Cytomegalovirus in Pregnancy: Effects on the Developing Embryo and Fetus, Diagnosis and Treatment: Where to Go Now? A Narrative Review

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformations, often presenting with atypical clinical findings. Fetal damage is most severe following primary maternal infection during the first trimester of pregnancy, with the likelihood of transmission increasing with pregnancy advancement. CMV damage may continue to intensify during the early postnatal years. In this narrative review we summarized publications from the last 30 years addressing the epidemiology, diagnosis, prevention and treatment of CMV in pregnancy, with a special emphasis on embryonic and fetal damage. Substantial progress has been made in the diagnosis and treatment of CMV infection during pregnancy, warranting a reconsideration of current clinical approaches. Assessment of viral load enables prediction of fetal infection; its reduction by maternal treatment with valacyclovir may lower both the rate and severity of transmission. Confirmed fetal infection can be diagnosed by amniocentesis and viral DNA detection. Clinical manifestations in infants may be evident at birth (cCMV) or gradually emerge during the first years. The most common fetal damage is hearing loss alongside a variety of brain lesions resulting in significant neurological deficits, including intellectual impairment. Brain involvement is diagnosed by ultrasound or magnetic resonance imaging (MRI). Pharmacological treatment with ganciclovir or valganciclovir, if initiated early after birth, can slow the progression of hearing loss and may ameliorate other neurological and neurodevelopmental deficits. As of today, there is no approved CMV vaccine for prevention. The mRNA-1647's vaccine, currently in phase 3 clinical trial, appears promising. These advances underscore the need for screening pregnant women in the first trimester and newborn infants of mothers suspected of having CMV infection. Neurodevelopmental follow up for several years, including hearing and visual assessment, is advised in all infants positive for CMV. Infants with clinical manifestations should be offered treatment as early as possible following diagnosis of cCMV.