Cytomegalovirus shedding and delayed sensorineural hearing loss: results from longitudinal follow-up of children with congenital infection.

BACKGROUND: The pathogenesis of cytomegalovirus (CMV)-related hearing loss is not well understood. OBJECTIVE: To evaluate the relationship between persistent CMV shedding and delayed sensorineural hearing loss in children born with congenital CMV. METHODS: Serial audiologic assessments and CMV cultures of urine and saliva were performed on 580 children who had been diagnosed with congenital CMV infection. RESULTS: Prevalence of CMV culture-positivity in any specimen decreased to approximately 50% by the third birthday and approximately 5% after the seventh birthday. Intermittent shedding occurred in 28% of children. Seventy-seven children had hearing loss at birth and 38 children developed delayed hearing loss by the end of follow-up. In multivariate analyses, delayed hearing loss was strongly associated with symptomatic infection at birth (OR = 5.9, 95% CI: 1.8-18.9) and modestly associated with older age at last culture-positive visit (OR = 1.6, 95% CI: 1.1-2.0, comparing 1-year age differences) Observed rates of delayed hearing loss were 0.79 per 100 person-years for children asymptomatic at birth and 4.29 per 100 person-years for children symptomatic at birth. Between the ages of 6 months and 8 years, we would expect delayed hearing loss to occur in 6.9% of asymptomatic children and in 33.7% of symptomatic children. CONCLUSIONS: The strongest risk factor for delayed hearing loss was CMV-related symptoms at birth, but many asymptomatic children also developed delayed hearing loss. Longer duration of CMV shedding may also be a predictor of delayed hearing loss.

Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome.

BACKGROUND: The relationship between gestational age at time of maternal cytomegalovirus (CMV) infection and outcome of fetal infection is not well defined because the timing of maternal infection is usually not known. OBJECTIVE: To determine whether congenital cytomegalovirus (CMV) infection following primary maternal infection during the first trimester of pregnancy is more likely to lead to central nervous system (CNS) sequelae than fetal infection due to maternal infection later in pregnancy. STUDY DESIGN: Using serum collected during pregnancy from mothers of newborns with congenital CMV infection, maternal infection was categorized as first trimester (<13 weeks) or later based on dates and results of IgG and IgM assays for CMV antibody. Outcome of congenital CMV infection was assessed by longitudinal fotlow-up of the infected cohort. RESULTS: Sensorineural hearing loss was found in 8/34 (24%) of children in the first trimester group, compared with 1/40 (2.5%) in the later infection group (P=0.01, relative risk, 9.6). Considering any CNS sequela (hearing loss, mental retardation, cerebral palsy, seizures, chorioretinitis) 11/34 (32%) first trimester cases were affected compared with 6/40 (15%) in the later infection group (P=0.07, relative risk 2.2). None of the later group had more than one sequela, compared with 4 (12%) of the first trimester group (P=0.04). CONCLUSIONS: Children with congenital CMV infection following first trimester maternal infection are more likely to have CNS sequelae, especially sensorineural hearing loss, than are those whose mothers were infected later in pregnancy. However, some degree of CNS impairment can follow even late gestational infection.

Interval between births and risk of congenital cytomegalovirus infection.

To examine the effect of the interval between maternal cytomegalovirus (CMV) infection and conception on the risk of congenital CMV infection, the congenital CMV infection rate was evaluated relative to the intervals between deliveries in young women. Among mothers who seroconverted between deliveries, the rate of congenital CMV infection among their offspring was highest when the delivery interval was < or =24 months. However, the risk of transmission remained elevated for women with delivery intervals of 25-48 months and for those with delivery intervals >48 months apart.

Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity.

OBJECTIVE: To define hearing outcomes in children with congenital cytomegalovirus (CMV) infection born to mothers with non-primary CMV infection. STUDY DESIGN: A cohort of 300 children with congenital CMV infection identified by newborn virologic screening at the University of Alabama Hospital and a private community hospital in which the type of maternal infection could be classified constituted the study population. Maternal infections were categorized by analyzing serum samples. Children were followed prospectively and underwent serial audiologic evaluations. RESULTS: The frequency of hearing loss was not different between children born to mothers with non-primary infection (10%) and those with primary infection (11%). Significantly more children in the primary infection group had progressive and severe/profound hearing loss compared with children in the non-primary group. The frequency of bilateral, delayed onset, high-frequency, and fluctuating hearing loss was not different between the 2 groups. The mean age of diagnosis of hearing loss was 39 +/- 53 months for children born to mothers with non-primary infection and 13 +/- 21 months for the primary infection group (P = .16). CONCLUSIONS: Maternal preexisting seroimmunity to CMV does not provide complete protection against hearing loss in infants with congenital CMV infection.

Maternal immunity and prevention of congenital cytomegalovirus infection.

