Investigations Into the Effects of Gestational Exposure to Environmental Phthalates on Maternal and Perinatal Outcomes and the Role of Inflammation Biomarkers as Potential Mediators

Abstract

Objectives The aims of this thesis were to (1) investigate the association of gestational exposure to environmental phthalates with maternal and perinatal outcomes, and (2) explore phthalate-induced changes to maternal inflammatory responses as potential mediators of possible health effects. Methods A systematic review was performed to summarize existing evidence on the association of gestational exposure to phthalates with obstetrical outcomes, including pre-eclampsia (PE), pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), birth weight (BW), head circumference (HC), gestational age (GA), preterm birth (PB), and Apgar scores (AS). Additionally, a secondary analysis of data from the MIREC Study was conducted to evaluate the association of phthalate metabolites with clinical outcomes in the mother and infant using multiple linear and logistic regression, and with inflammatory biomarkers using multinomial logistic regression. Results The systematic review identified a total of 24 articles, and observed inconsistent evidence on BW, HC, GA, and PB, a paucity of research on IUGR, PE, GDM, and AS, and a lack of studies on PIH. However, among studies with statistically significant (p<0.05) results, most suggest an association of phthalates with decreased BW and GA, and increased HC and PB. Findings from the MIREC Study indicate a significant (p<0.01) positive association between MBP and HC among female infants; however, null results were identified for BW, GA, PB, AS, and PIH. In relation to the exposure to phthalates, general trends among suggestive associations (p<0.05) for head circumference showed consistent increases in females and decreases in males, and for gestational age displayed decreases in both stratums. Additionally, a significant positive association of MBzP and ∑DEHP was observed with high MMP-2 and low VCAM levels, respectively. Results approaching statistical significance demonstrated a positive association of ∑DEHP with low MCP1 and ICAM levels, MCPP with low GMCSF levels, MBzP with low CRP and high ICAM levels, and MEP with high MMP-7 and IL-2 levels. Conclusion From the systematic review, the effects of phthalates on maternal and perinatal health remain unclear, possibly due to sources of heterogeneity and challenges in exposure assessment. In the MIREC Study cohort, phthalate levels were associated with GA and HC in infants in a sex-specific manner. Phthalates also appear to influence the circulating inflammatory marker levels, possibly explaining the observed adverse effects. Future research is needed to validate these findings.