Environmental Phthalate Exposure, Maternal Thyroid Function, and Birth Outcomes

Abstract

Preterm birth (< 37 completed weeks of gestation) and impaired fetal growth are among the most frequent causes of perinatal morality worldwide, and are associated with numerous long-term health consequences among surviving infants. While the causes of preterm birth and its consequences are complex and likely interrelated, characterization of potentially modifiable risk factors –such as those posed by environmental exposure to phthalates – may help diminish the substantial public health burden associated with these adverse pregnancy outcomes. Increasing scientific evidence suggests that exposure to phthalates during pregnancy may be associated with increased risks of deleterious birth outcomes such as preterm birth. Maternal endocrine disruption in gestation may be one pathway mediating some of these relationships. This dissertation research focuses on subclinical maternal thyroid hormone disruption as a potential biological pathway by which prenatal phthalate exposure influences adverse birth outcomes because (1) maintaining homeostatic maternal thyroid hormone levels throughout pregnancy is crucial for normal fetal growth and development; (2) few data are available on the direct effects of subclinical thyroid hormone changes in gestation on the risk of preterm birth; and (3) phthalate-associated thyroidal disturbances in pregnancy is a largely understudied area of environmental and reproductive epidemiology. In the first aim of this dissertation research, we observed that repeated measures of urinary phthalate metabolites were associated with altered maternal thyroid hormone levels in two qualitatively disparate populations of pregnant women in Northern Puerto Rico and Boston, MA. The second and third aims were conducted among the main dissertation cohort (a nested case-control study of preterm birth in Boston, MA), and explored the associations between subclinical changes in maternal thyroid function parameters and preterm birth as well as ultrasound and delivery indices of fetal growth. Our findings from Aim 2 suggest that subclinical alterations in individual maternal thyroid hormones, specifically free T4 (FT4) and total T3 (T3), influence the risk of preterm birth and the strength of these associations vary by gestational age. Additionally, we observed differences in the temporal hormonal patterns across gestation between women who delivered preterm and those who delivered at term, and these variations were most evident in the first trimester of pregnancy. Finally, our results from Aim 3 support findings from previous studies showing inverse associations between subclinical changes in FT4 and fetal growth indices including birth weight in generally euthyroid pregnant women. Overall, the public health implications of this research need to be determined. Additional human health and animal studies are required to confirm these observed relationships and to determine the potential biological mechanisms that underlie the effects of phthalate-induced thyroidal disturbances on pregnancy and birth outcomes.