Dataset Information

Prenatal organophosphate ester exposure and executive function in Norwegian preschoolers.

ABSTRACT: Organophosphate esters (OPEs) are ubiquitous chemicals, used as flame retardants and plasticizers. OPE usage has increased over time as a substitute for other controlled compounds. This study investigates the impact of prenatal OPE exposure on executive function (EF) in preschoolers.

Methods

We selected 340 preschoolers from the Norwegian Mother, Father, and Child Cohort Study. Diphenyl-phosphate (DPhP), di-n-butyl-phosphate (DnBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were measured in maternal urine. EF was measured using the Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P) and the Stanford-Binet fifth edition (SB-5). EF scores were scaled so a higher score indicated worse performance. We estimated exposure-outcome associations and evaluated modification by child sex using linear regression.

Results

Higher DnBP was associated with lower EF scores across multiple rater-based domains. Higher DPhP and BDCIPP were associated with lower SB-5 verbal working memory (β = 0.49, 95% CI = 0.12, 0.87; β = 0.53, 95% CI = 0.08, 1.02), and higher BBOEP was associated with lower teacher-rated inhibition (β = 0.34, 95% CI = 0.01, 0.63). DPhP was associated with lower parent-reported BRIEF-P measures in boys but not girls [inhibition: boys: 0.37 (95% CI = 0.03, 0.93); girls: -0.48 (95% CI = -1.27, 0.19); emotional control: boys: 0.44 (95% CI = -0.13, 1.26); girls: -0.83 (95% CI = -1.73, -0.00); working memory: boys: 0.49 (95% CI = 0.03, 1.08); girls: -0.40 (95% CI = -1.11, 0.36)]. Fewer sex interactions were observed for DnBP, BBOEP, and BDCIPP, with irregular patterns observed across EF domains.

Conclusions

We found some evidence prenatal OPE exposure may impact EF in preschoolers and variation in associations by sex.

SUBMITTER: Hall AM

PROVIDER: S-EPMC10256412 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prenatal organophosphate ester exposure and executive function in Norwegian preschoolers.

Hall Amber M AM Keil Alexander P AP Choi Giehae G Ramos Amanda M AM Richardson David B DB Olshan Andrew F AF Martin Chantel L CL Villanger Gro D GD Reichborn-Kjennerud Ted T Zeiner Pål P Øvergaard Kristin R KR Sakhi Amrit K AK Thomsen Cathrine C Aase Heidi H Engel Stephanie M SM

Environmental epidemiology (Philadelphia, Pa.) 20230605 3

Organophosphate esters (OPEs) are ubiquitous chemicals, used as flame retardants and plasticizers. OPE usage has increased over time as a substitute for other controlled compounds. This study investigates the impact of prenatal OPE exposure on executive function (EF) in preschoolers.<h4>Methods</h4>We selected 340 preschoolers from the Norwegian Mother, Father, and Child Cohort Study. Diphenyl-phosphate (DPhP), di-n-butyl-phosphate (DnBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(1,3-dichlo ...[more]

PMID: 37304339

Similar Datasets

Project description:IntroductionPrenatal exposure to organophosphorus pesticides (OPPs) has been associated with neurodevelopmental deficits in children, however evidence linking OPPs with specific cognitive mechanisms, such as executive function (EF), is limited.ObjectiveThis study aims to evaluate the association between prenatal exposure to OPPs with multiple measures of EF in preschool-aged children, while considering the role of variant alleles in OPP metabolism genes.MethodsWe included 262 children with preschool attention-deficit/hyperactivity disorder (ADHD), and 78 typically developing children, from the Preschool ADHD substudy of the Norwegian, Mother, Father, and Child Cohort Study. Participants who gave birth between 2004 and 2008 were invited to participate in an on-site clinical assessment when the child was approximately 3.5 years; measurements of EF included parent and teacher rating on Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), and three performance-based assessments. We measured OPP metabolites in maternal urines collected at ∼17 weeks' gestation to calculate total dimethyl- (ΣDMP) and diethyl phosphate (ΣDEP) metabolite concentrations. We estimated multivariable adjusted β's and 95% confidence intervals (CIs) corresponding to a change in z-score per unit increase in log-ΣDMP/DEP. We further characterized gene-OPP interactions for maternal variants in PON1 (Q192R, M55L), CYP1A2 (1548T > C), CYP1A1 (IntG > A) and CYP2A6 (-47A > C).ResultsPrenatal OPP metabolite concentrations were associated with worse parent and teacher ratings of emotional control, inhibition, and working memory. A one log-∑DMP increase was associated with poorer teacher ratings of EF on the BRIEF-P (e.g. emotional control domain: β = 0.55, 95% CI: 0.35, 0.74), when weighted to account for sampling procedures. We found less consistent associations with performance-based EF assessments. We found some evidence of modification for PON1 Q192R and CYP2A6 -47A > C. Association with other variants were inconsistent.ConclusionsBiomarkers of prenatal OPP exposure were associated with more adverse teacher and parent ratings of EF in preschool-aged children.

