Association Between Maternal Cytomegalovirus Seropositivity, Preterm Birth, and Preeclampsia in Two Cohorts From Quebec, Canada: A Mediation Analysis

Abstract

Problem: Preterm birth and preeclampsia significantly contribute to infant morbidity and mortality, posing critical public health concerns. Viral infections, particularly Cytomegalovirus (CMV), associated with chronic inflammation, may play a role in these adverse pregnancy outcomes. The contribution of CMV to preterm birth and preeclampsia requires further investigation.

Method of study: Data from 6048 pregnant women from two prospective Quebec cohorts, recruited between May 2005 and August 2012, were analyzed. First-trimester CMV serology was the exposure variable. Associations were assessed using multivariable logistic regression adjusted by inverse probability treatment weighting (IPTW) of propensity scores. Mediation analyses estimated the direct effect of maternal CMV serostatus on preterm birth, excluding mediation by preeclampsia.

Results: Preterm birth and preeclampsia proportions were 5.1% (95% CI: 4.6-5.7) and 1.9% (95% CI: 1.6-2.3), respectively. Multivariable logistic regression adjusted by IPTW showed associations between CMV seropositivity and preterm birth (OR 1.20, 95% CI: 1.02-1.41) and CMV seropositivity and preeclampsia (OR 1.41, 95% CI: 1.08-1.84). Mediation analysis indicated that 97% of the total effect of CMV seropositivity on preterm birth is direct, with the remaining 3% mediated by preeclampsia.

Conclusions: CMV seropositivity appears to be a risk factor for both preterm birth and preeclampsia. The effect of maternal CMV seropositivity on preterm birth is primarily direct, not mediated by preeclampsia. Future studies should explore the impact of preventive measures against CMV infection on the incidence of preterm delivery and preeclampsia.

Keywords: cytomegalovirus; mediation analysis; preeclampsia; pregnancy; preterm birth.