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Background: Chemicals found in personal care products and plastics have been associated with asthma, allergies, and lung function, but methods to address real life exposure to mixtures of these chemicals have not been applied to these associations., Methods: We quantified urinary concentrations of eleven phthalate metabolites, four parabens, and five other phenols in mothers twice during pregnancy and assessed probable asthma, aeroallergies, and lung function in their age seven children. We implemented Bayesian Profile Regression (BPR) to cluster women by their exposures to these chemicals and tested the clusters for differences in outcome measurements. We used Bayesian Kernel Machine Regression (BKMR) to fit biomarkers into one model as joint independent variables., Results: BPR clustered women into seven groups characterized by patterns of personal care product and plastic use, though there were no significant differences in outcomes across clusters. BKMR showed that monocarboxyisooctyl phthalate and 2,4-dichlorophenol were associated with probable asthma (predicted probability of probable asthma per IQR of biomarker z-score (standard deviation) = 0.08 (0.09) and 0.11 (0.12), respectively) and poorer lung function (predicted probability per IQR = -0.07 (0.05) and -0.07 (0.06), respectively), and that mono(3-carboxypropyl) phthalate and bisphenol A were associated with aeroallergies (predicted probability per IQR = 0.13 (0.09) and 0.11 (0.08), respectively). Several biomarkers demonstrated positive additive effects on other associations., Conclusions: BPR and BKMR are useful tools to evaluate associations of biomarker concentrations within a mixture of exposure and should supplement single-chemical regression models when data allow., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence., Objective: We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study., Methods: We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort ( n = 334 ). We used age-specific linear regression models and generalized estimating equation models to assess longitudinal effects and examined differences by sex., Results: Phthalate metabolites were detected in 88%-100% of samples, depending on the metabolite. Associations of phthalates with neurodevelopmental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates ( Σ LMW ) were associated with more self-reported hyperactivity [ β = 0.8 , 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in Σ LMW phthalates], attention problems ( β = 1.5 , 95% CI: 0.7, 2.2), and anxiety ( β = 0.9 , 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., β for Full-Scale IQ for boys = - 1.9 , 95% CI: - 4.1 , 0.3 and - 1.7 , 95% CI: - 3.8 , 0.3, respectively; β for girls = 1.8 , 95% CI: 0.1, 3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; p -int = 0.01 for both)., Conclusion: We found predominantly null associations of prenatal phthalates with neurodevelopment in CHAMACOS, and weak associations of Σ LMW phthalates with internalizing and externalizing behaviors in adolescence. No previous studies have examined associations of prenatal phthalate exposure with neurodevelopment into adolescence, an important time for manifestations of effects. https://doi.org/10.1289/EHP5165.

Phthalates, compounds commonly used in plastics and personal care products, have been associated with childhood obesity in cross-sectional and some longitudinal studies. Using advanced statistical methods, we characterized the heterogeneity in body mass development patterns over childhood (ages 2-14 years) and explored associations with maternal prenatal urinary concentrations of phthalates among 335 children in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study. Height and weight were measured every one to two years in this cohort, which had a high prevalence of obesity and overweight. Building upon a previous analysis that showed a positive association between prenatal phthalate exposure and body mass index (BMI) in CHAMACOS children, we used three advanced statistical methods: generalized additive models, growth mixture models, and functional principal component analysis with tree-based methods to identify patterns of childhood BMI development and allow for non-linear relationships with the environmental exposures. Our results highlight the heterogeneity in childhood BMI development patterns and suggest a sex-specific non-linear association between prenatal monoethyl phthalate urinary concentrations and BMI level in children, confirmed across a variety of statistical methods. There is also evidence to suggest positive associations between DEHP metabolites and BMI stabilization during puberty for girls., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Animal studies suggest that phthalates and bisphenol A (BPA), endocrine-disrupting chemicals found in many consumer products, may impact the timing of puberty., Objectives: We aimed to determine the association of prenatal exposure to high-molecular-weight phthalates and BPA with pubertal timing in boys and girls participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study., Methods: We quantified urinary concentrations of eight phthalate metabolites and BPA at two time points during pregnancy among participating mothers ([Formula: see text]) and conducted clinical Tanner staging of puberty on their children every 9 months between 9 and 13 y of age. We conducted accelerated failure time models and examined the role of child overweight/obese status in this association., Results: The sum of urinary metabolites of di(2-ethylhexyl) phthalate [Formula: see text], monobenzyl phthalate (MBzP), and BPA were associated with later onset of at least one of the three outcomes assessed in girls (thelarche, pubarche, or menarche) and with earlier onset of at least one of the two outcomes assessed in boys (gondarche and pubarche). We found that monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono(3-carboxypropyl) phthalate, and BPA were associated with later pubarche and menarche mostly among normal-weight girls but not overweight/obese girls. MBzP was associated with later thelarche in all girls, and [Formula: see text] was associated with later thelarche and menarche in all girls. BPA and all phthalate biomarkers were associated with earlier gonadarche and pubarche in all boys as well as in overweight/obese boys when stratified by weight. Among normal-weight boys, associations with BPA were also inverse, whereas associations with phthalate metabolites were close to the null or positive., Conclusions: Several high-molecular-weight phthalates and BPA were associated with later puberty in girls and earlier puberty in boys included in the CHAMACOS cohort study. Childhood overweight/obesity may modify these associations. https://doi.org/10.1289/EHP3424.

