Congenital cytomegalovirus infection: new prospects for prevention and therapy

Abstract

Cytomegalovirus is the commonest congenital viral infection in the developed world, with an overall prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a substantial risk of subsequent neurologic sequelae. These include sensorineural hearing loss, mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy for children with symptomatic congenital cytomegalovirus infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective preconceptual vaccine against CMV could protect against long-term neurologic sequelae and other disabilities.

Fig. 1

A.) Head ultrasound (saggital view) from newborn infant with symptomatic congenital CMV infection. Intracranial and periventricular calcifications are noted (arrows). This infant went on to have severe bilateral SNHL and other developmental disabilities. B.) Brain MRI of infant with congenital CMV infection. Fetal CMV infection was first identified in utero and immune globulin therapy commenced. Saggital (left panel) and axial (right panel) views are demonstrated. 1.5 Tesla, T1-weighted images demonstrate ventriculomegaly, periventricular calcifications, marked loss of brain volume with reduced white matter, pachygyria and lissencephaly on the surface, and very thin cortex. Saggital view demonstrates calcifications most clearly (arrowheads). This infant went on to manifest a seizure disorder and moderate bilateral SNHL.

Fig. 1

A.) Head ultrasound (saggital view) from newborn infant with symptomatic congenital CMV infection. Intracranial and periventricular calcifications are noted (arrows). This infant went on to have severe bilateral SNHL and other developmental disabilities. B.) Brain MRI of infant with congenital CMV infection. Fetal CMV infection was first identified in utero and immune globulin therapy commenced. Saggital (left panel) and axial (right panel) views are demonstrated. 1.5 Tesla, T1-weighted images demonstrate ventriculomegaly, periventricular calcifications, marked loss of brain volume with reduced white matter, pachygyria and lissencephaly on the surface, and very thin cortex. Saggital view demonstrates calcifications most clearly (arrowheads). This infant went on to manifest a seizure disorder and moderate bilateral SNHL.

Fig. 2

Management strategies for congenital CMV infection. Congenital CMV infection may be either asymptomatic or symptomatic at birth. Asymptomatic congenital infection is rarely recognized (since there is seldom any clinical impetus to evaluate an asymptomatic newborn), but may be diagnosed as in incidental finding, or because of concern regarding a primary maternal infection during pregnancy. It is possible that more asymptomatic congenital infections will be recognized in the future because of ongoing programs evaluating the potential value of performing universal CMV screening on all newborns. Such infants require frequent audiological screening, but are not known to benefit from antiviral therapy. Infants with symptomatic congenital CMV infection should be evaluated for CNS involved (by ophthalmological evaluation, CNS imaging studies, audiological evaluation, and when feasible lumbar puncture). If CNS involvement is noted, six weeks of therapy with ganciclovir is known to improve hearing, and possibly neurodevelopmental, outcomes. Oral valganciclovir is an alternative. Infants with symptomatic infection without CNS involvement are not known to benefit from antiviral therapy.