Cytomegalovirus infection during pregnancy: state of the science

Marianne Leruez-Ville, Ina Foulon, Robert Pass, Yves Ville
American Journal of Obstetrics and Gynecology 2020, 223 (3): 330-349
Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. Congenital cytomegalovirus can follow maternal primary infection or nonprimary infection. Sensorineurological 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 3 months around conception but is not informative in women already immune before pregnancy. In Europe and the United States, primary infection in the first trimester are mainly seen in young parous women with a previous child younger than 3 years. Congenital cytomegalovirus should be evoked on prenatal ultrasound when the fetus is small for gestation and 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 magnetic resonance imaging of known infected fetuses show greater than 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 cytomegalovirus infection. Medical therapies such as cytomegalovirus hyperimmune globulins aim to reduce the risk of vertical transmission but 2 randomized controlled trials 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 a randomized controlled trial of 90 pregnant women. In a phase II open-label trial, oral valaciclovir (8 g/d) 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 cytomegalovirus infection is a public health challenge. In view of recent knowledge on diagnosis and pre- and postnatal management, health care providers should reevaluate screening programs in early pregnancy and at birth.

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