Congenital Cytomegalovirus Infection in Fetal Demise: A Retrospective Cohort Study

Background: CMV is the most common congenital infection worldwide, affecting 0.2–6% of live births and causing significant morbidity and mortality. Although most infections are asymptomatic, severe cases can lead to fetal demise. Objective: To quantify and characterize confirmed CMV infection among fetal demises in a large pediatric hospital in the US from 2013 to 2024. Methods: A retrospective electronic health record (EHR) review of pregnancies with CMV testing, delivery summaries, and confirmed fetal CMV infection via tissue or autopsy linkage. Results: During the review period, 61,973 pregnancies were recorded, with 1173 resulting in fetal demise. Among 1670 pregnancies tested for CMV, 859 had positive testing (e.g., CMV IgG, CMV IgM, CMV DNA), including 96 demises, 94 (11%) of which we had complete delivery records. Four (4%) of these fetal demises were directly attributable to CMV based on positive CMV testing from amniocentesis, fetal tissue, or placenta. Most demises occurred in the second or third trimester (mean gestational age 28.4 ± 6.6 weeks), while the four CMV-attributable cases averaged 23.7 ± 3.7 weeks. Among 93 fetal demise pregnancies in which maternal CMV IgM testing was performed, 9 (9.7%) had a positive CMV IgM result. All confirmed CMV-attributable fetal demises occurred among these CMV IgM-positive pregnancies. Conclusion: These findings underscore CMV’s role in perinatal mortality and highlight the need for improved screening and prevention strategies.