Dataset Information

Prenatal exposure to per- and polyfluoroalkyl substances in association with autism spectrum disorder in the MARBLES study.

ABSTRACT:

Background

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has shown potential to adversely affect child brain development, but epidemiologic evidence remains inconsistent. We examined whether prenatal exposure to PFAS was associated with increased risk of autism spectrum disorder (ASD).

Methods

Participants were 173 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD cohort. At 3 years old, children were clinically confirmed for ASD and classified into ASD (n = 57) and typical development (TD, n = 116). We quantified nine PFAS in maternal serum collected during pregnancy. We examined associations of ASD with individual PFAS as well as the combined effect of PFAS on ASD using scores of the first principal component (PC-1) accounting for the largest variance.

Results

Prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) showed positive associations (per 2 nanogram per milliliter increase: relative risk (RR) = 1.20, 95% CI: 0.90, 1.61 [PFOA]; RR = 1.24, 95% CI: 0.91, 1.69 [PFNA]), while perfluorohexane sulfonate (PFHxS) showed a negative association (RR = 0.88, 95% CI: 0.77, 1.01) with ASD risk. When examining associations of ASD with untransformed PFAS concentrations, PFOA, PFNA, and PC-1 were associated with increased ASD risk (per nanogram per milliliter increase: RR = 1.31, 95% CI: 1.04, 1.65; RR = 1.79, 95% CI: 1.13, 2.85; RR = 1.10, 95% CI: 0.97, 1.25, respectively), while the RR of PFHxS moved toward the null.

Conclusions

From this high-risk ASD cohort, we observed increased risk of ASD in children exposed to PFOA and PFNA. Further studies should be conducted in the general population because this population may have a larger fraction of cases resulting from genetic sources.

SUBMITTER: Oh J

PROVIDER: S-EPMC7856021 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background/objectivePer- and polyfluoroalkyl substances (PFAS) display neurobehavioral toxicity in laboratory animal studies. We examined associations of modeled prenatal maternal exposure to PFAS with child diagnosis of autism spectrum disorder (ASD).MethodsParticipants were 453 mother-child pairs from CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based case-control study. Children underwent psychometric testing and were clinically confirmed for ASD (n = 239) or typical development (TD, n = 214). At the end of the clinic visit, maternal blood specimens were collected. We quantified nine PFAS in maternal serum samples collected when their child was 2-5 years old. As surrogate in utero exposure, we used a model built from external prospective data in pregnancy and 24 months post-partum and then reconstructed maternal PFAS serum concentrations during pregnancy in this case-control sample. We used logistic regression to evaluate associations of modeled prenatal maternal PFAS concentrations with child ASD.ResultsModeled prenatal maternal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were borderline associated with increased odds of child diagnosis of ASD (per nanogram per milliliter increase: odds ratio [OR] = 1.46; 95% confidence interval [CI]: 0.98, 2.18 for PFHxS, OR = 1.03; 95% CI: 0.99, 1.08 for PFOS). When compared to the lowest quartile (reference category), the highest quartile of modeled prenatal maternal PFHxS was associated with increased odds of child diagnosis of ASD (OR = 1.95; 95% CI: 1.02, 3.72).ConclusionsIn analyses where modeled prenatal maternal PFAS serum concentrations served as in utero exposure, we observed that prenatal PFHxS and PFOS exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD. Further studies in which PFAS concentrations are prospectively measured in mothers and children at a range of developmental stages are needed to confirm these findings.

Project description:BackgroundEvidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD.MethodsWe quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD longitudinal cohort. At 3?years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n?=?46), non-typical development (Non-TD, n?=?55), and typical development (TD, n?=?100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD.ResultsMost associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR)?=?1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR?=?0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR?=?0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR?=?0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR?=?5.09; 95% CI: 2.05, 12.6), MCOP (RRR?=?1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR?=?3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (?DEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null.ConclusionsOur study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings.

Project description:BACKGROUND:Per- and polyfluoroalkyl substances (PFASs) are suspected developmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We examined associations of prenatal and childhood PFAS exposure with performance on assessments of cognition in children. METHODS:We included mother-child pairs from Project Viva, a longitudinal Boston-area birth cohort enrolled during 1999-2002. We quantified concentrations of eight PFASs, including perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS), in plasma collected from women during pregnancy (median 9.7?weeks gestation) and from children at a visit in mid-childhood (median age 7.7?years). In early childhood (median age 3.2?years) we administered standardized assessments of visual motor skills and vocabulary comprehension, and in mid-childhood we assessed visual motor skills, visual memory, and verbal and non-verbal intelligence. Using multivariable regression, we estimated associations of prenatal and childhood PFAS plasma concentrations with children's cognitive assessment scores, adjusted for relevant covariates including breastfeeding, maternal intelligence, parental education, and household income. Samples sizes ranged from 631 to 971, depending on analysis. RESULTS:Prenatal PFAS concentrations were associated with both better and worse cognitive performance; children with top quartile prenatal concentrations of some PFASs had better visual motor abilities in early childhood and non-verbal IQ and visual memory in mid-childhood, while children with upper quartile prenatal PFOA and PFOS had lower mid-childhood visual-motor scores. In cross-sectional analyses of mid-childhood PFAS concentrations and cognitive assessments, visual-motor scores on the Wide Range Assessment of Visual Motor Abilities (WRAVMA) (standardized mean?=?100, standard deviation?=?15) were lower among children with higher PFHxS (fourth quartile (Q4) vs. Q1: -5.0, 95% confidence interval (CI): -9.1, -0.8). Upper quartiles of childhood PFOA and PFOS were also associated with somewhat lower childhood WRAVMA scores, but childhood PFASs were not associated with verbal or non-verbal IQ or visual memory. CONCLUSIONS:We present evidence suggesting associations of prenatal and childhood PFAS exposure with lower childhood visual motor abilities. Other results were inconsistent, with higher prenatal PFASs associated in some cases with better cognitive outcomes.

