Understanding the Relationship Between Maternal Thyroid Hormones and Neurodevelopmental Outcomes

Abstract

Background: In utero exposures to endocrine disrupting chemicals can impact a range of health outcomes for the offspring. Specifically, when considering potential disruptions to proper maternal thyroid functioning due to chemical exposures there is increasing concern that adverse neurodevelopmental outcomes may occur in the offspring. A preclinical outcome, hypothyroxinemia (low free thyroxine and thyroid stimulating hormone within the reference rage) is being recognized as a potential outcome of interest in understanding alterations in maternal thyroid functioning. Methods: A literature review on the associations between maternal thyroid hormone levels, including maternal hypothyroxinemia and offspring neurodevelopmental outcomes was conducted. Studies were categorized if the main analysis presented evaluated the risk of adverse neurological outcomes as a result of incremental changes in maternal fT4 or the categorical outcome of yes/no hypothyroxinemia. Results: We found that altered free thyroxine (fT4) in early pregnancy has the most evidence regarding the relationship between altered maternal thyroid hormone homeostasis and adverse neurodevelopmental outcomes in offspring. We will present multiple approaches to utilize data from the literature to evaluate the magnitude of impact from altered maternal fT4 levels on offspring neurodevelopment. These approaches consist of both evaluating dose-response relationships between maternal fT4 and offspring neurodevelopment and examining how shifts in distributions of thyroid hormone levels may place additional proportions of a population at risk. Conclusions: The presented methods can be used to assess the potential neurodevelopmental impacts on the fetus of a pregnant mother exposed to a chemical that may potentially alter homeostatic thyroid functioning (e.g., PCBs, perchlorate, PBDEs, PFAs, BPA)