Secondary prevention of congenital cytomegalovirus infection with valacyclovir following maternal primary infection in early pregnancy.

Abstract

Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim was to evaluate, in a single center offering CMV serology screening at 11-14 gestational weeks, secondary prevention of cCMV by administration of high-dosage maternal oral valacyclovir (VACV) in the first trimester of pregnancy. This was a case-control study in a longitudinal cohort of pregnancies with CMV-MPI diagnosed prior to 14 weeks of gestation by serology screening (immunoglobulin (Ig) M and IgG measurement and IgG avidity) between 2009 and 2020. From October 2019 onwards, all women presenting at our center with MPI before 14 weeks' gestation were offered treatment with high-dosage oral VACV (8 g/day, 4 g twice/day). We used propensity score matching to compare fetal infection rates in cases treated with maternal oral VACV (8 g/day) with those in untreated controls. Fetal infection was assessed following amniocentesis at 17-22 weeks of gestation, by polymerase chain reaction (PCR) analysis of amniotic fluid for viral DNA. Of 310 cases of CMV-MPI identified, 269 underwent amniocentesis for PCR. Of these, 66 were offered, and 65 accepted, treatment with VACV. From the remaining untreated cases, we selected 65 controls, matched for proportion of periconceptional infections and gestational age at amniocentesis. VACV was initiated at a median gestational age of 12.71 (interquartile range (IQR), 10.00-13.86) weeks and the median duration of treatment was 35 (IQR, 26-54) days. On multivariate logistic regression, fetal infection was lower in the treated group (odds ratio, 0.318 (95% CI, 0.120-0.841); P = 0.021). One treated patient developed acute renal failure 4 weeks after initiation of VACV therapy, but this resolved within 5 days after treatment was stopped. This study confirms the acceptability, tolerance and benefit of secondary prevention by VACV of cCMV infection in a clinical setting with a well-established routine maternal serum screening policy in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.