The objective of this project is to define the outcome of congenital CMV infection. Emphasis is placed on determining the role of type of maternal infection (primary versus recurrent) and gestational age as risk factors for sequelae, and evaluating the role of matrnal and infant immune responses as determinants of clinical outcome. Major milestones that have resulted from research that utilized GCRC follow-up of patients include: 1) The transplacental transmission rate of CMV after primary maternal infection is 35-40%.; 2) Preconceptional maternal immunity provides substantial (but not complete) protection from fetal damage; 3) Congenital CMV infection is the leading cause of deafness in children; 4) About 75% of hearing loss in congenital CMV infection progresses postnatally; 5) The rate of congenital CMV infection is markedly increased among offspring of adolescent mothers; 6) The majority of human CMV neutralizing antibodies are directed toward the envelope glycoprotein B; 7) Maternal sexual activity as indicated by STD's and young age at onset of sexual activity is associated with increased risk of congenital CMV infection; 8) 80-90% of infants with congenital CMV infection who are symptomatic at birth will have CNS sequelae; 9) First trimester maternal infection carries greater risk of sequelae in the infected fetus than infection later in pregnancy; 10) Asymptomatic congenital CMV infection is likely a leading cause of deafness in young children; 11) A cranial CT scan is a good predictor of an adverse neurodevelopmental outcome in neonates with symptomatic congenital CMV infection. Current major objectives are focused on determining whether maternal infection within one to two years prior to conception increases the risk of congenital CMV Infection in offspring, whether children with congenital CMV infection who appear normal at birth have increased risk for mental retardation, whether infant immune response to CMV, qualitatively and quantitatively defined, predicts outcome, and whether the amount of CMV virus burden in children with congenital CMV infection correlates with outcome.
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