Abstract
OBJECTIVE: To estimate the residual risk of maternal-fetal transmission after primary cytomegalovirus (CMV) infection in the periconceptional period or the first trimester in women treated with valacyclovir, and to assess whether the presence of glycoprotein B2 (gB2)-specific immunoglobulin (Ig)-G antibodies on immunoblot analysis refines fetal risk prediction. METHODS: This was a retrospective single-center study conducted at University Hospital Tübingen, Tübingen, Germany, between October 2023 and June 2025. Pregnant women with a primary CMV infection diagnosed < 14 weeks' gestation who received valacyclovir (8 g/day) were included in the study. The diagnosis of a recent primary CMV infection was based on maternal serology results, specifically positive anti-CMV-immunoglobulin (Ig)-G and -IgM levels, and low or intermediate IgG avidity. Additionally, prior to initiation of valacyclovir treatment, the presence or absence of glycoprotein B (gB)2-specific IgG antibodies was determined using a commercial line immunoblot. The primary outcome was maternal-fetal transmission of CMV detected at the time of second-trimester amniocentesis. RESULTS: Eighty-five women met the inclusion criteria, including 47 with periconceptional and 38 with first-trimester maternal CMV infection. Median maternal and gestational age at the time of diagnosis of primary maternal CMV infection were 33.1 (interquartile range (IQR), 29.9-34.9) years and 7.4 (IQR, 6.4-8.9) weeks, respectively. Amniocentesis was performed at a median gestational age of 20.6 (IQR, 20.1-21.0) weeks. Overall, maternal-fetal transmission was detected in 7/85 (8.2%) cases at the time of amniocentesis. All CMV transmissions occurred in women without gB2-specific IgG antibodies (7/55 (12.7%)), while no transmissions occurred in those with gB2-specific IgG antibodies (0/30 (0%)) (P = 0.048). CONCLUSIONS: In women with a primary CMV infection treated with valacyclovir, the presence of gB2-specific IgG antibodies on immunoblot analysis identifies a subgroup with a low residual risk of maternal-fetal transmission. Incorporating gB2-specific IgG antibodies status into risk stratification may improve patient counseling and clinical decision-making. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.