Follow-Up of Infants With Congenital Cytomegalovirus Following Maternal Primary Infection in the First Trimester and Normal Fetal Brain Imaging at Midgestation.

Objective: To determine outcomes at birth and postnatal sequelae of congenital cytomegalovirus (cCMV) infection following maternal primary infection in the first trimester with normal fetal brain imaging at midgestation.

Methods: A retrospective, single-center cohort study was conducted, including all cases of proven cCMV infection following maternal primary infection in the first trimester from 2014 until 2021 and normal fetal brain imaging before 22 weeks of gestation. All pregnancies were followed according to our protocol, which offers amniocentesis at least 8 weeks after the onset of infection, serial ultrasound scans, and a fetal MRI in the third trimester. No women received treatment with CMV hyperimmune globulin or Valacyclovir during pregnancy. Follow-up of newborns was obtained, and newborns were classified as symptomatic or asymptomatic at birth. Postnatal sequelae were evaluated, and cases with a follow-up period of less than 12 months were excluded.

Results: We found 42 newborns with cCMV, confirmed at birth by PCR for the CMV genome in neonatal urine samples, and normal fetal brain imaging up to 22 weeks of gestation. Extracerebral signs of infection were present in 3/42 fetuses at the second trimester ultrasound (20-22 weeks of gestation). In the third trimester (28-32 weeks of gestation), none showed abnormal brain sonographic findings, but four exhibited extracerebral signs of CMV infection. Among 42 newborns, 29 were classified as asymptomatic (29/42, 69.1%) and 13 as symptomatic at birth (13/42, 30.9%, 95%CI 17.6%-47.1%). Eight newborns had abnormal cranial ultrasound/MRI (8/42, 19%), one presented abnormal postnatal brain imaging associated with hearing loss and four had sensorineural hearing loss (SNHL) at initial assessment. All were treated with oral Valganciclovir. Four newborns with normal hearing at birth had delayed onset SNHL. One case of hearing loss improved after treatment and returned to normal hearing. At a median follow-up of 35 months, 8 infants had hearing loss (8/42, 19%, 95%CI 8.6%-34.1%) and none presented with severe brain abnormalities.

Conclusion: For infants with congenital CMV following untreated first trimester maternal primary infection, the absence of abnormal prenatal brain ultrasound findings at the mid-trimester morphology scan does not rule out the possibility of postnatal neuroimaging anomalies or the need for treatment after birth. However, no severe brain abnormalities were detected after birth in our cohort, and the only observed sequelae were sensorineural hearing loss.