We read carefully the article of Leruez-Ville et al about the efficacy evaluation of oral valacyclovir for pregnant women carrying a symptomatic cytomegalovirus-infected fetus, who are at high risk for developing both neurosensory and neurological impairments. Symptomatic fetuses, defined by the presence of measurable extracerebral or mild cerebral ultrasound signs, were treated in utero from the prenatal diagnosis, performed at a median age of 25.9 weeks’ gestation, to the delivery or the termination of pregnancy. As noted by the authors, high-dosage valacyclovir was effective in improving the outcome of the infected fetuses. At the interim analysis, 8 of 11 women delivered asymptomatic neonates that were still asymptomatic at 12 months old.

Over the last decades, the natural history of the cytomegalovirus (CMV) infection in pregnancy has been slightly changed, being the object of several therapeutic attempts. Vaccination is not available and no prenatal treatment of congenital CMV has yet been validated. The use of CMV-specific hyperimmune globulin to prevent vertical transmission has obtained contrasting results. As suggested, around 10% of infected neonates are symptomatic at birth and their risk of sequelae reaches 58%. On the other hand, the risk of sequelae in asymptomatic newborns is around 13%.

We understood that the difference in viral load of both symptomatic and asymptomatic newborns may be critical, particularly if the predictive value for developing symptoms at birth in an infected fetus is assessed only by interpreting the results of both prenatal imaging and laboratory tests. Increasing the number of data from human studies indicates that human cytomegalovirus infection interferes with the differentiation of trophoblast progenitor cells in the human placenta so that the passive immunization with hyperimmune globulin has been shown to reduce viral replication, to enable the compensatory growth of chorionic villi, to increase the perfused placental surface, and, for some babies, to improve the outcome.

Although this study is not a randomized controlled trial, this is the first one that reports the efficacy of an antiviral drug in cytomegalovirus-infected fetuses. As a consequence, this study should encourage new trials using valacyclovir as a first-line safe and effective treatment in CMV-affected pregnant women and comparing this last one with the new emerging and more potent anticytomegalovirus drugs. However, based on our evaluation of the study by Leruez-Ville et al, it seems that together with prenatal imaging and laboratory tests, the infection natural history in symptomatic and asymptomatic neonates could be better predicted if associated with placenta pathology examination. Once again we thank the authors for bringing these considerations to the forefront.