Early prediction of congenital cytomegalovirus infection and symptoms after maternal primary infection: an in vivo study using cytomegalovirus polymerase chain reaction in chorionic villi and in amniotic fluid.

Abstract

The long interval between the serologic diagnosis of maternal primary infection in the first trimester of pregnancy and the prenatal diagnosis of fetal infection by amniocentesis at 17 weeks of gestation may cause anxiety and distress. Cytomegalovirus polymerase chain reaction in chorionic villi sampled by chorionic villus sampling at 14 weeks of gestation can diagnose trophoblastic infection. This study aimed to assess the diagnosis and prognostic value of cytomegalovirus polymerase chain reaction in chorionic villi in pregnant women with cytomegalovirus maternal primary infection for predicting vertical transmission and related symptoms at birth. This single-center retrospective cohort study enrolled pregnant women referred for cytomegalovirus maternal primary infection in early pregnancy identified by serologic screening before 14 weeks of gestation between October 2019 and December 2024. Secondary prevention with valaciclovir was offered. The primary outcome was vertical transmission, defined by a positive cytomegalovirus polymerase chain reaction in chorionic villi, amniotic fluid obtained by amniocentesis at 17 weeks of gestation, and neonatal saliva/urine at birth (or positive in situ hybridization in terminated pregnancies). The secondary outcomes were symptomatic congenital infection in live-born infants, defined according to the European Congenital Infection Initiative criteria, and sensorineural hearing loss. Overall, 422 women were diagnosed with maternal primary infection, and 330 women had both chorionic villus sampling and amniocentesis. Cytomegalovirus polymerase chain reaction was positive in the trophoblast in 19 of 330 women (5.7%) and associated with maternal-fetal transmission during the course of pregnancy in 89.4% of women, mostly before 17 weeks of gestation (73.7%). No fetal infection occurred in "triple negative cytomegalovirus polymerase chain reaction" in trophoblast, maternal blood, and urine in the first trimester of pregnancy. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of cytomegalovirus polymerase chain reaction in trophoblast to predict congenital infection were 48.28%, 98.34%, 73.68%, and 95.18%. Among the 16 infected newborns who were symptomatic at birth, 2 had bilateral severe-to-profound sensorineural hearing loss (all with positive cytomegalovirus polymerase chain reaction in chorionic villi), and 5 had unilateral sensorineural hearing loss. The specificity and negative predictive values of cytomegalovirus polymerase chain reaction on trophoblasts to predict symptoms at birth were 97.12% and 97.74%, respectively; 96.26% and 99.68% for sensorineural hearing loss at birth, respectively; and 96.55% and 99.35% for long-term symptoms, respectively. Cytomegalovirus polymerase chain reaction on chorionic villi showed high specificity and negative predictive value for fetal infection and related symptoms at birth.