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Organophosphate Pesticide Metabolite Concentrations in Urine during Pregnancy and Offspring Nonverbal IQ at Age 6 Years.

ABSTRACT: BACKGROUND:Susceptibility to organophosphate (OP) pesticide neurotoxicity may be greatest during the prenatal period; however, previous studies have produced mixed findings concerning in utero OP pesticide exposure and child cognition. OBJECTIVES:Our objective was to determine whether maternal urinary concentrations of OP pesticide metabolites are inversely associated with child nonverbal IQ at 6 y of age and to examine potential effect measure modification by the PON1 gene. METHODS:Data came from 708 mother–child pairs participating in the Generation R Study. Maternal urine concentrations of six dialkylphosphates (DAPs), collected at [Formula: see text], 18–25, and [Formula: see text] of gestation, were determined. Child nonverbal IQ was measured at 6 y of age using the Mosaics and Categories subtests from the Snijders-Oomen Nonverbal Intelligence Test-Revised. PON1 was determined in cord blood for 474 infants. Multiple linear regression models were fit to estimate the DAP-IQ associations and PON1 interactions. RESULTS:Overall, associations between child nonverbal IQ and maternal DAP concentrations were small and imprecise, and these associations were inconsistent across urine sampling periods. Howover, for a 10-fold difference in total DAP concentration for the [Formula: see text] of gestation samples, adjusted child nonverbal IQ was 3.9 points lower (95% CI: [Formula: see text], [Formula: see text]). Heterogeneity in the DAP–IQ association by PON1 gene allele status was not observed ([Formula: see text]). CONCLUSIONS:Consistent evidence of an association between higher maternal urinary DAP concentrations and lower child IQ scores at 6 y of age was not observed. There was some evidence for an inverse relation of child nonverbal IQ and late pregnancy urinary DAPs, but the estimated association was imprecise. https://doi.org/10.1289/EHP3024.

SUBMITTER: Jusko TA

PROVIDER: S-EPMC6381821 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Organophosphate Pesticide Metabolite Concentrations in Urine during Pregnancy and Offspring Nonverbal IQ at Age 6 Years.

Jusko Todd A TA van den Dries Michiel A MA Pronk Anjoeka A Shaw Pamela A PA Guxens Mònica M Spaan Suzanne S Jaddoe Vincent W VW Tiemeier Henning H Longnecker Matthew P MP

Environmental health perspectives 20190101 1

<h4>Background</h4>Susceptibility to organophosphate (OP) pesticide neurotoxicity may be greatest during the prenatal period; however, previous studies have produced mixed findings concerning <i>in utero</i> OP pesticide exposure and child cognition.<h4>Objectives</h4>Our objective was to determine whether maternal urinary concentrations of OP pesticide metabolites are inversely associated with child nonverbal IQ at 6 y of age and to examine potential effect measure modification by the <i>PON1</ ...[more]

PMID: 30688513

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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:BackgroundPrenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester.ObjectiveWe examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age.MethodThe study sample consisted of 1,282 mother-child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002-2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at <18, 18-25, and >25 wks of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test-Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy.ResultsHigher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular weight phthalates=-1.7 (95% CI: -3.1, -0.3)]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di-n-octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex.ConclusionsWe did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.

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:BackgroundThough prenatal organophosphate pesticide (OP) exposure has been associated with lower intellectual quotient and behavioral disorders in childhood, factors related to later delinquency, no research has directly evaluated the impact of OPs on delinquency.ObjectiveTo evaluate the association between prenatal and childhood OP exposure and juvenile delinquency in Mexican-American youth in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS).MethodsWe measured dialkyl phosphate (DAPs) urinary metabolites of OPs in two prenatal maternal samples and in five child samples collected between six months and five years of age. Youth completed delinquency questionnaires at 16 years. We examined associations of prenatal and childhood DAPs with several delinquency outcomes (n = 313) using survival and generalized linear models.ResultsAlmost 60% of youth reported delinquent acts (mostly minor), and 8% reported a police arrest. We observed largely null results of prenatal or childhood DAP concentrations and delinquency outcomes, with some isolated associations. A ten-fold increase in maternal dimethylphosphate (DM) concentrations measured after 20 weeks gestation was associated with an earlier age of first delinquent act (Hazard Ratio = 1.38, 95% CI: 1.01, 1.88) and an increased Odds Ratio (OR) of having committed 1-3 or ≥4 delinquent acts, compared to the no delinquency reference group (OR = 1.77, 95% CI: 1.01-3.08 and 2.17, 95% CI: 1.13-4.17, respectively). Higher childhood diethylphosphate (DE) concentrations were associated with a later age of first delinquent act (HR: 0.67; 95% CI: 0.46-0.97).DiscussionWe did not find strong evidence of association between prenatal or childhood OP exposure and juvenile delinquency in the present cohort. There is an increasing literature that relates OP exposure to neurobehavioral impairments in childhood, and there is a need to understand long-term potential neurodevelopmental effects of early-life OP exposure.

Dataset Information

Organophosphate Pesticide Metabolite Concentrations in Urine during Pregnancy and Offspring Nonverbal IQ at Age 6 Years.

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Organophosphate Pesticide Metabolite Concentrations in Urine during Pregnancy and Offspring Nonverbal IQ at Age 6 Years.

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