Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial.
OBJECTIVE
To evaluate the efficacy and safety of ganciclovir therapy in neonates with congenital cytomegalovirus (CMV) disease.


METHODS
Neonates with symptomatic CMV disease involving the central nervous system were randomly assigned to receive 6 weeks of intravenous ganciclovir versus no treatment. The primary end point was improved brainstem-evoked response (BSER) between baseline and 6-month follow-up (or, for patients with normal baseline hearing, normal BSER at both time points).


RESULTS
From 1991 to 1999, 100 patients were enrolled. Of these, 42 patients had both a baseline and 6-month follow-up BSER audiometric examination and thus were evaluable for the primary end point. Twenty-one (84%) of 25 ganciclovir recipients had improved hearing or maintained normal hearing between baseline and 6 months versus 10 (59%) of 17 control patients (P=.06). None (0%) of 25 ganciclovir recipients had worsening in hearing between baseline and 6 months versus 7 (41%) of 17 control patients (P<.01). A total of 43 patients had a BSER at both baseline and at 1 year or beyond. Five (21%) of 24 ganciclovir recipients had worsening of hearing between baseline and > or =1 year versus 13 (68%) of 19 control patients (P<.01). A total of 89 patients had absolute neutrophil counts determined during the course of the study; 29 (63%) of 46 ganciclovir-treated patients had grade 3 or 4 neutropenia during treatment versus 9 (21%) of 43 control patients (P<.01).


CONCLUSIONS
Ganciclovir therapy begun in the neonatal period in symptomatically infected infants with CMV infection involving the central nervous system prevents hearing deterioration at 6 months and may prevent hearing deterioration at > or =1 year. Almost two thirds of treated infants have significant neutropenia during therapy.
Kimberlin
David W
DW
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA. dkimberlin@peds.uab.edu
Lin
Chin-Yu
CY
Sánchez
Pablo J
PJ
Demmler
Gail J
GJ
Dankner
Wayne
W
Shelton
Mark
M
Jacobs
Richard F
RF
Vaudry
Wendy
W
Pass
Robert F
RF
Kiell
Jan M
JM
Soong
Seng-jaw
SJ
Whitley
Richard J
RJ
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D002114:Calcinosis / Q000453:epidemiology / Q000473:pathology; D020805:Central Nervous System Viral Diseases / Q000151:congenital* / Q000188:drug therapy* / Q000453:epidemiology; D003404:Creatinine / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000009:adverse effects / Q000627:therapeutic use*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D006529:Hepatomegaly / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D012720:Severity of Illness Index; D013163:Splenomegaly / Q000139:chemically induced / Q000453:epidemiology; D013997:Time Factors
D000998:Antiviral Agents; D003404:Creatinine; D015774:Ganciclovir