Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort

Abstract

Background:Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited.Objectives:We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children.Methods:Among 83,389 mother–child pairs enrolled in the Danish National Birth Cohort during 1996–2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child’s sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights.Results:Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother’s PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise.Conclusions:In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.Citation:Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei CY, Bossi R, Henriksen TB, Bonefeld-Jørgensen EC, Olsen J. 2015. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case–control study in the Danish National Birth Cohort. Environ Health Perspect 123:367–373; http://dx.doi.org/10.1289/ehp.1408412

Behavioral difficulties in 7-year old children in relation to developmental exposure to perfluorinated alkyl substances

“…Consistent with the present findings, previous investigations showed no association between prenatal exposure to PFASs and child neurodevelopment (Fei and Olsen 2011; Liew et al 2015; Ode et al 2014; Stein et al 2013; Stein et al 2014). Previous studies of postnatal PFAS exposures and child neurodevelopment are inconsistent, but most were based on cross-sectional designs (Gump et al 2011; Hoffman et al 2010; Stein and Savitz 2011) with methodological limitations, such as unmeasured confounders and the potential for reverse causation.…”

“…The maternal PFAS concentrations in our cohort were higher than previously reported levels in some other populations (Hoyer et al 2015), but comparable to those reported from Denmark (Liew et al 2015). The concentrations in children appeared to decrease over time for PFOS and somewhat for PFHxS, but tended to increase for other PFASs.…”

“…So far, published results from prospective cohort studies have revealed little evidence of PFAS neurotoxicity. Indeed, maternal serum PFAS concentrations were not associated with behavioral problems, including attention deficit/hyperactivity disorder and autism, in children aged 7 to 13 years from the Danish National Birth Cohort (Fei and Olsen 2011; Liew et al 2015). In addition, studies conducted among children from the C8 Health Project showed no associations between estimated in utero and measured childhood PFOA concentrations and neuropsychological test scores (Stein et al 2013).…”

Early-life exposure to EDCs: role in childhood obesity and neurodevelopment

“…172 Several studies report protective or null associations between prenatal PFAS exposure and child neurobehavior. 64,165–167,169,173 …”

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

“…3). Such chemicals may interfere with thyroid function (69), and they have also been considered risk factors for neurodevelopmental disorders in the offspring (70). Finally, psychiatric disease in the parents may introduce confounding (Fig.…”