OBJECTIVE. Two recognized sources of maternal cytomegalovirus infection are young children and sexual activity. Previous studies evaluated either maternal exposures to young children or sexual activity, but these studies did not evaluate whether both of these maternal cytomegalovirus sources contribute to increases in congenital cytomegalovirus infections within populations with a high prevalence of infection among women of childbearing age. Our objective with this study was to investigate whether maternal cytomegalovirus exposure through young children and by sexual activity increases the risk for congenital cytomegalovirus infection in their offspring. METHODS. A case-control study of 519 women from a delivery population in Birmingham, AL, between December 1992 and July 1998 was undertaken to measure the association between maternal cytomegalovirus exposures and an increased risk for congenital cytomegalovirus infection in their infants. Routine newborn cytomegalovirus screening at the hospital identified infants with congenital cytomegalovirus infection. The cases (n = 150) were women who delivered an infant with congenital cytomegalovirus infection, and the control subjects (n = 369) were randomly selected from the delivery population of women whose newborns were uninfected. Investigation of exposures included using a standardized maternal interview, prenatal and medical chart abstraction, and laboratory confirmation of cytomegalovirus infection. RESULTS. Significant associations between congenital cytomegalovirus infection and caring for preschool children in the year before delivery, onset of sexual activity <2 years before delivery, sexually transmitted diseases during pregnancy, household size >3 people, and maternal age <25 years were identified. Women who cared for preschool children in the year before delivery and also became sexually active within the 2 years before delivery were at greatest risk for delivering an infant with congenital cytomegalovirus infection. CONCLUSIONS. Caring for young children and recent onset of sexual activity contribute to an increased risk for congenital cytomegalovirus infection in the offspring of young women. Copyright © 2006 by the American Academy of Pediatrics.