Virissa Lenters1, Nina Iszatt2, Joan Forns3, Eliška Čechová4, Anton Kočan5, Juliette Legler6, Pim Leonards7, Hein Stigum8, Merete Eggesbø9. 1. Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway. Electronic address: Virissa.Lenters@fhi.no. 2. Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway. Electronic address: Nina.Iszatt@fhi.no. 3. Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway. Electronic address: joanfornsguzman@gmail.com. 4. Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice; 753/5, 625 00 Brno, Czech Republic. Electronic address: cechova@recetox.muni.cz. 5. Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice; 753/5, 625 00 Brno, Czech Republic. Electronic address: kocan@recetox.muni.cz. 6. Institute for Environmental Studies, VU University Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam, the Netherlands. Electronic address: j.legler@uu.nl. 7. Institute for Environmental Studies, VU University Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam, the Netherlands. Electronic address: pim.leonards@vu.nl. 8. Department of Non-Communicable Diseases, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway. Electronic address: Hein.Stigum@fhi.no. 9. Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway. Electronic address: Merete.Eggesbo@fhi.no.
Abstract
BACKGROUND: Numerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD. METHODS: We used a birth cohort of 2606 Norwegian mother-child pairs enrolled 2002-2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures. RESULTS: Breast milk concentrations of perfluorooctane sulfonate (PFOS) and β‑hexachlorocyclohexane (β-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p'‑Dichlorodiphenyltrichloroethane (p,p'-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise. CONCLUSIONS: In a multi-pollutant analysis of four classes of chemicals, early-life exposure to β-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p'-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.
BACKGROUND: Numerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD. METHODS: We used a birth cohort of 2606 Norwegian mother-child pairs enrolled 2002-2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures. RESULTS: Breast milk concentrations of perfluorooctane sulfonate (PFOS) and β‑hexachlorocyclohexane (β-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p'‑Dichlorodiphenyltrichloroethane (p,p'-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise. CONCLUSIONS: In a multi-pollutant analysis of four classes of chemicals, early-life exposure to β-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p'-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.
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