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Prenatal lead exposure and childhood executive function and behavioral difficulties in project viva.

ABSTRACT: BACKGROUND:Lead 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??g/dL on executive function and on social, emotional and self-regulatory behaviors in childhood. OBJECTIVES:To examine the association between prenatal lead exposure and childhood executive function and social, emotional and self-regulatory behaviors. METHODS:We 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. RESULTS:Mean maternal erythrocyte lead concentration was 1.2??g/dL (interquartile range [IQR] 0.8-1.5??g /dL), equivalent to approximately 0.4??g/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 (??=?0.85; 95% CI: 0.12, 1.59) and shift (??=?0.88; 95% CI: 0.01, 1.75) subscales, as well as the SDQ emotional problems subscale (??=?0.18; 95% CI: 0.03, 0.33). DISCUSSION:In 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.

SUBMITTER: Fruh V

PROVIDER: S-EPMC6842061 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Prenatal lead exposure and childhood executive function and behavioral difficulties in project viva.

Fruh Victoria V Rifas-Shiman Sheryl L SL Amarasiriwardena Chitra C Cardenas Andres A Bellinger David C DC Wise Lauren A LA White Roberta F RF Wright Robert O RO Oken Emily E Claus Henn Birgit B

Neurotoxicology 20190909

<h4>Background</h4>Lead 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.<h4>Objectives</h4>To examine the association between prenatal lead exposure and childhood executive function and social, emotional and self-regulatory behaviors. ...[more]

PMID: 31513824

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Project description:Early life exposure to per- and polyfluoroalkyl substances (PFAS) may adversely impact neurodevelopment, but epidemiological findings are inconsistent. In the Project Viva pre-birth cohort, we examined associations of prenatal and childhood PFAS plasma concentrations with parent and teacher assessments of children's behavior problems [Strengths and Difficulties Questionnaire (SDQ)] and executive function abilities [Behavior Rating Inventory of Executive Function (BRIEF)] at age 6-10 years (sample sizes 485-933). PFAS concentrations in pregnant Project Viva mothers (in 1999-2002) and children at ages 6-10 (in 2007-10) were similar to concentrations at similar time points in women and children in the nationally representative U.S. National Health and Nutrition Examination Survey. We observed no consistent associations of prenatal PFAS concentrations with behavior or executive function. Childhood concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) were associated with higher parent-rated SDQ Total Difficulties scores (mean = 6.7, standard deviation (SD) = 4.9), suggesting greater behavioral problems (top (Q4) versus bottom (Q1) quartile PFOA: 1.5, 95% confidence interval (CI): 0.3, 2.7; PFOS: 1.4, 95% CI: 0.3, 2.5; PFHxS: 1.2, 95% CI: 0.1, 2.3; PFNA: 1.2, 95% CI: 0.1, 2.2; PFDA: 1.1, 95% CI: 0.0, 1.1); teacher-rated SDQ scores did not show associations. Higher childhood PFOS was associated with higher (indicating more problems) parent-rated BRIEF General Executive Composite (GEC) scores (standardized to mean = 50, SD = 10) (Q4 vs. Q1: 2.4, 95% CI: 0.2, 4.6), while teacher BRIEF GEC scores indicated more problems among children with higher PFHxS (Q4 vs. Q1: 3.5, 95% CI: -0.8, 6.3). There were no consistent patterns of sexual dimorphism in associations. In a cohort of U.S. children, we observed cross-sectional associations of childhood PFAS concentrations with greater behavioral and executive function problems, but no consistent associations with prenatal PFAS.

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:BackgroundPerfluoroalkyl substances (PFAS) are suggested to interfere with thyroid hormone during pregnancy and influence fetal neurodevelopment. Epidemiological evidence regarding behavioral difficulties in childhood associated with prenatal PFAS exposure has been inconclusive.ObjectiveWe evaluated the association between prenatal PFAS exposure and behavioral difficulties at 7 and 11 years, and investigated the potential mediating role of maternal thyroid hormones.MethodsUsing pooled samples in the Danish National Birth Cohort established between 1996 and 2002, we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child behavioral assessments from the Strength and Difficulties Questionnaire (SDQ), reported by parents at 7 years (n = 2421), and by parents (n = 2070) and children at 11 years (n = 2071). Behavioral difficulties were defined as having a composite SDQ score above the 90th percentile for total difficulties and externalizing or internalizing behaviors. We used logistic regression to estimate the adjusted Odds Ratio (OR) by doubling increase of prenatal PFAS (ng/ml). The possible mediating effect of maternal thyroid function classified based on thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were evaluated.ResultsPrenatal perfluorononanoic acid (PFNA) was consistently associated with total and externalizing behavioral difficulties in all three SDQ measures reported by parents (OR = 1.40, 95% CI: 1.14-1.73 for age 7; OR = 1.27, 95% CI: 1.05-1.53 for age 11) or children (OR = 1.32, 95% CI: 1.11-1.58) while no consistent associations were observed for other types of PFAS. A small magnitude of natural indirect effects via maternal thyroid dysfunction (ORs ranged from 1.01 to 1.03) of several PFAS were observed for parent-reported total and externalizing behaviors at 7 years only.DiscussionPrenatal PFNA exposure was associated with externalizing behavioral difficulties in childhood in repeated SDQ measures at 7 and 11 years. The slight mediating effects of maternal thyroid hormones in early gestation warrant further evaluation.

