Fetal growth in environmental epidemiology: mechanisms, limitations, and a review of associations with biomarkers of non-persistent chemical exposures during pregnancy

Background Non-persistent chemicals, such as phthalates, environmental phenols, organophosphate pesticides, and others, are challenging to study because of their ubiquity in the environment, diverse exposure routes, and high temporal variability of biomarkers. Nonetheless, there is interest in understanding how gestational exposure to these chemicals may affect fetal growth, as perturbations to normal fetal growth are related to a plethora of adverse health outcomes in childhood and adulthood. Methods The purpose of this review is to describe the state of the science on this topic. We searched PubMed for studies that included both 1) biomarkers of non-persistent chemicals collected during pregnancy and 2) fetal growth outcomes measured at birth (e.g., birth weight) or by ultrasound in utero (e.g., estimated fetal weight). Results The bulk of the literature we found uses biomarkers measured at a single time point in pregnancy and birth weight as the primary measure of fetal growth. There is a small, but growing, body of research that uses ultrasound measures to assess fetal growth during pregnancy. In addition to summarizing the findings of the publications we identified, we describe inconsistencies in methodology, areas for improvement, and gaps in existing knowledge that can be targeted for improvement in future work. This literature is characterized by variability in methodology, likely contributing to the inconsistency of results reported. We further discuss maternal, placental, and fetal pathways by which these classes of chemicals may affect fetal growth. Conclusions To improve understanding of how everyday chemical exposures affect fetal growth, and ultimately lifelong health outcomes, mechanisms of toxicant action should be considered alongside improved study designs for future hypothesis-driven research.