Metal Exposure During Pregnancy: Trends, Predictors, Associations with Birth Outcomes and the Modifying Effect of Maternal Psychosocial Stress

Abstract

Preterm birth is a significant public health concern as a leading cause of infant mortality; it also contributes substantially to childhood and adult morbidity. Other adverse birth outcomes including low birthweight are associated with later comorbidities. There is growing evidence that the underlying contributors to adverse birth outcomes may include environmental contaminants (like metals), but these factors are understudied. Puerto Rico has one of the highest preterm birth rates of all U.S. states and territories. Moreover, the population in Puerto Rico is exposed to higher levels of many environmental chemicals because of heavily contaminated hazardous industrial sites. Even though prenatal exposure to heavy metals has been well investigated, our knowledge of the threats to the fetus at low levels of exposure remains rather limited. From animal studies, few data are available on the effects of excessive exposure from essential trace elements on adverse pregnancy outcomes. As humans are continuously exposed to a mixture of environmental toxicants, and typically not to single agents in isolation, there is a pressing need to study the relationship of exposures both individually and as mixtures. This dissertation investigates the predictors of environmental metal exposures among pregnant women, and the potential of metal exposures measured in different media to increase the risk of adverse birth outcomes. The interactions between psychosocial stress and the exposure biomarkers on adverse birth outcomes are also explored.

The four aims of this dissertation examine a subset of participants from the “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)” cohort. Aim 1 of this dissertation identifies levels, trend, and predictors of prenatal exposure for 14 metals. Aim 2 investigates the individual and collective effects of metals on adverse birth outcomes. Of all the metals assessed, blood lead at low levels, and potentially below current reference levels, was the most strongly associated with increased risk of preterm birth and decreased gestational length. Findings in Aim 2 also showed that lead, zinc, and manganese may contribute to adverse birth outcomes. Aim 3 explores the modifying effect of maternal psychosocial stress on the association between the metal exposure biomarkers and adverse birth outcomes. Presence of “poor” psychosocial status strengthened the adverse associations between Mn and preterm birth, indicating that prenatal psychosocial stress may modify vulnerability to metal exposure. Finally, Aim 4 examines the mixture predictive performance of urine and blood metal biomarkers, and integrated multimedia biomarkers incorporating both matrices, in association with preterm birth. Metal mixtures measured in urine (specific gravity corrected), blood, and integrated biomarkers had comparable performance in associations with preterm birth, indicating that using urine or blood may be an equally good approach to evaluate the metals as a mixture, but only when urine measurements of metal account for urinary dilution.

Overall, these results broaden our understanding of the effects of metal mixtures on birth outcomes. We identify dietary and behavioral predictors of metal exposures which could inform exposure reduction strategies, and potentially result in an eventual reduction in preterm birth rates. Furthermore, our novel study design underscores the importance of considering the performance of exposure biomarkers measured in different media, and modifying effects of non-chemical exposures, when evaluating the relationship between chemical exposures and birth outcomes. Further studies are needed to substantiate these findings to advance our knowledge on the impact of environmental chemicals on pregnancy.