Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
The objective of the trial is to investigate whether early treatment with oral valganciclovir
 of infants with both congenital cytomegalovirus infection and sensorineural hearing loss can
 prevent progression of hearing loss.
In the Netherlands all neonates are routinely screened for hearing during the first weeks
 after birth with the Otoacoustic Emissions (OAE) procedure. After the second refer an
 Automated Auditory Brainstem Response (AABR) is performed. The parents of all newborns, born
 at ≥ 37 weeks gestational age, that fail this AABR in the Netherlands (about 550 yearly) will
 be asked for consent for CMV-testing on the dried blood spots. Newborns diagnosed with
 congenital CMV and with confirmed SNHL (≥ 20 dB) are eligible for inclusion. After informed
 consent infants will be offered treatment before the age of 13 weeks (6 weeks valganciclovir
 32 mg/kg daily dose; oral solution). Parents may decide to participate in the trial in the
 control group (no antiviral treatment). Infants will be monitored for leucopenia and liver-
 and kidney function. Inclusion will continue for at least 1.5 years, or until at least 40
 infants have been included in the trial.

 At age 20 months hearing and child development are assessed in the follow-up. Hearing will be
 assessed with Brainstem Evoked Response Audiometry with the Vivosonic Integrity. Child
 development will be assessed with the Bayley Scales of Infant Development III (official Dutch
 translation) and parents will fill in the Dutch Child Development Inventory (NCDI) which will
 give more detailed information on communicative development of their child. The hearing
 assessment and developmental examination will be fulfilled during a home visit. Viral loads
 in blood and urine will be monitored during antiviral treatment as well as twice in the
 control group.

 This study will provide information on the percentage of infants with a congenital CMV
 infection who fail the neonatal hearing screening . The trial will show whether early
 treatment of congenital CMV infected children with hearing impairment prevents deterioration
 of hearing loss and to what extent. The outcome may lead to implementation of congenital CMV
 testing in the neonatal hearing screening program or possibly into the newborn blood
 screening.
Inclusion Criteria Treatment group and refusal control group

 -  Infants with congenital CMV infection, and hearing loss (≥ 20 dB, in one or both
 ears).

 -  Age at time of inclusion is ≤ 12 weeks after birth.

 -  Born at ≥ 37 weeks gestational age.

 -  Birth weight > -2 SD corrected for duration of pregnancy and ethnic origin.

 -  Parental signed informed consent.

 Historical control group

 -  Infants with congenital CMV infection, and hearing loss (≥ 20 dB, in one or both
 ears).

 -  Age at time of inclusion is > 13 weeks after birth.

 -  Born at ≥ 37 weeks gestational age.

 -  Birth weight > -2 SD corrected for duration of pregnancy and ethnic origin.

 -  Parental signed informed consent.

 Exclusion Criteria Treatment group and refusal control group

 -  Previously noted (≤ 12 weeks after birth) symptoms possibly related to congenital CMV,
 for which medical attention was requested. For example: intra uterine growth
 retardation, petechiae, hepatosplenomegaly, jaundice, microcephaly, thrombocytopenia,
 elevated transaminases, elevated bilirubin.

 -  Treatment with other antiviral agents or immunoglobulins.

 -  Solely applicable for treatment group: leucopenia < 0,5 x 10*9/L (blood sample tested
 at t=0).

 Historical control group

 -  Previously encountered (≤ 12 weeks after birth) symptoms possibly related to
 congenital CMV, for which medical attention was requested For example: intra uterine
 growth retardation, petechiae, hepatosplenomegaly, jaundice, microcephaly,
 thrombocytopenia, elevated transaminases, elevated bilirubin.

 -  Treatment with (val)ganciclovir.

 -  Treatment with other antiviral agents or immunoglobulins.