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Background: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied., Objective: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort., Methods: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑ 5 BDE: 28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log 10 -transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values., Results: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑ 5 BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑ 5 BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑ 5 BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑ 5 BDE)., Discussion: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph M Braun reports a relationship that included paid expert testimony related to PFAS-contaminated drinking water. All other authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Phthalates are a group of chemicals with ubiquitous exposure worldwide. Exposures to phthalates during pregnancy may play a role in autism spectrum disorder (ASD) etiology by disrupting hormone levels or directly impacting fetal neurodevelopment. However, there is little research quantifying the aggregate effect of phthalates on child ASD-related behaviors., Methods: We used data from two prospective pregnancy and birth cohorts-the Health Outcomes and Measures of the Environment (HOME) and the Early Autism Risk Longitudinal Investigation (EARLI). HOME is a general population cohort while participants in EARLI were at higher familial risk for ASD. Using quantile g-computation and linear regression models, we assessed the joint and individual associations of a mixture of six phthalate metabolites during pregnancy with child ASD-related traits measured by Social Responsiveness Scale (SRS) scores at ages 3-8 years., Results: Our analyses included 271 participants from HOME and 166 participants from EARLI. There were imprecise associations between the phthalate mixture and SRS total raw scores in HOME (difference in SRS scores per decile increase in every phthalate = 1.3; 95% confidence interval [CI] = -0.2, 2.8) and EARLI (difference in SRS scores per decile increase in every phthalate = -0.9; 95% CI = -3.5, 1.7)., Conclusions: The cohort-specific effect sizes of the pthalates-SRS associations were small and CIs were imprecise. These results suggest that if there are associations between phthalate metabolites during pregnancy and child SRS scores, they may differ across populations with different familial liabilities. Further studies with larger sample sizes are warranted., Competing Interests: J.B. was financially compensated for serving as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lead exposure is associated with behavioral problems in children, but the age(s) of greatest susceptibility to low-level lead exposure is unknown., Objective: We evaluated the association of repeated blood lead concentrations with parent-reported behaviors to identify periods of heightened susceptibility during infancy and childhood (HOME Study; Cincinnati, OH; 2003-2006; n = 244)., Methods: We quantified lead in whole blood samples (ages 1, 2, 3, 4, 5, and 8 years) and assessed behavior using the Behavioral Assessment System for Children-2 (BASC-2; ages 2, 3, 4, 5, and 8 years). We used multiple informant models and modified Poisson regression to estimate covariate-adjusted associations of ln-transformed blood lead concentrations with continuous BASC-2 T-scores and the relative risk of behavior scores classified as at-risk or clinically significant, respectively., Results: We observed trends indicating that higher blood lead concentrations at all ages were adversely associated with scores on behavioral scales. On the Externalizing Problems and Adaptive Skills scales, these associations were strongest for blood lead concentrations at age 8 years (β = 3.1-point; 95% CI = 0.7, 5.4 and β = -2.2-point; 95% CI = -4.9, 0.5, respectively) compared with other ages. Overall, higher blood lead concentrations were associated with elevated risk of behavior scores classified as at-risk or clinically significant on the Adaptive Skills, Behavioral Symptom Index, and Externalizing Problems scales., Significance: Contemporary levels of lead exposure during the first 8 years of life were associated with ADHD-related behaviors, specifically aggression, hyperactivity, and conduct problems., Impact Statement: Our results highlight the importance of primary lead prevention across childhood., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Many environmental chemicals are being identified as suspected neurotoxicants based on the findings of both experimental and epidemiological studies. Organophosphate esters (OPEs), which are among the chemicals that have replaced neurotoxic polybrominated diphenyl ethers (PBDEs) after 2004, have also become an important public health topic as evidence regarding their potential for early-life neurotoxicity is growing. In 233 mother child pairs from Cincinnati, OH, we measured concentrations of the OPE metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP) in the urine of pregnant women at 16 and 26 weeks gestation and at delivery. At age 8 years, we assessed children's cognition using the Wechsler Intelligence Scale for Children-IV. In models adjusted for maternal race, income, body mass index, and IQ, maternal urinary BCEP was associated with a modest increase in child full-scale IQ (ß: 0.81 per a ln-unit BCEP increase; 95 % CI: 0.00, 1.61) while other OPEs were not associated with changes in full-scale IQ or any IQ subscales. Maternal serum PBDE concentrations did not confound the relationships between urinary OPE metabolites and child IQ. Using Bayesian kernel machine regression, we did not find that concentrations of a mixture of OPE metabolites during gestation was associated with any child cognition measures. The results of this study are not consistent with other published work, and a larger sample size would be beneficial to explore potential associations more fully. Therefore, additional studies are necessary to continue studying prenatal OPE exposure and child neurodevelopment and behavior., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003-2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; ß = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes.

