Exposure to Toxic Metals and Per- and Polyfluoroalkyl Substances and the Risk of Preeclampsia and Preterm Birth in the United States: a Review

Preeclampsia and preterm birth are among the most common pregnancy complications and are the leading causes of maternal and fetal morbidity and mortality in the United States. Adverse pregnancy outcomes are multifactorial in nature and increasing evidence suggests that the pathophysiology behind preterm birth and preeclampsia may be similar-specifically, both of these disorders may involve abnormalities in placental vasculature. A growing body of literature supports that exposure to environmental contaminants in the air, water, soil, and consumer and household products serves as a key factor influencing the development of adverse pregnancy outcomes. In pregnant women, toxic metals have been detected in urine, peripheral blood, nail clippings, and amniotic fluid. The placenta serves as a "gatekeeper" between maternal and fetal exposures, because it can reduce or enhance fetal exposure to various toxicants. Proposed mechanisms underlying toxicant-mediated damage include disrupted placental vasculogenesis, an up-regulated proinflammatory state, oxidative stressors contributing to prostaglandin production and consequent cervical ripening, uterine contractions, and ruptured membranes and epigenetic changes that contribute to disrupted regulation of endocrine and immune system signaling. The objective of this review is to provide an overview of studies examining the relationships between environmental contaminants in the US setting, specifically inorganic (eg, cadmium, arsenic, lead, and mercury) and organic (eg, per- and polyfluoroalkyl substances) toxicants, and the development of preeclampsia and preterm birth among women in the United States.