Prevention of Primary Cytomegalovirus Infection in Pregnancy

Abstract

Background: Cytomegalovirus (CMV) is the leading infectious agent causing congenital sensorineural hearing loss and psychomotor retardation. CMV vaccine is currently unavailable and treatment options in pregnancy are limited. Susceptible pregnant women caring for children are at high risk for primary infection. CMV educational and hygienic measures have the potential to prevent primary maternal infection.

Methods: A mixed interventional and observational controlled study was conducted to investigate the effectiveness of hygiene information among pregnant women at risk for primary CMV infection for personal/occupational reasons. In the intervention arm, CMV-seronegative women, identified at the time of maternal serum screening for fetal aneuploidy at 11-12 weeks of gestation, were given hygiene information and prospectively tested for CMV until delivery. The comparison arm consisted of women enrolled at delivery who were neither tested for nor informed about CMV during pregnancy, and who had a serum sample stored at the screening for fetal aneuploidy. By design, groups were homogeneous for age, parity, education, and exposure to at least one risk factor. The primary outcome was CMV seroconversion. Acceptance of hygiene recommendations was a secondary objective and was measured by a self-report.

Findings: Four out of 331 (1.2%) women seroconverted in the intervention group compared to 24/315 (7.6%) in the comparison group (delta = 6.4%; 95% CI 3.2-9.6; P < 0.001). There were 3 newborns with congenital infection in the intervention group and 8 in the comparison group (1 with cerebral ultrasound abnormalities at birth). Ninety-three percent of women felt hygiene recommendations were worth suggesting to all pregnant women at risk for infection.

Interpretation: This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for CMV vaccine to become available, the intervention described may represent a responsible and acceptable primary prevention strategy to reduce congenital CMV.

Keywords: Cytomegalovirus; Hygiene measures; Pregnancy; Prevention; Primary infection.

Fig. 1

Overview of the study design. Participation in the study was restricted to adult (> 18 years of age) Italian pregnant women undergoing serum screening for fetal aneuploidy at 11–12 weeks of gestation and at risk for CMV infection. Interpretation of IgM-positive results and prenatal or neonatal diagnosis of congenital CMV infection in case of maternal seroconversion or primary infection in the first trimester of gestation were performed outside of the present study as part of routine care in case of suspected or confirmed primary CMV infection (dotted boxes).

Fig. 2

Enrollment and outcome. Interventio group. Twenty-one women found to be CMV IgM-positive at enrollment were further tested for IgG avidity (dotted box). Avidity index was high (> 45%), thus excluding a primary CMV infection, in the previous 3 months in 15 women. One woman had avidity in the intermediate range (25%–45%), indicating a possible primary infection in the past 6 months, and 5 women had low (< 25%) avidity indexes compatible with a recent (< 3 months) primary infection. Two women diagnosed with primary infection in the first trimester of gestation opted for prenatal diagnosis of congenital CMV infection and amniocentesis was performed at 20 weeks of gestation.

Fig. 3

Enrollment and outcome. Comparison group. In the comparison group, 56 women were excluded because they were CMV-seronegative at the beginning of pregnancy, they received hygiene information and were monitored for CMV during pregnancy. Fourteen women who tested IgM-positive on stored serum samples at 11–12 weeks of gestation were also tested for avidity of CMV-specific IgG (dotted box). A low avidity index indicating a primary infection acquired in the first trimester of gestation was found in 4 of them. Of the 24 women who seroconverted during pregnancy, 4 were IgM-negative when tested at delivery. All the 291 CMV-seronegative women at delivery received CMV counseling.