Project description:BackgroundAttention-deficit/hyperactivity-disorder (ADHD) is a leading neurodevelopmental disorder in children worldwide; however, few modifiable risk factors have been identified. Organophosphate esters (OPEs) are ubiquitous chemical compounds that are increasingly prevalent as a replacement for other regulated chemicals. Current research has linked OPEs to neurodevelopmental deficits. The purpose of this study was to assess gestational OPE exposure on clinically-assessed ADHD in children at age 3 years.MethodsIn this nested case-control study within the Norwegian Mother, Father, and Child Cohort study, we evaluated the impact of OPE exposure at 17 weeks' gestation on preschool-age ADHD. Between 2007 and 2011, 260 ADHD cases were identified using the Preschool Age Psychiatric Assessment and compared to a birth-year-stratified control group of 549 children. We categorized bis(2-butoxyethyl) phosphate (BBOEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) as values < limit of detection (LOD) (BBOEP N = 386, BDCIPP N = 632), ≥LOD but < limit of quantification (LOQ) (BBOEP N = 413; BDCIPP N = 75), or above LOQ (BBOEP N = 70; BDCIPP N = 102). Diphenyl phosphate (DPhP) and di-n-butyl phosphate (DnBP) were categorized as quartiles and also modeled with a log10 linear term. We estimated multivariable adjusted odds ratios (ORs) using logistic regression and examined modification by sex using an augmented product term approach.ResultsMothers in the 3rd DnBP quartile had 1.71 times the odds of having a child with ADHD compared to the 1st quartile (95%CI: 1.13, 2.58); a similar trend was observed for log10 DnBP and ADHD. Mothers with BDCIPP ≥ LOD but < LOQ had 1.39 times the odds of having a child with ADHD compared to those with BDCIPP < LOD (95%CI: 0.83, 2.31). Girls had lower odds of ADHD with increasing BBOEP exposure (log10 OR: 0.55 (95%CI: 0.37, 0.93), however boys had a weakly increased odds (log10 OR: 1.25 (95%CI: 0.74, 2.11) p-interaction = 0.01].ConclusionsWe found modest increased odds of preschool ADHD with higher DnBP and BDCIPP exposure.

Project description:BackgroundLead is an established neurotoxicant and early life exposure to lead is associated with detrimental impacts on IQ and several neurobehavioral domains. Less is known, however, about effects of prenatal lead exposure below 5 μg/dL on executive function and on social, emotional and self-regulatory behaviors in childhood.ObjectivesTo examine the association between prenatal lead exposure and childhood executive function and social, emotional and self-regulatory behaviors.MethodsWe included 1006 mother-child pairs from the Project Viva prospective pre-birth cohort. We measured prenatal maternal lead in second-trimester erythrocytes. In mid-childhood (median 7.7 years), parents and teachers rated executive function related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ). We used multivariable linear regression models adjusted for maternal, paternal, and child characteristics and metal co-exposures.ResultsMean maternal erythrocyte lead concentration was 1.2 μg/dL (interquartile range [IQR] 0.8-1.5 μg /dL), equivalent to approximately 0.4 μg/dL in whole blood. In adjusted models, associations with parent and teacher-rated scales were largely null, although effect estimates were consistently positive, suggesting worse scores with increasing lead levels. For an IQR increase in lead, BRIEF Global Executive Composite (GEC) was 0.73 (95% CI: -0.06, 1.52) points higher for parent-rated scores and 0.42 (95% CI: -0.39, 1.23) points higher for teacher-rated scores. Associations were strongest for parent-rated BRIEF plan/organize (β = 0.85; 95% CI: 0.12, 1.59) and shift (β = 0.88; 95% CI: 0.01, 1.75) subscales, as well as the SDQ emotional problems subscale (β = 0.18; 95% CI: 0.03, 0.33).DiscussionIn this cohort with lead levels commonly experienced by U.S. women, there were few statistically significant associations with childhood executive function and behavior. However, there was a trend of worse neurobehavioral scores with increasing prenatal lead concentrations, in particular for childhood emotional problems and capacity to plan/organize and shift. Our results highlight the importance of continuing efforts to eliminate lead exposure in the general population.

Project description:Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (ORfine = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (pinteraction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (pinteraction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males ORgross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males ORfine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.