CONTEXT: Vaccine development to prevent congenital cytomegalovirus (CMV) infection has been impeded by the uncertainty over whether maternal immunity protects the fetus. OBJECTIVE: To determine whether the presence of maternal antibodies to CMV significantly reduces the risk of congenital CMV infection in future pregnancies. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 3461 multiparous women from a population with a high rate of congenital CMV infection who delivered newborns screened for congenital CMV infection between 1993 and 1998, and whose cord serum specimen from a previous delivery could be retrieved and tested for antibody to CMV. MAIN OUTCOME MEASURE: Congenital CMV infection according to maternal immune status, age, race, parity, and socioeconomic status. RESULTS: Of 604 newborns born to initially seronegative mothers, congenital CMV infection occurred in 18 (3.0%). In contrast, of 2857 newborns born to immune mothers, congenital CMV infection occurred in 29 (1.0%) Two factors, preconception maternal immunity (adjusted risk ratio, 0.31; 95% confidence interval, 0.17-0.58) and maternal age of 25 years or older (adjusted risk ratio, 0.19; 95% confidence interval, 0.07-0.49), were highly protective against congenital CMV infection. No other factors were associated with a reduction in the risk of congenital CMV infection. CONCLUSION: Naturally acquired immunity results in a 69% reduction in the risk of congenital CMV infection in future pregnancies.

Predictors of hearing loss in children with symptomatic congenital cytomegalovirus infection.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is a major cause of sensorineural hearing loss (SNHL) and neurologic impairment in children. Although the majority of children with symptomatic congenital CMV infection develop hearing loss, many symptomatic infants have normal hearing. The purpose of this study was to identify indicators present in the newborn period that have predictive value for the development of hearing loss in children with symptomatic congenital CMV infection. METHODS: Of the 190 children who had symptomatic congenital CMV infection and were born between 1966 and 1997 and enrolled in a follow-up study, hearing outcome was known for 180 children. Follow-up data were analyzed using univariate and multivariate logistic regression analyses to determine the specific demographic, newborn clinical, and laboratory findings predictive of hearing loss. The amount of infectious CMV in urine was quantified in a subset of 21 children who were born between 1994 and 1998. RESULTS: The presence of intrauterine growth retardation, petechiae, hepatosplenomegaly, hepatitis, thrombocytopenia, and intracerebral calcifications was associated with the development of hearing loss on univariate analysis. The presence of microcephaly and other neurologic abnormalities was not predictive of hearing loss. Logistic regression analysis revealed that only petechiae and intrauterine growth retardation independently predicted hearing loss. None of the demographic and other newborn findings predicted progressive hearing loss. The children who developed hearing loss had higher urine CMV titers during infancy than those with normal hearing. CONCLUSION: In children with symptomatic congenital CMV infection, evidence of disseminated infection with or without the presence of neurologic involvement at birth was predictive of the development of hearing loss. However, it was not possible to identify factors that are independently predictive of the development of progressive hearing loss.

Estudio serologico citomegalovirus, virus del herpes simple y de la rubiola, hepatitis B y toxoplasma gondii en dos poblaciones de gestantes en Santiago, Chile / Serological study for cytomegalovirus, herpes simplex virus rubeolla virus, hepatitis B virus and Toxoplasma gondii in 2 populations of pregnant women in Chile

Se llevó a cabo una encuesta serológica de gestantes de estratos socieconómicos mediano (372) y bajo (461) de Santiago, Chile, durante su primera o segunda consulta prenatal, con el fin de determinar la prevalencia de infección por citomegalovirus (CMV), virus de rubéola, herpes simple (HSV) y hepatitis B (HBV), y Toxoplasma gondii en las primeras fases de la gestación. Las muestras se analizaron por ELISA utilizando reactivos comerciales. En la cohorte de bajos ingresos, la tasa de seropositividad fue del 96,5% para CMV, del 97,2% para HSV, del 94,8% para rubéola, del 68,2% para T. gondii y del 1,4% para HBV. En el grupo de medianos ingresos, la tasa de seropositividad fue del 86,8% para CMV, del 87,9% para HVS, del 94,4% para rubéola, del 48,4% para T. gondii y del 1,4% para HBV. Solo las diferencias en la prevalencia de CMV, HSV y T gondii fueron significativas. Los resultados revelan que, en Santiago, las infecciones por CMV, HSV, rubéola y T. gondii se contraen en edad temprana en ambos grupos analizados. A pesar del alto grado de inmunidad resultante, es posible que el riesgo de infecciones congénitas y perinatales por esos agentes sea alto, debido a la constante oportunidad de reactivación y reinfección que se producen con frecuencia en el caso de CMV y HSV. Además, las gestantes susceptibles, aunque son relativamente pocas, están en constante riesgo de contraer esas infecciones tan difundidas en la comunidad. La prevalencia de la hepatitis B, por otra parte, es mucho menor en Chile que en otros países con un grado de desarollo económico similar. Esto parecería indicar que los casos de infección por HBV en neonatos deben ser infrecuentes