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Abstract Body

Background: Infants are exposed to a cocktail of environmental chemicals during the critical
window of neurodevelopment. Yet, the potential role of persistent environmental chemicals in
neurodevelopmental disorders is understudied and inconclusive. Attention-deficit/hyperactivity
disorder (ADHD) is increasing worldwide, for reasons largely unknown. We investigated the
association between exposure to some important persistent environmental chemicals and ADHD in
childhood, in several separate studies.
Methods: First, we used a subset of 1199 mother- child pairs oversampled for
neurodevelopmental outcomes from the Norwegian HUMIS study. Twenty-seven persistent POPs
(14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flameretardants, and
perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured. Then we used
a collaborative study of nine European population-based datasets, encompassing 4,826 mother–child
pairs where PFOA and PFOS were measured. Finally, we studied the concentrations of PCB-153,
pp-DDE, HCB and ADHD in seven European birth cohort studies encompassing 4437 mother–child
pairs. We estimated postnatal exposures in the first 2 years of life using a validated pharmacokinetic
model, used multiple imputation for missing covariates, and used ordinary logistic regression and
elastic net penalized 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 metaanalysis.
Confounders were identified by Directed Acyclic Graphs (DAGs)
Results: The prevalence of ADHD ranged from 2.3% to 7.3% Breastmilk concentrations of
PFOS and β-hexachlorocyclohexane (β-HCH) were associated with increased risk of doctordiagnosed
ADHD in the HUMIS study (OR 1.77; 95% CI 1.16-2.72 and OR, 1.75 CI 1.22-2.53, per
interquartile range increase in ln-transformed concentrations, respectively). Stronger associations
were observed among girls than boys for PFOS. No overall association was observed in the
collaborative study for PFOS and PFOA, however, we observed sex-specific effects also here.
Specifically, girls were more sensitive to PFAS across studies. No association was observed between
the other measured toxicants, measured in the second collaborative study, and ADHD.
Conclusions: Children born to mothers with higher body burdens of perfluorinated
chemicals, have increased risk of an ADHD diagnosis at school age. Girls may be especially
sensitive to the neurotoxic effects of these chemicals. Perfluorinated chemicals are found in Teflon,
Gortex and non-sticking food containers amongst others and have very long half-lives in the
environment and in our bodies.