Project description:BackgroundTraffic-related air pollution exposure may influence brain development and function and thus be related to neurobehavioral problems in children, but little is known about windows of susceptibility.AimsExamine associations of gestational and childhood exposure to traffic-related pollution with executive function and behavior problems in children.MethodsWe studied associations of pre- and postnatal pollution exposures with neurobehavioral outcomes in 1212 children in the Project Viva pre-birth cohort followed to mid-childhood (median age 7.7years). Parents and classroom teachers completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ). Using validated spatiotemporal models, we estimated exposure to black carbon (BC) and fine particulate matter (PM2.5) in the third trimester of pregnancy, from birth to 3years, from birth to 6years, and in the year before behavioral ratings. We also measured residential distance to major roadways and near-residence traffic density at birth and in mid-childhood. We estimated associations of BC, PM2.5, and other traffic exposure measures with BRIEF and SDQ scores, adjusted for potential confounders.ResultsHigher childhood BC exposure was associated with higher teacher-rated BRIEF Behavioral Regulation Index (BRI) scores, indicating greater problems: 1.0 points (95% confidence interval (CI): 0.0, 2.1) per interquartile range (IQR) increase in birth-age 6BC, and 1.7 points (95% CI: 0.6, 2.8) for BC in the year prior to behavioral ratings. Mid-childhood residential traffic density was also associated with BRI score (0.6, 95% CI: 0.1, 1.1). Birth-age 3BC was not associated with BRIEF or SDQ scores. Third trimester BC exposure was not associated with teacher-rated BRI scores (-0.2, 95% CI: -1.1, 0.8), and predicted lower scores (fewer problems) on the BRIEF Metacognition Index (-1.2, 95% CI: -2.2, -0.2) and SDQ total difficulties (-0.9, 95% CI: -1.4, -0.4). PM2.5 exposure was associated with teacher-rated BRIEF and SDQ scores in minimally adjusted models but associations attenuated with covariate adjustment. None of the parent-rated outcomes suggested adverse effects of greater pollution exposure at any time point.ConclusionsChildren with higher mid-childhood exposure to BC and greater near-residence traffic density in mid-childhood had greater problems with behavioral regulation as assessed by classroom teachers, but not as assessed by parents. Prenatal and early childhood exposure to traffic-related pollution did not predict greater executive function or behavior problems; third trimester BC was associated with lower scores (representing fewer problems) on measures of metacognition and behavioral problems.

Project description:BackgroundEvidence suggests organophosphate esters (OPEs) are neurotoxic; however, the epidemiological literature remains scarce. We investigated whether prenatal exposures to OPEs were associated with child neurobehavior in the MADRES cohort.MethodsWe measured nine OPE metabolites in 204 maternal urine samples (gestational age at collection: 31.4 ± 1.8 weeks). Neurobehavior problems were assessed among 36-month-old children using the Child Behavior Checklist's (CBCL) three composite scales [internalizing, externalizing, and total problems]. We examined associations between tertiles of prenatal OPE metabolites (> 50% detection) and detect/non-detect categories (< 50% detection) and CBCL composite scales using linear regression and generalized additive models. We also examined mixtures for widely detected OPEs (n = 5) using Bayesian kernel machine regression.ResultsMaternal participants with detectable versus non-detectable levels of bis(2-methylphenyl) phosphate (BMPP) had children with 42% (95% CI: 4%, 96%) higher externalizing, 45% (-2%, 114%) higher internalizing, and 35% (3%, 78%) higher total problems. Participants in the second versus first tertile of bis(butoxethyl) phosphate (BBOEP) had children with 43% (-1%, 109%) higher externalizing scores. Bis(1-chloro-2-propyl) phosphate (BCIPP) and child sex had a statistically significant interaction in internalizing (p = 0.02) and total problems (p = 0.03) models, with 120% (23%, 295%) and 57% (6%, 134%) higher scores in the third versus first BCIPP tertile among males. Among females, detectable vs non-detectable levels of prenatal BMPP were associated with 69% higher externalizing scores (5%, 170%) while the third versus first tertile of prenatal BBOEP was associated with 45% lower total problems (-68%, -6%). Although the metabolite mixture and each CBCL outcome had null associations, we observed marginal associations between di-n-butyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and higher internalizing scores (0.15; 95% CrI: -0.02, 0.32), holding other metabolites at their median.ConclusionsOur results generally suggest adverse and sex-specific effects of prenatal exposure to previously understudied OPEs on neurobehavioral outcomes in 36-month children, providing evidence of potential OPE neurotoxicity.

Dataset Information

Prenatal organophosphate ester exposure and executive function in Norwegian preschoolers.

Methods

Results

Conclusions

Publications

Prenatal organophosphate ester exposure and executive function in Norwegian preschoolers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets