The principle objectives will be to assess the efficacy of antiviral therapy commenced in the first three months of life, compared to placebo or no treatment in infants with symptomatic congenital CMV infection. Efficacy will be evaluated in terms of a reduction in mortality in the first year of life, and the prevention or reduction of cognitive, developmental, motor, visual or audiological sequelae upon completion of therapy and at follow up at one year of age and in later childhood where data are available. Our secondary objectives will be to determine the effects of antiviral therapy on the incidence of complications of antiviral therapy in this age group (nephrotoxicity and bone marrow suppression, i.e. neutropenia, thrombocytopenia, anemia) and of adverse events during the intervention, and to evaluate effects on non-neurological sequelae of congenital CMV infection (elevated liver transaminases) and of active viral shedding in the urine and blood at follow up at one year of age and in later childhood where applicable.
Firstly, the review will compare a given antiviral agent (e.g. intravenous ganciclovir) versus placebo or no treatment.
Secondly, the review will compare two or more different antiviral agents.
Thirdly, it will compare different durations of treatment with a given antiviral agent (e.g. intravenous ganciclovir) using the one dosing regimen.
Fourthly, it will compare different dosing regimens of a given antiviral agent (e.g. intravenous ganciclovir) given for the same duration.
Prespecified subgroup analysis will include:
The presence or absence of any central nervous system involvement at study enrolment (i.e. with or without one or more signs of central nervous system abnormality at enrolment on clinical examination or cranial imaging such as microcephaly, chorioretinitis, seizures, intracranial calcifications, sensorineural hearing loss, abnormality on CT scan).
The presence or absence of abnormal findings on cranial CT imaging at study enrolment.
The presence or absence of microcephaly (head circumference less than third percentile) at study enrolment.
The presence or absence of chorioretinitis at study enrolment.
Gestational age: preterm (<37 weeks gestation) or term.
The age at which the intervention was commenced (i.e. within the neonatal period, or from one to three months of age).
This is a protocol.