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

Background: Cytomegalovirus (CMV) infection during pregnancy is the most common cause of intrauterine infection, and is a common cause of sensorineural hearing loss and mental retardation. 

Objectives: To evaluate trends in amniocentesis and pregnancy outcome in women with suspected cytomegalovirus (CMV) infection during the first trimester.

Methods: All blood tests for CMV immunoglobulin M (IgM) done between 2008 and 2009 on pregnant women who were enrolled in the Maccabi Healthcare Services were retrieved from laboratory database. Immunoglobulin G (IgG) avidity was measured and women were classified according to the risk of acquiring CMV infection. For each patient, performance of amniocentesis and whether pregnancy came to term were recorded.

Results: Of 109,439 pregnant women evaluated during the study period, 76,712 (70.1%) were tested for CMV IgM, and 792 (1.03%) were found to be positive. Among women with positive IgM, only 205 (25.9%) underwent amniocentesis. When compared with women with negative CMV IgM, the rate of pregnancy cessation was doubled in women with positive CMV IgM (28.3% vs. 14.3%, P < 0.05) and mostly elevated in women with a high risk of acquiring CMV (42.3% pregnancy cessation). Among women with positive CMV IgM, those who did not undergo amniocentesis were more likely to abort than those who performed amniocentesis (35.6% vs. 7.3%, P < 0.05). 

Conclusions: More women with suspected CMV infection during the first trimester of pregnancy aborted before all means of detection were utilized to rule out or confirm fetal infection with CMV.

 

Objectives: To retrospectively analyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood.

Methods: CMV DNA was detected by rt-PCR performed on infants’ cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation.

Results: During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen (82%) infants would not otherwise have been diagnosed.

Conclusions: The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

Background: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested.

Objectives: To examine whether their prevalence differs in two latitudinally different populations.

Methods: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia.

Results: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV[1] were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001).

Conclusions: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.

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