2014. This cohort included 569 953 deliveries. To examine the association among pregnant individuals being treated for the same indication, we studied a subcohort of those who tested positive for group B Streptococcus. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios in both cohorts. A sensitivity analysis was conducted using length of first stage of labor as a proxy measure for dose to assess for a dose--response relationship. RESULTS: In this population-based study, antibiotic use during labor and delivery was not associated with an increased risk of ASD in offspring. The unadjusted and adjusted hazard ratios were 1.29 (95% confidence interval, 1.24-1.35) and 0.99 (0.94-1.04), respectively; and 1.07 (0.90-1.27) and 0.88 (0.74-1.05), respectively, in the group B Streptococcus-positive cohort. We observed no substantial difference in the association between antibiotic exposure and ASD depending on length of the first stage of labor. CONCLUSIONS: Our findings suggest that concern for ASD should not factor into the clinical decision on whether to administer antibiotics during labor and delivery. Future research is needed to examine longer durations of prenatal antibiotic exposure. [ABSTRACT FROM AUTHOR]

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

OBJECTIVE: To clarify whether persistent snoring in 2-to 3-year-olds is associated with behavioral and cognitive development, and to identify predictors of transient and persistent snoring. METHODS: Two hundred forty-nine mother/child pairs participated in a prospective birth cohort study. Based upon parental report of loud snoring ≥2 times weekly at 2 and 3 years of age, children were designated as nonsnorers, transient snorers (snored at 2 or 3 years of age, but not both), or persistent snorers (snored at both ages). We compared groups by using validated measures of behavioral and cognitive functioning. Potential predictors of snoring included child race and gender, socioeconomic status (parent education and income), birth weight, prenatal tobacco exposure (maternal serum cotinine), childhood tobacco exposure (serum cotinine), history and duration of breast milk feeding, and body mass relative to norms. RESULTS: In multivariable analyses, persistent snorers had significantly higher reported overall behavior problems, particularly hyper- activity, depression, and inattention. Nonsnorers had significantly stronger cognitive development than transient and persistent snorers in unadjusted analyses, but not after demographic adjustment. The strongest predictors of the presence and persistence of snoring were lower socioeconomic status and the absence or shorter duration of breast milk feeding. Secondary analyses suggested that race may modify the association of childhood tobacco smoke exposure and snoring. CONCLUSIONS: Persistent, loud snoring was associated with higher rates of problem behaviors. These results support routine screening and tracking of snoring, especially in children from low socioeconomic backgrounds; referral for follow-up care of persistent snoring in young children; and encouragement and facilitation of infant breastfeeding. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modified those associations. METHODS: We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). RESULTS: BPA was detected in >97% of the gestational (median: 2.0 µg/L) and childhood (median: 4.1 µg/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modified by child gender. CONCLUSIONS: In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the benefits of such reductions are unclear. [ABSTRACT FROM AUTHOR]