Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence

Background: Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. Objectives: To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. Methods: We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). Results: We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46–9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53–2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. Conclusions: We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.