Objective: Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study, we assessed the association of in utero exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenylethylene (DDE) with child adiposity at age 12., Methods: We included 240 children with o,p'-DDT, p,p'-DDT, and p,p'-DDE concentrations measured in maternal serum collected during pregnancy (ng/g lipid) and complete 12-year follow-up data. Age- and sex-specific body mass index (BMI) z-scores were calculated from CDC growth charts. Children with BMI z-scores ≥ 85th percentile were classified as overweight or obese., Results: At 12 years, BMI z-score averaged 1.09 (±1.03) and 55.4% of children were overweight or obese. Prenatal DDT and DDE exposure was associated with several adiposity measures in boys but not girls. Among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased BMI z-score (o,p'-DDT, adj-β=0.37, 95% CI: 0.08, 0.65; p,p'-DDT, adj-β = 0.26, 95% CI: 0.03, 0.48; p,p'-DDE, adj-β = 0.31, 95% CI: 0.02, 0.59). Results for girls were nonsignificant. The difference by sex persisted after considering pubertal status., Conclusions: These results support the chemical obesogen hypothesis, that in utero exposure to DDT and DDE may increase risk of obesity in males later in life., (Copyright © 2017. Published by Elsevier Inc.)

Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine-disrupting chemicals (EDCs) in humans and animals. The purpose of this study is to examine the relationship of in utero and childhood exposure to these purported EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS, an ongoing birth cohort in California's Salinas Valley. We measured o,p'- and p,p'-DDT, p,p'-DDE, PBDEs and PCBs in serum collected from mothers during pregnancy or at delivery and from their sons at 9 years. We measured concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) from 234 of their sons at 12 years. In adjusted models, we found that a 10-fold increase in maternal prenatal serum concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0, 47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were associated with increases in boys' LH levels. A 10-fold increase in total prenatal ΣPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in FSH, primarily driven by non- dioxin-like congeners. Boys' hormone levels were only marginally associated with prenatal DDT or DDE in primary models, but when boys' Tanner stage at age 12 was added to models, prenatal maternal DDT levels were associated with decreases in LH (adjusted percent change per 10-fold increase=-18.5%, 95% CI: -29.8, -5.4) and T (percent change=-18.2%, 95% CI: -30.2, -4.2) and DDE with LH (percent change=-18.3%, 95% CI: -32.9, -0.6). Exposures measured in the children's serum at 9 years also showed associations between BDE-153 and ΣPCBs. However, there is evidence that these associations appear to be mediated by child BMI. This study suggests associations on male hormones of 12year old boys related to exposure to certain EDC exposure prenatally. The implications on future reproductive function in puberty and adulthood should be determined., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Polybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing., Methods: Study subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones., Results: Prenatal concentrations of all 4 congeners and ƩPBDEs were associated with later menarche in girls (RR earlier menarche =0.5, 95% confidence interval (CI): 0.3, 0.9 for ƩPBDEs) but earlier pubic hair development in boys (RR earlier pubarche =2.0, 95% CI: 1.3, 3.3 for ƩPBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche., Conclusions: We found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys., Competing Interests: The authors have no conflicts of interest., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Numerous cross-sectional studies of school-age children have observed that exposure to manganese (Mn) adversely affects neurodevelopment. However, few prospective studies have looked at the effects of both prenatal and postnatal Mn exposure on child neurodevelopment., Methods: We measured Mn levels in prenatal and early postnatal dentine of shed teeth and examined their association with behavior, cognition, memory, and motor functioning in 248 children aged 7, 9, and/or 10.5 years living near agricultural fields treated with Mn-containing fungicides in California. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects., Results: We observed that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely internalizing, externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years. In contrast, higher Mn levels in prenatal and postnatal dentine were associated with better memory abilities at ages 9 and 10.5, and better cognitive and motor outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn levels were also associated with poorer visuospatial memory outcomes at 9 years and worse cognitive scores at 7 and 10.5 years in children with higher prenatal lead levels (≥0.8 μg/dL). All these associations were linear and were consistent with findings from longitudinal analyses., Conclusions: We observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in school-age boys. Additional research is needed to understand the inconsistencies in the neurodevelopmental findings across studies and the degree to which differences may be associated with different Mn exposure pathways and biomarkers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Polybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems., Objective: In this study, we examined whether pre- and postnatal exposure to the components of pentaBDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California., Methods: We measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index (BMI) at age 7 years., Results: Maternal PBDE serum levels during pregnancy were associated with higher BMI z-scores in boys (BMI z-score βadjusted = 0.26; 95% CI: -0.19, 0.72) but lower scores in girls (BMI z-score βadjusted = -0.41; 95% CI: -0.87, -0.05) at 7 years of age (pinteraction = 0.04). In addition, child's serum BDE-153 concentration (log10), but not other pentaBDE congeners, demonstrated inverse associations with BMI at age 7 years (BMI z-score βadjusted = -1.15; 95% CI: -1.53, -0.77), but there was no interaction by sex., Conclusions: We estimated sex-specific associations with maternal PBDE levels during pregnancy and BMI at 7 years of age, finding positive associations in boys and negative associations in girls. Children's serum BDE-153 concentrations were inversely associated with BMI at 7 years with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.

