Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy

Abstract

Background: In 0.5-4% of pregnancies, the prospective mother sustains a primary infection with human cytomegalovirus (HCMV). An HCMV infection of the fetus in the first or second trimester can cause complex post-encephalitic impairment of the infant brain, leading to motor and mental retardation, cerebral palsy, epilepsy, retinal defects, and progressive hearing loss.

Methods: This review is based on pertinent publications from January 2000 to October 2016 that were retrieved by a selective search in PubMed employing the terms "cytomegalovirus and pregnancy" and "congenital cytomegalovirus."

Results: 85-90% of all neonates with HCMV infection are asymptomatic at birth. The main long-term sequela is hearing impairment, which develops in 8-15% of these affected children. Hygienic measures can lower the risk of primary HCMV infection in pregnancy by 50-85%. The first randomized and controlled trial (RCT) of passive immunization with an HCMV-specific hyper - immune globulin (HIG) preparation revealed a trend toward a lower risk of congenital transmission of the virus (30% versus 44% with placebo, p = 0.13). The effect of HIG was more marked in the initial non-randomized trial (15% versus 40%, p = 0.02). The RCT also showed HIG to be associated with a higher frequency of fetal growth retardation and premature birth (13% versus 2%, p = 0.06). Valaciclovir is a further, non-approved treatment option.

Conclusion: In the absence of an active vaccine against HCMV, counseling about hygienic measures may currently be the single most effective way to prevent congenital HCMV infection. Moreover, HCMV serologic testing is recommended in the guideline of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Further randomized trials of treatment with HIG and with valaciclovir are urgently needed so that the options for the prevention and treatment of congenital HCMV infection can be assessed.

FIGURE 1

Study-based projections on the epidemiology of congenital infection with the human cytomegalovirus (HCMV) in populations with high and low seroprevalence in absolute numbers (, , , – e5, e8, e10, e11). The term “permanent disabilities“ includes symptoms that can only be detected with special devices, e.g. subclinical hearing deficit and cognitive late sequelae * Rate of disabilities at age 2 years (e5)

Figure: Petechiae in a newborn with congenital human cytomegalovirus infection requiring intensive care.

Figure 2

Laboratory diagnostic procedure (from [e11]: Courtesy of the German Association for the Control of Virus Diseases (Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten) and the German Society for Virology) (Deutsche Gesellschaft für Virologie) to determine the human cytomegalovirus (HCMV) infection status in pregnant women with suspected primary HCMV infection, combined with possible actions. Blue font: Result constellation; red font: interpretation; green border: actions; red border: further investigations required; gray background: constellation of results typical for primary HCMV infection. * Note: The HCMV serostatus is determined at the start of pregnancy (HCMV screening), solely based on HCMV immunoglobulin (Ig)G testing. For more detailed information refer to the S2K guideline of the Association of the Scientific Medical Societies in Germany (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften) on the laboratory testing recommended to assess viral infections relevant in pregnancy (e11). DNA, deoxyribonucleic acid; false-pos, false positive; neg, negative; PCR, polymerase chain reaction; pos, positive; WG, weeks’ gestation

eFigure 1

Prenatal ultrasound image of a fetus at 26 weeks’ gestation after asymptomatic maternal human cytomegalovirus (HCMV) primary infection during the first trimester. The fetal CNS is damaged by embryofetal HCMV encephalitis: mild extension of the intracerebral CSF spaces, inflammatory periventricular augmented echogenicity and early microcephaly.

eFigure 2

Ultrasound image of a fetus at 24 weeks’ gestation with fetal ascites and intestinal augmented echogenicity. The mother-to-fetus transmission of human cytomegalovirus (HCMV) following periconceptional maternal primary HCMV infection is confirmed by amniotic fluid testing.