The Impact of Environmental Heavy Metal Exposures on Pregnancy and Birth Outcomes

Abstract

Background: There is still a paucity of information on maternal biological mechanisms specific to adverse birth outcomes despite maternal environmental exposure and health status being known to influence neonatal morbidity and mortality. The purpose of this study was to explore maternal biomarkers pertinent to infant development in utero, specifically matrix metalloproteinases (MMPs), and determine their relationships to environmental heavy metals such as arsenic, cadmium, lead, mercury, and manganese as well as their relationships to outcomes such as preterm birth, low birth weight and small for gestational age infant outcomes. Methods: A secondary data analysis on 1533 mother-infant pairs from the Maternal and Infant Research on Environmental Chemicals (MIREC) cohort was conducted to statistically test relationships between metals and biomarkers, as well as biomarkers and outcome. A systematic literature review and meta-analysis was also conducted to identify the interdependencies between maternal blood biomarkers relating to adverse pregnancy outcomes. Results: Multivariate regression models were used to estimate odds ratios (OR) for the association between metal concentrations in quartiles and both high (90%) and low (10%) maternal MMP levels. Significant metal-related effects were observed with different MMP responses. A total of 54 studies (35 for meta-analysis), including 43,702 women and evaluating 50 biomarkers, met the inclusion criteria and all subgroups of biomarkers showed significant associations with birth outcomes with no apparent publication bias. Conclusions: Maternal plasma markers may serve as potentially valuable tools in the investigation of maternal molecular mechanisms, especially select toxicity pathways underlying metal-mediated adverse infant outcomes. Further research is still needed to evaluate biomarkers such as proteomic and genetic profiles in other various maternal biological samples.