There is accumulating evidence that exposure to toxicants in utero can have long-lasting consequences on child neurodevelopment. A number of recent studies have linked maternal prenatal urinary phthalate, BPA and organophosphate biomarkers to cognitive and behavioral abnormalities in children. Although these studies have been foundational in establishing the plausibility of these relations, none have been powered to evaluate clinically-confirmed behavioral phenotypes, since attention-deficit hyperactivity disorder (ADHD) is relatively rare and the previous studies have utilized relatively small birth cohorts. To address this gap in the literature, we propose a nested case-cohort study within the Norwegian Mother and Child Cohort (MoBa), a longitudinal birth cohort consisting of over 100,000 pregnancies, in order to investigate the relation between exposure to phthalate, BPA and organophosphate pesticide biomarkers and preschool ADHD. All clinically-confirmed cases of ADHD will be selected (n = 265), and a random sample of the cohort (n = 530) will be assembled to serve as the comparison group. By using the nested case-cohort design, we can both validly estimate the relative risk of ADHD and also examine the relationship between exposure and symptom severity continuously. A plausible pathway linking phthalate and BPA exposure to neurobehavioral outcomes is maternal thyroid hormone disruption. Thus we will also be investigating the relations between these biomarkers of exposure and maternal thyroid hormone function. Additionally, modification of the organophosphate-ADHD relation by functional gene variants in a key metabolism enzyme, PON1, will be examined. Finally, we will be incorporating sophisticated Bayesian models to handle multiple correlated exposures using state-of-the-art methodology.

Public Health Relevance

Pregnant women are passively exposed to countless environmental chemicals from the products they use and the food they eat. Some of these exposures have been found to cross the placenta;however, even without direct fetal exposure, offspring neurodevelopmental impairment could potentially be mediated by relatively minor disruptions in the maternal thyroid hormone system during pregnancy. There is an emerging literature linking certain toxicant exposures to gradients in behavioral symptoms;however, as of yet there is only weak evidence linking these exposures to a clinically-confirmed behavioral phenotype. This study will address this critical gap in the literature by elucidating the relationsip between select toxicant exposures and a well-defined behavioral endpoint, ADHD.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Gray, Kimberly A
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University of North Carolina Chapel Hill
Public Health & Prev Medicine
Schools of Public Health
Chapel Hill
United States
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Engel, Stephanie M; Villanger, Gro D; Nethery, Rachel C et al. (2018) Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort. Environ Health Perspect 126:057004
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Buckley, Jessie P; Doherty, Brett T; Keil, Alexander P et al. (2017) Statistical Approaches for Estimating Sex-Specific Effects in Endocrine Disruptors Research. Environ Health Perspect 125:067013
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Villanger, Gro Dehli; Learner, Emily; Longnecker, Matthew P et al. (2017) Effects of Sample Handling and Analytical Procedures on Thyroid Hormone Concentrations in Pregnant Women's Plasma. Epidemiology 28:365-369
Guidry, Virginia T; Longnecker, Matthew P; Aase, Heidi et al. (2015) Measurement of Total and Free Urinary Phenol and Paraben Concentrations over the Course of Pregnancy: Assessing Reliability and Contamination of Specimens in the Norwegian Mother and Child Cohort Study. Environ Health Perspect 123:705-11
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