Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system☆☆☆
Presented at the 2006 Pediatric Academic Societies/Society for Pediatric Research Annual Meeting, San Francisco, CA, April 29, 2006; Abstract # 752908
Received 1 April 2009; received in revised form 3 August 2009; accepted 13 August 2009. published online 22 September 2009.
Abstract
Background
Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS).
Objectives
To assess the neurodevelopmental impact of ganciclovir therapy in this population.
Study design
100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment. Denver developmental tests were performed at 6 weeks, 6 months, and 12 months. For each age, developmental milestones that ≥90% of normal children would be expected to have achieved were identified. The numbers of milestones not met (“delays”) were determined for each subject. The average number of delays per subject was compared for each treatment group.
Results
At 6 months, the average number of delays was 4.46 and 7.51, respectively, for ganciclovir recipients and “no treatment” subjects (p=0.02). At 12 months, the average number of delays was 10.06 and 17.14, respectively (p=0.007). In a multivariate regression model, the effect of ganciclovir therapy remained statistically significant at 12 months (p=0.007).
Conclusions
Infants with symptomatic congenital CMV involving the CNS receiving intravenous ganciclovir therapy have fewer developmental delays at 6 and 12 months compared with untreated infants. Based on these data as well as the previously published data regarding ganciclovir treatment and hearing outcomes, 6 weeks of intravenous ganciclovir therapy can be considered in the management of babies with symptomatic congenital CMV disease involving the CNS. If treatment is initiated, it should be started within the first month of life and patients should be monitored closely for toxicity, especially neutropenia. Since existing data only address the treatment of symptomatic congenital CMV disease involving the CNS, these data cannot be extrapolated to neonates with other manifestations of CMV disease, including asymptomatic babies and symptomatic babies who do not have CNS involvement.
aDepartment of Pediatrics, University of Alabama at Birmingham, United States
bDepartment of Medicine, University of Alabama at Birmingham, United States
cDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States
dDepartment of Pediatrics, Baylor College of Medicine, Houston, TX, United States
eDepartment of Pediatrics, University of California at San Diego, United States
fCook Children's Medical Center, Fort Worth, TX, United States
gDepartment of Pediatrics, University of Arkansas, Little Rock, United States
hDepartment of Pediatrics, University of Alberta, Edmonton, Canada
Corresponding author at: Division of Pediatric Infectious Diseases, The University of Alabama at Birmingham, 1600 Seventh Avenue South, CHB 303, Birmingham, AL 35233, United States. Tel.: +1 205 934-5316; fax: +1 205 975 9972.
☆ This work was supported under contract with the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID) (N01-AI-30025, N01-AI-65306, N01-AI-15113, N01-AI-62554), and by grants from the General Clinical Research Center Program (M01-RR00032) and the State of Alabama.
ABSTRACT