Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies.

INTRODUCTION: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. OBJECTIVE: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. METHODS: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. RESULTS: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. CONCLUSION: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444.

Prenatal and postnatal exposure to persistent organic pollutants and attention-deficit and hyperactivity disorder: a pooled analysis of seven European birth cohort studies.

Background: Attention-deficit/hyperactivity disorder (ADHD) is increasing worldwide for reasons largely unknown and environmental chemicals with neurotoxic properties, such as persistent organic pollutants (POPs), have been proposed to play a role. We investigated the association between prenatal and postnatal exposure to polychlorinated biphenyl-153 (PCB-153), p-p´-dichlorodiphenyldichloroethylene (p-p'-DDE) and hexachlorobenzene (HCB) and ADHD in childhood. Methods: We pooled seven European birth cohort studies encompassing 4437 mother-child pairs from the general population with concentrations of PCB-153, p-p´-DDE and HCB measured in cord blood, maternal blood or milk. We then calculated prenatal (birth) and postnatal (3, 6, 12 and 24 months) POP concentrations using a pharmacokinetic model. The operational definition of ADHD varied across cohorts and ranged from doctor diagnosis obtained from patient registries to maternal or teachers reports. We used multilevel (mixed) logistic regression models to estimate the associations between exposure to POPs at birth, 3, 6, 12 and 24 months and ADHD. Results: The global prevalence of ADHD in our study was 6%. The mean age at assessment of ADHD was 5.8 years (range: 3.8-9.5 years). We found no association between exposure to PCB-153, p-p´-DDE and HCB at any age point between birth and 24 months and ADHD, in the pooled analyses (pooled odds ratios ranging from 1.00 to 1.01). A number of sensitivity analyses gave basically the same results. Conclusions: In the largest study to date of 4437 children in seven European birth cohorts, we did not observe any association between either pre- or postnatal exposure (up to 24 months) to PCB-153, p-p´-DDE and HCB and the risk of ADHD before the age of 10 years.

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study.

BACKGROUND: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits. OBJECTIVES: We examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood. METHODS: We measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables. RESULTS: Blood concentrations (WHO2005-TEq) of Æ©PCDD/Fs ranged from 2.93-46.45 pg/g lipid base (median = 12.91 pg/g lipid base) and concentrations of Æ©PCBs were in the range of 1.24-25.47 pg/g lipid base (median = 6.85 pg/g lipid base) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (ß = -6.66, p < .05), in girls (ß = -10.98, p < .05) and, in one SRS subscale, in boys (ß = -6.86, p < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex. CONCLUSIONS: In an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed.