The Spectrum of Placental Findings of First-Trimester Cytomegalovirus Infection Related to the Presence of Symptoms in the Newborns and Stillbirths.

Abstract

Cytomegalovirus (CMV) is one of the most common congenital infections worldwide and a leading cause of prenatal neurological disorders, sensorineural hearing loss, and stillbirth. The placental factors involved in CMV transmission from mother to fetus remain poorly understood. We aimed to evaluate the histopathological placental findings associated with first-trimester CMV infection in relation to stillbirth and symptomatic presentation in newborns. This retrospective case-control study analyzed pregnancies with confirmed first-trimester CMV infection followed at 2 tertiary referral hospitals between 2012 and 2024. Symptomatic newborns were compared with asymptomatic newborns and stillbirths. Univariate statistical analyses were performed. A total of 40 placentas were included: 23 from asymptomatic newborns, 11 from symptomatic newborns, and 6 from stillbirths. Compared with asymptomatic cases, placentas from symptomatic newborns were smaller and showed increased chronic plasma cell deciduitis, chronic villitis (without avascular villi, breakdown villi, necrosis, or hemosiderin deposits), more CMV inclusions in fibroblasts, and higher rates of positive CMV immunostaining. Stillbirth placentas exhibited more severe chronic villitis (with avascular villi, breakdown villi, necrosis, and hemosiderin deposits), more extensive intervillous fibrin deposition, CMV inclusions in endothelial and trophoblastic cells, and higher frequencies of maternal and fetal vascular malperfusion compared with placentas from symptomatic newborns. Ultrasound screening did not appear to be a reliable predictor of placental involvement in first-trimester CMV infection. Greater involvement of the villous and vascular barriers-both direct and indirect-was associated with more severe fetal outcomes, likely facilitating viral transmission to the fetus. Adjunctive treatments aimed at reducing villous and vascular damage may help prevent symptomatic infection and stillbirth in first-trimester CMV cases.