Project description:Background/objectivePer- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal serum PFAS concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood.MethodsWe included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson regression models to estimate associations expressed as relative risks (RR).ResultsAmong six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (β = -5.22, 95% CI: -8.27, -2.17) and 36 months of age (β = -5.18, 95% CI: -9.46, -0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03).ConclusionsPrenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.

Project description:ImportanceThe etiology of autism spectrum disorder (ASD) is poorly understood, but prior studies suggest associations with airborne pollutants.ObjectiveTo evaluate the association between prenatal exposures to airborne pollutants and ASD in a large population-based cohort.Design, setting, and participantsThis population-based cohort encompassed nearly all births in Metro Vancouver, British Columbia, Canada, from 2004 through 2009, with follow-up through 2014. Children were diagnosed with ASD using a standardized assessment with the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter less than 2.5 µm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2) at the maternal residence during pregnancy were estimated with temporally adjusted, high-resolution land use regression models. The association between prenatal air pollution exposures and the odds of developing ASD was evaluated using logistic regression adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018.ExposuresMean monthly concentrations of ambient PM2.5, NO, and NO2 at the maternal residence during pregnancy, calculated retrospectively using temporally adjusted, high-resolution land use regression models.Main outcomes and measuresAutism spectrum disorder diagnoses based on standardized assessment of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The hypothesis being tested was formulated during data collection.ResultsIn a cohort of 132 256 births, 1307 children (1.0%) were diagnosed with ASD by the age of 5 years. The final sample size for the PM2.5-adjusted model was 129 439 children, and for NO and NO2, it was 129 436 children; of these, 1276 (1.0%) were diagnosed with ASD. Adjusted odds ratios for ASD per interquartile range (IQR) were not significant for exposure to PM2.5 during pregnancy (1.04 [95% CI, 0.98-1.10] per 1.5 μg/m3 increase [IQR] in PM2.5) or NO2 (1.06 [95% CI, 0.99-1.12] per 4.8 ppb [IQR] increase in NO2) but the odds ratio was significant for NO (1.07 [95% CI, 1.01-1.13] per 10.7 ppb [IQR] increase in NO). Odds ratios for male children were 1.04 (95% CI, 0.98-1.10) for PM2.5; 1.09 (95% CI, 1.02-1.15) for NO; and 1.07 (95% CI, 1.00-1.13) for NO2. For female children, they were for 1.03 (95% CI, 0.90-1.18) for PM2.5; 0.98 (95% CI, 0.83-1.13) for NO; and 1.00 (95% CI, 0.86-1.16) for NO2.Conclusions and relevanceIn a population-based birth cohort, we detected an association between exposure to NO and ASD but no significant association with PM2.5 and NO2.

Project description:BackgroundPrenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that faster growth in early infancy may be associated with maternal PFAS concentrations.MethodsAmong 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5 months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression.ResultsAssociations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5-1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5 months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (-0.26 SD per ln-ng/mL PFOS, 95% CI -0.43, -0.10; -0.17 SD per ln-ng/mL PFHxS, 95% CI -0.33, -0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio [OR] 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations.DiscussionWe observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass.

Project description:BackgroundPregnant women are ubiquitously exposed to per- and polyfluoroalkyl substances (PFAS). Prenatal exposure to PFAS has been associated with lower birth weight but also with excess adiposity and higher weight in childhood. These mixed findings warrant investigation of the relationship between PFAS and dynamic offspring growth.ObjectivesTo investigate the association between prenatal PFAS exposure and early-life growth trajectories during the first 2 y.MethodsPregnant women (n=3,426) were recruited from 2013 to 2016 from the Shanghai Birth Cohort (SBC) Study, and their children were followed up from birth to 2 y of age. Seven PFAS congeners were quantified in pregnant women's serum during the first trimester. Our study population was restricted to 1,350 children who had five repeated measurements for at least one anthropometric measure. Four anthropometric measures, including weight, length/height, weight-for-length, and head circumference, were evaluated at birth, 42 d, 6 months, 12 months, and 24 months, and standardized into z-scores using the World Health Organization reference. Trajectories of each measure were classified into five groups using group-based trajectory modeling. Multinomial logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for trajectory groups according to log2-transformed PFAS concentrations, and the moderate-stable group was selected as the reference group for all measures.ResultsHigher prenatal exposure to PFAS was associated with elevated odds for the low-rising weight-for-age z-score (WAZ) trajectory, and the high-rising length-for-age z-score (LAZ) trajectory. Meanwhile, PFAS levels were associated with decreased odds for the low-rising and high-rising weight-for-length z-score (WLZ) trajectories. In addition, the associations of PFAS with growth trajectory groups differed by sex, where males had greater odds for the low-rising and low-stable WAZ trajectories and for the high-stable and low-rising WLZ trajectories. In contrast, inverse associations were consistently observed with trajectories of the high-stable, low-stable, and low-rising head-circumference-for-age z-score (HCZ) in relation to most individual PFAS congeners. PFAS mixtures analysis further confirmed the above findings.DiscussionTrajectory analysis approach provided insight into the complex associations between PFAS exposure and offspring growth. Future studies are warranted to confirm the present findings with trajectory modeling strategies and understand the clinical significance of these trajectory groups. https://doi.org/10.1289/EHP9875.

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.