In-utero exposure to endocrine-disrupting compounds, including dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE), has been hypothesized to increase the risk of obesity later in life. We examined the associations of maternal serum concentrations of DDT and DDE during pregnancy with body mass index, obesity, waist circumference, and percentage of body fat in 9-year-old children (n = 261) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort study in the Salinas Valley, California (2000-2010). We found associations between prenatal exposure to DDT and DDE and several measures of obesity at 9 years of age in boys but not in girls. For example, among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased odds of becoming overweight or obese (for o,p'-DDT, adjusted odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.0, 6.3; for p,p'-DDT, adjusted OR = 2.1, 95% CI: 1.0, 4.5; and for p,p'-DDE, adjusted OR = 1.97, 95% CI: 0.94, 4.13). The odds ratios for girls were nonsignificant. Results were similar for body mass index z score, waist circumference z score, and odds of increased waist circumference but were less consistent for percentage of body fat. The difference by sex persisted after considering pubertal status. These results provide support for the chemical obesogen hypothesis., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n = 358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P = 0.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children., Objectives: We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California., Methods: Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners' Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale., Results: Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2-1.2; ADHD: β = 1.3; 95% CI, 0.4-2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7-15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1-10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention., Conclusions: In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys.

Little information has been published about pesticide exposures experienced by pregnant women. We measured six dialkyl phosphate (DAP) urinary metabolites of organophosphate (OP) pesticides in 600 pregnant, low-income women living in the Salinas Valley, California, an agricultural area. A total of 28% were employed as farm fieldworkers during pregnancy, and 81% had at least one household member who worked in agriculture. Samples were collected twice during pregnancy (mean = 13 and 26 weeks' gestation, respectively) and just after delivery (mean = 9 days). As in other studies, dimethyldithiophosphate levels were higher than those of other urinary OP metabolites. Total DAP metabolite levels in samples collected after delivery were higher than in samples collected during pregnancy. Median metabolite levels at the first and second prenatal sampling points and at the postpartum collection were 102.8, 106.8, and 227.2 nmol/L, respectively. Both prenatal and postpartum metabolite levels were higher in these Salinas Valley women than in a sample of women of childbearing age in the general U.S. population (National Health and Nutrition Examination Survey), although the deviation from U.S. reference levels was most pronounced after delivery. Higher DAP metabolite levels in the immediate postpartum period may have implications for estimating dose during pregnancy and for exposure during lactation.