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Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: The HOME study.

ABSTRACT: To examine relationships between prenatal perfluoroalkyl substance (PFAS) exposure and adiposity in children born to women who lived downstream from a fluoropolymer manufacturing plant.Data are from a prospective cohort in Cincinnati, Ohio (HOME Study). Perfluorooctanoic (PFOA), perfluorooctane sulfonic (PFOS), perfluorononanoic (PFNA), and perfluorohexane sulfonic (PFHxS) acids were measured in prenatal serum samples. Differences were measured in body mass index z-scores (BMI), waist circumference, and body fat at 8 years of age (n = 204) and BMI between 2-8 years of age (n = 285) according to PFAS concentrations.Children born to women in the top two PFOA terciles had greater adiposity at 8 years than children in the 1st tercile. For example, waist circumference (cm) was higher among children in the 2nd (4.3; 95% CI: 1.7, 6.9) and 3rd tercile (2.2; 95% CI: -0.5, 4.9) compared to children in the 1st tercile. Children in the top two PFOA terciles also had greater BMI gains from 2 to 8 years compared to children in the 1st tercile (P < 0.05). PFOS, PFNA, and PFHxS were not associated with adiposity.In this cohort, higher prenatal serum PFOA concentrations were associated with greater adiposity at 8 years and a more rapid increase in BMI between 2-8 years.

SUBMITTER: Braun JM

PROVIDER: S-EPMC4688224 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: The HOME study.

Braun Joseph M JM Chen Aimin A Romano Megan E ME Calafat Antonia M AM Webster Glenys M GM Yolton Kimberly K Lanphear Bruce P BP

Obesity (Silver Spring, Md.) 20151111 1

<h4>Objective</h4>To examine relationships between prenatal perfluoroalkyl substance (PFAS) exposure and adiposity in children born to women who lived downstream from a fluoropolymer manufacturing plant.<h4>Methods</h4>Data are from a prospective cohort in Cincinnati, Ohio (HOME Study). Perfluorooctanoic (PFOA), perfluorooctane sulfonic (PFOS), perfluorononanoic (PFNA), and perfluorohexane sulfonic (PFHxS) acids were measured in prenatal serum samples. Differences were measured in body mass inde ...[more]

PMID: 26554535

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Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) are chemical substances spread throughout the environment worldwide. Exposure during pregnancy represents a specific window of vulnerability for child health.ObjectiveOur objective was to assess the impact of prenatal exposure to multiple PFAS on emotional and behavioral functions in 12-y-old children.MethodIn the PELAGIE mother-child cohort (France), prenatal exposure to nine PFAS was measured from concentrations in cord serum samples. Behavior was assessed at age 12 y using the parent-reported Strengths and Difficulties Questionnaire (SDQ) and the self-reported Dominic Interactive for Adolescents (DIA) for 444 children. Associations were estimated using negative binomial models for each PFAS. Bayesian kernel machine regression (BKMR) models were performed to assess the exposure mixture effect on children's behavior.ResultsIn our study population, 73% of mothers had spent more than 12 y in education. Higher scores on SDQ externalizing subscale were observed with increasing cord-serum concentration of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) [adjusted mean ratio (aMR)=1.18, 95% confidence interval (CI): 1.03, 1.34, and aMR=1.14 (95% CI: 1.00, 1.29) for every doubling of concentration, respectively]. Results for the hyperactivity score were similar [aMR=1.20 (95% CI: 1.04, 1.40) and aMR=1.18 (95% CI: 1.02, 1.36), respectively]. With regard to major depressive disorder and internalizing subscales, perfluorodecanoic acid (PFDA) was associated with higher self-reported DIA scores [aMR=1.14 (95% CI: 1.01, 1.27) and aMR=1.11 (95% CI: 1.02, 1.21), respectively]. In terms of the anxiety subscale, PFDA and PFNA were associated with higher scores [aMR=1.11 (95% CI: 1.02, 1.21) and aMR=1.10 (95% CI: 1.01, 1.19), respectively]. Concurrent increases in the PFAS concentrations included in the BKMR models showed no change in the SDQ externalizing and DIA internalizing subscales scores.ConclusionPrenatal exposure to PFNA and PFOA were associated with increasing scores for measures of externalizing behaviors, specifically hyperactivity. We also identified associations between PFNA and PFDA prenatal exposure levels and increasing scores related to internalizing behaviors (general anxiety and major depressive disorder), which adds to the as yet sparse literature examining the links between prenatal exposure to PFAS and internalizing disorders. https://doi.org/10.1289/EHP12540.

Project description:BackgroundDNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.ObjectivesWe examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio).MethodsWe quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations.ResultsAfter adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children's age.DiscussionIn these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118.

Dataset Information

Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: The HOME study.

Publications

Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: The HOME study.

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