Israel Medical Association Journal

Background: The incidence of congenital cytomegalovirus (CMV) infection in Israel is 0.7%. Only 10–15% are symptomatic. Valganciclovir has been shown to improve hearing and neurodevelopmental outcomes in neonates with symptomatic congenital CMV infection. Targeted examination of infants who fail routine neonatal hearing screening or have clinical or laboratory findings suggestive of symptomatic congenital CMV infection may be a cost-effective approach.

Objectives: To assess the possibility of targeted examination for the detection of newborns with symptomatic congenital CMV infection.

Methods: A prospective observational study was conducted in 2014–2015 at two medical centers in northern Israel. Included were all newborns who were tested in the first 3 days of life by polymerase chain reaction (PCR) for urine CMV DNA (n=692), either for failure the hearing screening (n=539, 78%), clinical or laboratory findings suggestive of symptomatic congenital CMV infection, or primary CMV infection during pregnancy (n=153, 22%).

Results: During the study period 15,433 newborns were born. The predicted rate of infection was 10–15% (symptomatic) of 0.7% of newborns, namely 0.07–0.105% or 10–15 infants. In fact, 15 infants (0.11%, 95% confidence interval 0.066–0.175) were diagnosed with symptomatic congenital CMV infection, 2/539 (0.37%) in the failed hearing group and 13/153 (8%) in the clinical/laboratory findings group. The incidence of symptomatic congenital CMV infection was within the predicted range.

Conclusions: Targeted examination of only 4.5% (n=692) of newborns detected the predicted number of infants with symptomatic congenital CMV infection in whom valganciclovir therapy is recommended

Seroconversion to cytomegalovirus occurs in 1%-4% of pregnant women, most of whom are seropositive prior to pregnancy. In 0.2%-2.5% of their newborn infants there is evidence of intrauterine infection; most are born without any clinical findings The typical clinical symptoms of symptomatic congenital CMV[1] are observed in 10-20% of infected neonates. They include intrauterine growth restriction, microcephaly, hepatosplenomegaly, petechiae, jaundice, thrombocytopenia, anemia, chorioretinitis, hearing loss and/or other findings. Long-term neurodevelopmental sequelae include mental retardation, motor impairment, sensorineural hearing loss and/or visual impairment. These may occur even in infants who are free of symptoms at birth. Most infants born with severe neonatal symptoms of congenital CMV are born to mothers with primary infection during pregnancy. However, since about half of the infants infected with CMV in utero, including those with severe neonatal symptoms, are born to mothers with preconceptional immunity, we have to conclude that congenital CMV may be a significant problem even in children born to mothers with pre-pregnancy immunization. This may justify the use of invasive methods for the detection of possible fetal infection even in cases of non-primary CMV infection. This should also be a consideration when deciding upon population screening or immunization for CMV.

Objectives: To define the incidence of congenital CMV infection in two different subpopulations, as a model for the entire population of Israel.

Methods: Urine specimens were randomly collected from 2,000 newborns in Shaare Zedek Medical Center, Jerusalem, and HaEmek Medical Center, Afula (1,000 specimens each). These hospitals have many characteristic differences, presumably representing the diverse population of Israel. Urine specimens were subjected to a CMV PCR[2] reaction and positive specimens were validated by urine viral culture. Maternal seroprevalence was determined in a representative sample of the mothers in each hospital. Epidemiologic characteristics of the mothers were extracted from hospital records and compared.

Results: The population in Shaare Zedek Medical Center was mostly Jewish (95.8%) and urban (87.0%), as compared to that of HaEmek Medical Center (49.2% and 61.0%, respectively, P < 0.01). Nevertheless, CMV seroprevalence was similar: 81.5% and 85%, respectively. Ten (1.0%) and 4 (0.4%) newborns, respectively, were found to have congenital CMV infection (not significant).

Conclusions: The combined incidence of congenital CMV infection in the study population was 0.7% (95% confidence interval 0.3–1.0%). If this rate is extrapolated to the entire population of Israel, then a total of 945 cases of congenital CMV can be expected among the 135,000 annual deliveries. A nationwide screening program for congenital CMV should be considered.

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[1] CMV = cytomegalovirus

[2] PCR = polymerase chain reaction