Objective: To investigate whether exposure to tobacco smoke during early brain development is linked with later problems in behavior and executive function., Study Design: We studied 239 children in a prospective birth cohort. We measured tobacco exposures by caregiver report and serum cotinine 3 times during pregnancy and 4 times during childhood. We used linear regression to examine the association between prenatal and childhood serum cotinine concentrations and behavior (the Behavior Assessment System for Children-2) and executive function (the Behavior Rating Inventory of Executive Function) at age 8 years while adjusting for important covariates., Results: Neither prenatal nor child serum cotinine were associated with behavior problems measured by the Behavior Assessment System for Children-2. On the Behavior Rating Inventory of Executive Function, prenatal and childhood exposure was associated with poorer task initiation scores (B = 0.44; 95% CI, 0.03-0.85 and B = 0.69, 95% CI, 0.06-1.32 respectively). Additionally, in a subset of 208 children with nonsmoking mothers, prenatal exposure was associated with task initiation scores (B = 1.17; 95% CI, 0.47-1.87) and additional components of the metacognition index (eg, working memory, B = 1.20; 95% CI, 0.34-2.06), but not components of the behavioral regulation index., Conclusions: Tobacco exposures during pregnancy (including low-level second-hand smoke) and childhood were associated with deficits in some domains of children's executive function, especially task initiation and metacognition. These results highlight that decreasing early exposure to tobacco smoke, even second-hand exposure, may support ideal brain functioning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Background: Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment., Objective: To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8years., Methods: We used data from 167 mother-child pairs recruited during pregnancy (2003-2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16±3weeks of gestation and childhood sera at ages 3 and 8years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5years and Wide Range Achievement Test-4 at age 8years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility., Results: Median serum PFASs concentrations were PFOS>PFOA>PFHxS>PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (β: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (β: 4.2, 95% CI: 0.5, 8.0) at age 8years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (β: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (β: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (β: 5.9, 95% CI: 1.5, 10.2) at age 5years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (β: 5.8, 95% CI: 0.8, 10.7) at age 8years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5years, but not at age 8years; 3-year PFOS and PFNA were positively associated with reading scores at age 5years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills., Conclusion: Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children's reading skills at ages 5 and 8years, but no association was found between serum PFHxS and reading skills., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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 socioeconomic 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., (© The Author 2016. 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.)

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.

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 (ΣDMP) 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., Citation: Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. 2016. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environ Health Perspect 124:822-830; http://dx.doi.org/10.1289/ehp.1409474.

Background: Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI)., Methods: We included 707 children from three prospective cohort studies enrolled in the US between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1 standard deviation increase in natural log phthalate metabolite concentrations and BMI z scores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child's sex, race/ethnicity, and cohort., Results: Mono-3-carboxypropyl phthalate concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z scores (β = -0.02 [-0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate and summed di-(2-ethylhexyl) phthalate metabolites (∑DEHP) concentrations were inversely associated with BMI z scores among girls (monoethyl phthalate beta = -0.14 [-0.28, 0.00]; ∑DEHP beta = -0.12 [-0.27, 0.02])., Conclusions: Maternal urinary mono-3-carboxypropyl phthalate, a nonspecific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not in boys, suggesting that prenatal exposures may have sexually dimorphic effects on physical development.

Background: Studies examining the effects of low-level gestational methylmercury exposure from fish consumption on infant neurobehavioral outcomes in the offspring are limited and inconclusive. Our objective was to examine the effects of low-level gestational exposure to methylmercury on neurobehavioral outcomes in early infancy., Methods: We assessed neurobehavior of 344 infants at 5-weeks using the NICU Network Neurobehavioral Scale (NNNS). Gestational mercury exposure was measured as whole blood total mercury (WBTHg) in maternal and cord blood. We collected fish consumption information and estimated polyunsaturated fatty acid (PUFA) intake. We examined the association between gestational mercury exposure and NNNS scales using regression, adjusting for covariates., Results: Geometric mean of maternal and cord WBTHg were 0.64 and 0.72 μg/L, respectively. Most mothers (84%) reported eating fish during pregnancy. Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls (p=0.04 for maternal WBTHg and p=0.03 for cord WBTHg), less need for special handling during the assessment (p=0.03 for cord WBTHg) and a trend of better attention (p=0.054 for both maternal WBTHg and cord WBTHg). Similarly, infants born to mothers with higher fish consumption or estimated PUFA intake also had increased asymmetric reflexes and less need for special handling. In models simultaneously adjusted for WBTHg and fish consumption (or PUFA intake), the previously observed WBTHg effects were attenuated; and higher fish consumption (or PUFA intake) was significantly associated with less need for special handling., Conclusions: In a cohort with low level mercury exposure and reporting low fish consumption, we found minimal evidence of mercury associated detrimental effects on neurobehavioral outcomes during early infancy. Higher prenatal mercury exposure was associated with more frequent asymmetric reflexes in girls. In contrast, infants with higher prenatal mercury exposure and those whose mothers consumed more fish had better attention and needed less special handling, which likely reflect the beneficial nutritional effects of fish consumption., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To assess the impact of prenatal exposure to polybrominated diphenyl ethers (PBDEs) and polyfluoroalkyl chemicals (PFCs) on early infant neurobehavior., Study Design: In a cohort of 349 mother/infant pairs, we measured maternal serum concentrations during pregnancy of PBDEs, including BDE-47 and other related congeners, as well as 2 common PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid. When the infants were 5 weeks of age, we measured their neurobehavior by using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)., Results: Neither PBDE nor PFC exposures during gestation were associated with the 11 individual NNNS outcomes included in our study; however, when we used latent profile analysis to categorize infants into neurobehavioral profiles based on performance on the NNNS (social/easygoing, high arousal/difficult, or hypotonic), a 10-fold increase in prenatal PFOA concentrations significantly increased the odds of being categorized as hypotonic compared with social/easygoing (aOR 3.79; 95% CI 1.1-12.8)., Conclusions: Infants of mothers with greater serum concentrations of PFOA during pregnancy were more likely to be categorized as hypotonic. No association between PBDE concentrations and hypotonia was found. Additional studies should further investigate possible associations of prenatal PFC exposure and muscle tone in infants and children., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Importance: Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, has been associated with wheezing in children, but few studies have examined its effect on lung function or wheeze in older children., Objectives: To test whether BPA exposure is associated with lung function, with wheeze, and with pattern of wheeze in children during their first 5 years., Design, Setting, and Participants: A birth cohort study, enrolled during early pregnancy in the greater Cincinnati, Ohio, area among 398 mother-infant dyads. We collected maternal urine samples during pregnancy (at 16 and 26 weeks) and child urine samples annually to assess gestational and child BPA exposure., Main Outcomes and Measures: We assessed parent-reported wheeze every 6 months for 5 years and measured child forced expiratory volume in the first second of expiration (FEV1) at age 4 and 5 years. We evaluated associations of BPA exposure with respiratory outcomes, including FEV1, child wheeze, and wheeze phenotype., Results: Urinary BPA concentrations and FEV1 data were available for 208 children and urinary BPA concentrations and parent-reported wheeze data were available for 360 children. The mean maternal urinary BPA concentration ranged from 0.53 to 293.55 µg/g of creatinine. In multivariable analysis, every 10-fold increase in the mean maternal urinary BPA concentration was associated with a 14.2% (95% CI, -24.5% to -3.9%) decrease in the percentage predicted FEV1 at 4 years, but no association was found at 5 years. In multivariable analysis, every 10-fold increase in the mean maternal urinary BPA concentration was marginally associated with a 54.8% increase in the odds of wheezing (adjusted odds ratio, 1.55; 95% CI, 0.91-2.63). While the mean maternal urinary BPA concentration was not associated with wheeze phenotype, a 10-fold increase in the 16-week maternal urinary BPA concentration was associated with a 4.27-fold increase in the odds of persistent wheeze (adjusted odds ratio, 4.27; 95% CI, 1.37-13.30). Child urinary BPA concentrations were not associated with FEV1 or wheeze., Conclusions and Relevance: These results provide evidence suggesting that prenatal but not postnatal exposure to BPA is associated with diminished lung function and the development of persistent wheeze in children.

