P RN CMV IN NEONATE X VALGANCICLOVIR

Cytomegalovirus infection during pregnancy: State of the science

Marianne Leruez-Ville, Ina Foulon, Robert Pass, Yves Ville

American Journal of Obstetrics and Gynecology 2020 February 24

Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main non-genetic cause of congenital sensorineural hearing loss and neurological damage. Congenital CMV can follow maternal primary infection or non-primary infection. Sensori-neurological morbidity is confined to the first trimester with up to 40-50% of infected neonates developing sequelae after first trimester primary infection. Serological testing before 14 weeks is critical to identify primary infection within three months around conception but is not informative in women already immune before pregnancy. In Europe and the US, primary infection in the first trimester are mainly seen in young parous women with a previous child below 3. Congenital CMV should be evoked on prenatal ultrasound when the fetus is small for gestation, shows echogenic bowel, effusions, or any cerebral anomaly. Although the sensitivity of routine ultrasound in predicting neonatal symptoms is around 25%, serial targeted ultrasound and MRI of known infected fetuses show over 95% sensitivity for brain anomalies. Fetal diagnosis is done by amniocentesis from 17 weeks. Prevention consists of both parents avoiding contact with body fluids from infected individuals, especially toddlers, from before conception until 14 weeks. Candidate vaccines failed to provide more than 75% protection for >2 years in preventing CMV infection. Medical therapies such as CMV hyperimmune globulins aim to reduce the risk of vertical transmission but 2 RCTs have not found any benefit. Valaciclovir given from the diagnosis of primary infection up to amniocentesis decreased vertical transmission rates from 29.8% to 11.1% in the treatment group in an RCT of 90 pregnant women. In a phase II open label trial, oral valaciclovir (8g/day) given to pregnant women with a mildly symptomatic fetus was associated with a higher chance of delivering an asymptomatic neonate (82%), compared with an untreated historical cohort (43%). Valganciclovir given to symptomatic neonates is likely to improve hearing and neurological symptoms, the extent of which and the duration of treatment are still debated. In conclusion, congenital CMV infection is a public health challenge. In view of recent knowledge on diagnosis, pre- and postnatal management, health care providers should re-evaluate screening programs in early pregnancy and at birth.