Project description:IntroductionMaternal hypothalamic-pituitary-adrenal (HPA) axis disruption in pregnancy may contribute to the programming of childhood respiratory disease and may modify the effect of chemical toxins, like lead (Pb), on lung development. Child sex may further modify these effects. We sought to prospectively examine associations between maternal HPA axis disruption, prenatal Pb and childhood lung function and explore potential effect modification by maternal cortisol and child sex on the association between prenatal Pb and lung function outcomes.Materials and methodsAnalyses included 222 mothers and children enrolled in a longitudinal birth cohort study in Mexico City. Maternal diurnal salivary cortisol was assessed in pregnancy; cortisol awakening response (CAR) and diurnal slope were calculated. Blood Pb was measured during the second trimester of pregnancy. Post-bronchodilator lung function was tested at ages 8-11 years. Associations were modeled using generalized linear models with interaction terms, adjusting for covariates.ResultsA higher (flatter) diurnal slope was associated with lower FEV1/FVC ratio (β: 0.433, 95%CI [-0.766, -0.101]). We did not find any main effect associations between prenatal Pb and lung function outcomes. We report an interaction between Pb and cortisol in relation to FEV1/FVC and FEF25-75% (pinteraction<0.05 for all). Higher prenatal Pb was associated with reduced FEV1/FVC only in children whose mothers had a high CAR. Higher prenatal Pb was also associated with reduced FEV1/FVC and FEF25-75% in mothers with a flatter diurnal slope. A 3-way interaction between prenatal Pb, CAR and sex on FEV1/FVC, indicated that boys born to women with high CAR and higher prenatal Pb levels had lower FEV1/FVC ratios (pinteraction = 0.067).ConclusionsAssociations between prenatal Pb and childhood lung function were modified by disrupted maternal cortisol in pregnancy and child sex. These findings underscore the need to consider complex interactions to fully elucidate effects of prenatal Pb exposure on childhood lung function.

Project description:BackgroundMaternal and neonatal thyroid function is critical for growth and neurodevelopment. Exposure to individual per- and polyfluoroalkyl substances (PFAS) can alter circulating thyroid hormone levels, but few studies have investigated effects of combined exposure to multiple PFAS.ObjectivesEstimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function.MethodsThe study population consisted of 726 mothers and 465 neonates from Project Viva, a Boston, Massachusetts area longitudinal pre-birth cohort. We measured six PFAS [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido)acetate (EtFOSAA), and 2-(N-methyl-perfluorooctane sulfonamido)acetate (MeFOSAA)] and thyroxine (T4), Free T4 Index (FT4I), and thyroid stimulating hormone (TSH) in maternal plasma samples collected during early pregnancy, and neonatal T4 in postpartum heel sticks. We estimated individual and joint effects of PFAS exposure with thyroid hormone levels using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), and evaluated potential non-linearity and interactions among PFAS using BKMR.ResultsHigher concentrations of the PFAS mixture were associated with significantly lower maternal FT4I, with MeFOSAA, EtFOSAA, PFOA, and PFHxS contributing most to the overall mixture effect in BKMR and WQS regression. In infants, higher concentrations of the PFAS mixture were associated with lower T4 levels, primarily in males, with PFHxS and MeFOSAA contributing most in WQS, and PFHxS contributing most in BKMR. The PFAS mixture was not associated with maternal T4 or TSH levels. However, in maternal BKMR analyses, ln-PFOS was positively associated with T4 levels (Δ25th to 75th percentile: 0.21 µg/dL; 95% credible interval: -0.03, 0.47) and ln-PFHxS was associated with a non-linear effect on TSH levels.ConclusionsThese findings support the hypothesis that there may be combined effects of prenatal exposure to multiple PFAS on maternal and neonatal thyroid function, but the direction and magnitude of these effects may vary across individual PFAS.

Project description:BackgroundOver-the-counter analgesics during pregnancy or infancy may be related to neurobehavioural problems in children, but little is known about effects of different analgesic types, dosage, and timing.ObjectivesExamine associations of acetaminophen and ibuprofen use during pregnancy and infancy with executive function and behaviour problems in children.MethodsWe included 1225 mother-child pairs from Project Viva, a pre-birth cohort study. We assessed prenatal acetaminophen and ibuprofen use in early and mid-pregnancy and infant use in the first year of life using questionnaires. Parents and classroom teachers assessed child behaviours in mid-childhood (median 8 years), using the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ), with higher scores indicating worse functioning for both. We examined associations of acetaminophen and ibuprofen use during pregnancy and infancy with mid-childhood neurobehavioural outcomes using linear regression models adjusted for potential confounders.ResultsDuring pregnancy, 46.1% of mothers used acetaminophen ≥10 times and 18.4% used any ibuprofen. In the first year, 65.3% and 39.6% of infants received acetaminophen and ibuprofen ≥6 times, respectively. Higher (≥10 vs <10 times) prenatal acetaminophen (β 1.64 points; 95% confidence interval [CI] 0.59, 2.68) and any ibuprofen (β 1.56, 95% CI 0.19, 2.92) were associated with higher parent-rated BRIEF global scores. Patterns of association were linear across categories and were similar for other parent- and teacher-rated outcomes. Infancy exposure (≥6 vs <6 times) to acetaminophen (β 1.69, 95% CI 0.51, 2.87) and ibuprofen (β 1.40, 95% CI 0.25, 2.55) were associated with higher parent-rated BRIEF GEC scores but associations with teacher-rated scores were weaker.ConclusionsPrenatal and early-life exposure to acetaminophen and ibuprofen were associated with poorer executive function and behaviour in childhood. These findings highlight the need for further research on the mechanisms through which analgesics may act on fetal and child brain development.

Dataset Information

Prenatal lead exposure and childhood executive function and behavioral difficulties in project viva.

Publications

Prenatal lead exposure and childhood executive function and behavioral difficulties in project viva.

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