Background: National data suggest widespread gestational exposure to organophosphate pesticides (OPs) based on the detection of OP metabolites in the urine of pregnant women. Associations with early infant neurobehavior are largely understudied, with only two studies reporting abnormal reflexes in newborns in association with gestational exposure to OPs. Our objective was to utilize biological markers of OP metabolites in pregnant women and a comprehensive assessment of infant neurobehavior to determine the association of gestational exposure to OPs with neurobehavioral outcomes during early infancy., Methods: Among a cohort of 350 mother/infant pairs, we measured six common dialkylphosphate metabolites of OP pesticides in maternal urine, at two times during pregnancy (16 w & 26 w gestation), then calculated aggregate concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate metabolites. We measured infant neurobehavior at about five weeks of age using the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of neurobehavior in young infants. Analyses of associations between gestational exposure to OPs and neurobehavior at five weeks included multiple linear and logistic regression., Results: After adjustment for covariates, higher creatinine-corrected urinary concentrations of diethylphosphate metabolites were associated with improved attention and reduced lethargy and hypotonia in young infants. Higher creatinine-corrected urinary concentrations of total dialkylphosphate metabolites were associated with fewer signs of autonomic stress. Women who were white, married, had advanced education, and reported more frequent consumption of fresh fruits and vegetables had higher concentrations of OP metabolites during pregnancy., Conclusions: In this sample of pregnant women whose urinary concentrations of dialkylphosphate metabolites are representative of national exposure levels, we found no detrimental effects of gestational exposure to OPs on neurobehavioral outcomes among young infants. These results are important as they suggest there may be minimal to no detectable adverse impact of low level prenatal OP exposure on the neurobehavior of young infants.

Background: Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants., Methods: NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined., Results: Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles., Conclusions: Three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations., (© 2012 Blackwell Publishing Ltd.)

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.

Objective: To examine the association of prenatal exposure to bisphenol A and select common phthalates with infant neurobehavior measured at 5 weeks., Methods: We compared the concentration of maternal urinary metabolites of bisphenol A and phthalates at two distinct time points in pregnancy (16w, 26w) with scores on the NICU Network Neurobehavioral Scale (NNNS) at 5 weeks of age in a cohort of 350 mother/infant pairs., Results: Prenatal exposure to BPA was not significantly associated with neurobehavioral outcomes at 5 weeks. Significant associations between prenatal exposure to measured phthalates and infant neurobehavioral outcomes differed by type of phthalate and were only seen with exposure measured at 26 weeks. Higher total di-butyl phthalate (DBP) metabolites at 26w were associated with improved behavioral organization evidenced by decreased arousal (p=.04), increased self-regulation (p=.052), and decreased handling (p=.02). In males, higher total di-2-ethylhexyl phthalate (DEHP) metabolites at 26w were associated with more nonoptimal reflexes (p=.02)., Conclusion: The association between prenatal phthalate exposure and infant neurobehavior differed by type of phthalate and was evident only with exposure measured at 26w. Prenatal exposure to DBP was associated with improved behavioral organization in 5-week-old infants. Prenatal exposure to DEHP was associated with nonoptimal reflexes in male infants. There was no evidence of an association between prenatal BPA exposure and infant neurobehavior., (Copyright © 2011 Elsevier Inc. All rights reserved.)