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Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study.

ABSTRACT: Prenatal exposure to organophosphate insecticides may be associated with autism spectrum disorders and related behaviors. This association may be modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme.We examined the relationship of prenatal organophosphate insecticide biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8-year old children, and modification of this relationship by child PON1 polymorphisms.Among 224 pregnant women, we quantified concentrations of six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When children were eight years old, we administered the Social Responsiveness Scale (SRS), a continuous measure of various dimensions of interpersonal behavior, communication, and repetitive/stereotypic behaviors. We estimated the association between a 10-fold increase in the sum of six DAP concentrations (?DAP) and SRS scores. We examined whether child PON1192 and PON1-108 genotypes modified this association.After covariate adjustment, ?DAP concentrations were not associated with SRS scores [?=-1.2; 95% confidence interval (CI): -4.0, 1.6]. Among children with the PON1-108TT genotype, ?DAP concentrations were associated with 2.5-point higher (95% CI: -4.9, 9.8) SRS scores; however, the association was not different from the 1.8-point decrease (95% CI: -5.8, 2.2) among children with PON1-108CT/CC genotypes (?DAP × PON1-108 p-value =0.54). The association between ?DAP concentrations and SRS scores was not modified by PON1192 (?DAP × PON1192 p-value =0.89).In this cohort, prenatal urinary DAP concentrations were not associated with children's social behaviors; these associations were not modified by child PON1 genotype.

SUBMITTER: Millenson ME

PROVIDER: S-EPMC5506847 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study.

Millenson Marisa E ME Braun Joseph M JM Calafat Antonia M AM Barr Dana Boyd DB Huang Yen-Tsung YT Chen Aimin A Lanphear Bruce P BP Yolton Kimberly K

Environmental research 20170511

<h4>Background</h4>Prenatal exposure to organophosphate insecticides may be associated with autism spectrum disorders and related behaviors. This association may be modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme.<h4>Objective</h4>We examined the relationship of prenatal organophosphate insecticide biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8-year old children, and modification of this relationship by child PON1 polymorphisms.<h4>Meth ...[more]

PMID: 28501654

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Project description:OBJECTIVE:To evaluate whether urinary concentrations of organophosphate flame retardant (PFR) metabolites are associated with pregnancy loss among women conceiving with assisted reproductive technology (ART). DESIGN:Prospective preconception cohort of subfertile women. SETTING:Academic hospital fertility center in Boston, Massachusetts. PATIENT(S):A total of 155 women conceiving 179 pregnancies with ART. INTERVENTION(S):None. Mean exposure to each of five PFR metabolites was estimated by averaging the specific-gravity adjusted natural log concentrations from two urine samples collected during the ART cycle of conception. MAIN OUTCOME MEASURE(S):Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for biochemical and total pregnancy loss (all losses <20 weeks' gestation) by quartiles of PFR metabolite concentrations were estimated using a repeated measures log-binomial model, accounting for multiple pregnancies per woman. RESULT(S):Of the 179 pregnancies, 31% ended in pregnancy loss (12% in biochemical loss). Among the three metabolites with high detection frequency [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), and isopropylphenyl phenyl phosphate (ip-PPP)], an increased risk of biochemical loss was observed for women with DPHP concentrations in the fourth vs. first quartile (RR 1.64; 95% CI 0.61-4.39). Also found was an elevated risk of biochemical pregnancy loss among women in the highest quartile of the molar sum of urinary PFR metabolites compared with the lowest (RR 1.89; 95% CI 0.64-5.58). Urinary concentrations of ip-PPP and BDCIPP were not associated with either outcome. CONCLUSION(S):Among subfertile women, urinary DPHP metabolite concentrations measured during the ART cycle of conception may be associated with early pregnancy loss. Although this study is uniquely designed to investigate early markers of pregnancy success and maintenance, the small sample size likely contributed to imprecision. Given their increasing use as replacement chemicals for traditional flame retardants, exposure to PFRs may increase, and more studies will be needed to investigate their potential to impact pregnancy and reproduction.

Project description:BackgroundPrenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings.ObjectiveThe objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands.MethodMaternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18 weeks, 18-25 weeks, and > 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders.ResultsMedian DAP metabolite concentration was 309 nmol/g creatinine at <18 weeks, 316 nmol/g creatinine at 18-25 weeks, and 308 nmol/g creatinine at >25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: -0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected.ConclusionsIn this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.

Project description:BackgroundEndocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult.ObjectiveOur goal was to identify gestational EDC exposures associated with autistic behaviors.MethodsWe measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a two-stage hierarchical analysis to account for repeated measures and confounding by correlated EDCs.ResultsMost of the EDCs were associated with negligible absolute differences in SRS scores (? 1.5). Each 2-SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE-28) (? = 2.5; 95% CI: -0.6, 5.6) or trans-nonachlor (? = 4.1; 95% CI: 0.8-7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB-178 (? = -3.0; 95% CI: -6.3, 0.2), ?-hexachlorocyclohexane (? = -3.3; 95% CI: -6.1, -0.5), or PBDE-85 (? = -3.2; 95% CI: -5.9, -0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (? = -2.0; 95% CI: -4.4, 0.4).ConclusionsSome EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, ?-hexachlorocyclohexane, PCB-178, PBDE-28, PBDE-85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors.

Project description:BACKGROUND:Organophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exposures with birth outcomes and cord blood adipokine and insulin concentrations. METHODS:We analyzed five OPE metabolites in urine samples collected at up to three visits during pregnancy from 90 women enrolled in the ORigins of Child Health And Resilience in Development (ORCHARD) pregnancy cohort in Baltimore, MD from 2017 to 2019. To quantify the variability of metabolite concentrations during pregnancy, we calculated intraclass correlation coefficients (ICCs) for each metabolite using mixed effects regression models. Using self-reported questionnaire data collected during gestation, we assessed possible sociodemographic and environmental/behavioral predictors of each OPE metabolite using generalized estimating equations to account for repeated exposure measures. We ascertained birth outcomes of 76 offspring from medical records, including weight-for-gestational age, length, ponderal index, and gestational age. In a subset of 37 infants, we measured cord blood concentrations of leptin, adiponectin, and insulin. To account for repeated exposure measures, we used linear structural equation models to assess the relations of standard deviation (SD) increases in prenatal OPE metabolite factor scores with continuous birth outcomes and cord blood biomarker concentrations. RESULTS:ICCs ranged from 0.09 for isopropylphenyl-phenyl phosphate (ip-PPP) to 0.59 for bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We observed little consistency in environmental or behavioral predictors of OPE exposures, although concentrations were generally lower for samples collected in the afternoon compared to morning and winter compared to other seasons. In adjusted analyses, a SD increase in BDCIPP concentration was associated with a 0.06?g/cm3 (95% CI: 0.00, 0.12) greater ponderal index. A SD increase in BDCIPP was associated with a 0.37 (95% CI: -?0.62, -?0.13) SD lower insulin concentration and 0.24 (95% CI: -?0.39, -?0.08) SD lower leptin concentration. Other OPEs were not associated with infant outcomes. CONCLUSIONS:These findings suggest some OPEs may be metabolic disruptors warranting investigation in larger studies.

Dataset Information

Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study.

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Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study.

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