Intrauterine therapy of cytomegalovirus infection with valganciclovir: review of the literature

Abstract

Congenital cytomegalovirus (CMV) infection is the leading cause for sensorineural hearing loss and mental retardation in children without genetic diseases worldwide. There is little evidence guiding therapeutic strategies during pregnancy when intrauterine fetal CMV infection is confirmed. We provide a systematic review of the use of ganciclovir (GCV) or VGCV during pregnancy discussing safety of its use for mother and fetus and describe two cases of intrauterine therapy of fetal CMV infection with valganciclovir (VGCV). A PubMed database search was done up to November 16, 2016 without any restrictions of publication date or journal, using the following keywords: "valganciclovir" or "ganciclovir" and "pregnan*". Furthermore, citations were searched and expert references were obtained. Reported cases were considered if therapy was in humans and initiation of treatment of the CMV infection was during pregnancy. In total, seven case reports were retrieved which described GCV or VGCV use during pregnancy for fetal or maternal CMV infection. In the four cases of treatment for maternal CMV infection, no negative effects on the fetus were reported. Three cases of GCV administration to pregnant woman with the intention of fetal treatment after proven fetal infection were found. We additionally present two cases of VGCV treatment in pregnancy from our center of tertiary care. VGCV seems to be a safe treatment for congenital CMV infection for the mother and the fetus. Therapeutic concentrations can be achieved in the fetus by oral intake of the mother and CMV replication can be suppressed. Larger studies are needed to evaluate this therapeutic intervention and the long-term effects.

Impact of the Israeli Ministry of Health Cytomegalovirus Guidelines on the Local Pregnancy Outcome

“…It was also demonstrated in this work that ganciclovir crosses the placenta and has an affect at the CSF level to reduce the viral load during brain development [11]. There are no known serious side effects of antiviral treatment to the mother, and oral treatment is sufficient to reach therapeutic levels in the fetus [12]. Although there are works presenting the benefit of universal newborn screening for congenital CMV infection, this early diagnosis and early intervention with medical and other therapies can reduce the CMV sequelae of the infected newborns [5].…”

Is it time for routine prenatal serological screening for congenital cytomegalovirus?

“…[52][53][54][55] One publication reported in utero treatment of two infected fetuses. 31 Their two mothers were treated for 6 to 8 weeks with T A B L E 2 Hyper-immune globulins and valaciclovir to prevent fetal transmission after maternal primary infection…”

“…Ganciclovir, and its prodrug valganciclovir, are the main antiviral drug successfully used in immunosuppressed patients with CMV disease but they are not recommended in pregnancy. Ganciclovir crosses the placenta barrier with a ratio of 1.14 to 1.21 in term‐placenta 29‐31 . This drug has shown high genotoxicity in vitro contrasting with no carcinogenicity reported in animal models and in humans 32 .…”

“…Ganciclovir crosses the placenta barrier with a ratio of 1.14 to 1.21 in term-placenta. [29][30][31] This drug has shown high genotoxicity in vitro contrasting with no carcinogenicity reported in animal models and in humans. 32 Teratogenicity has been reported in rats treated in utero, with irreversible testicular abnormalities, although this was seen only with high dosage giving peak concentrations 4 to 5 times higher than the ones observed in humans.…”

Fetal and maternal outcome after hyperimmunoglobulin administration for prevention of maternal–fetal transmission of cytomegalovirus during pregnancy: retrospective cohort analysis

“…In a non-randomized and non-controlled study, high-dose Valacyclovir was used for women with primary CMV infection during pregnancy which resulted in a better outcome for newborns with cCMV [17]. For in utero treatment with Valganciclovir, there are only case reports available [18].…”