Prevention of congenital cytomegalovirus complications by maternal and neonatal treatments: a systematic review

Abstract

Human cytomegalovirus is the leading non-genetic cause of congenital malformation in developed countries. Congenital CMV may result in fetal and neonatal death or development of serious clinical sequelae. In this review, we identified evidence-based interventions for prevention of congenital CMV at the primary level (prevention of maternal infection), secondary level (risk reduction of fetal infection and disease) and tertiary level (risk reduction of infected neonates being affected by CMV). A systematic review of existing literature revealed 24 eligible studies that met the inclusion criteria. Prevention of maternal infection using hygiene and behavioural interventions reduced maternal seroconversion rates during pregnancy. However, evidence suggested maternal adherence to education on preventative behaviours was a limiting factor. Treatment of maternal CMV infection with hyperimmune globulin (HIG) showed some evidence for efficacy in prevention of fetal infection and fetal/neonatal morbidity with a reasonable safety profile. However, more robust clinical evidence is required before HIG therapy can be routinely recommended. Limited evidence also existed for the safety and efficacy of established CMV antivirals (valaciclovir, ganciclovir and valganciclovir) to treat neonatal consequences of CMV infection, but toxicity and lack of randomised clinical trial data remain major issues. In the absence of a licensed CMV vaccine or robust clinical evidence for anti-CMV therapeutics, patient education and behavioural interventions that emphasise adherence remain the best preventative strategies for congenital CMV. There is a strong need for further data on the use of HIG and other antivirals in pregnancy, as well as the development of less toxic, novel, antiviral agents.

Crystal Structure of the Human Cytomegalovirus pUL50-pUL53 Core Nuclear Egress Complex Provides Insight into a Unique Assembly Scaffold for Virus-Host Protein Interactions

“…Its clinical importance has occasionally been underestimated, as infection of the immunocompetent host may be limited to mild forms of symptoms (1). The main pathogenesis of HCMV is manifested by severe systemic or even life-threatening disease in immunosuppressed hosts and upon congenital infection of neonates (2,3). HCMV pathogenesis is determined by various parameters of immune control, viral productivity, viremia, tissue tropism, and organ damage, as well as manifold regulatory events of virus-host interaction (1).…”

Human Cytomegalovirus Modulates Expression of Noncanonical Wnt Receptor ROR2 To Alter Trophoblast Migration

“…No effective therapy is currently proven to prevent or treat congenital infection. Studies of prevention using vaccines are continuing, and recent studies on efficacy of administration of CMV hyperimmunoglobulin or antiviral drugs to pregnant women with primary CMV infection await confirmation in ongoing randomized studies (17). Understanding the molecular underpinnings of CMV infection of the placenta and the fetus is essential for therapeutic innovations and vaccine design.…”

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

“…uman cytomegalovirus (HCMV), a member of the betaherpesvirus family, is the leading cause of congenital neurological complications in neonates as a result of maternal infection (1)(2)(3)(4). Among immunocompromised patients-especially those with an organ transplant, chemotherapy, or AIDS-the reactivation of virus causes life-threatening diseases, such as gastroenteritis, encephalitis, pneumonitis, and graft rejection (5)(6)(7).…”