Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant

Abstract

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy

Screening for cytomegalovirus during pregnancy

“…The detection of IgM antibodies in maternal sera can be helpful but has problems; although IgM antibodies to CMV occur in all primary infections, they may also occur after reactivations or reinfections and the assay has a high false positive rate. We and others have observed that IgM usually peaks 3 to 6 months after a primary infection but may remain present in serum for over 12 months [36]. Hence, finding IgM to CMV in a single serum of a pregnant woman does not alone establish a recent primary CMV infection during pregnancy [37].…”

On the Possibilities of Laboratory Verification of Cytomegalovirus Infection in Children

“…M. Revello (2002) даны определения понятий, свя-занных с циркуляцией вируса в крови: виремия -при-сутствие вируса в культуре фибробластов эмбриона и диплоидных клеток человека, антигенемия -цир-куляция структурного белка оболочки вируса (рр65) в лейкоцитах периферической крови, ДНК-емия -факт обнаружения ДНК цитомегаловируса в цельной крови (лейкоциты, плазма) количественным мето-дом ПЦР. По данным того же автора, виремия позво-ляет диагностировать первичную инфекцию в 25% случаев, антигенемия -в 50%, и ДНК-емия (лейко-циты) -до 100% в течение первого месяца от начала инфекционного процесса [21]. В исследованиях от-ечественных ученых ДНК цитомегаловируса, свиде-тельствующая об активной стадии инфекции, вери-фицирована в крови у 10-17% детей, поступивших в инфекционный стационар в лихорадочный период острого заболевания [22].…”

Clinical Evaluation of a Chemiluminescence Immunoassay for Determination of Immunoglobulin G Avidity to Human Cytomegalovirus

“…Since symptomatic congenital infections are mostly due to intrauterine transmission following primary maternal infection (4), differential diagnosis of primary versus recurrent infection (or persistence of HCMV-specific immunoglobulin M [IgM] antibody) is crucial for correct counseling and management of pregnancy. The determination of IgG avidity has been shown to help in distinguishing primary from nonprimary HCMV infection (1,8,10), as low avidity values have been shown to be associated to recent primary HCMV infections. Indeed, determination of IgG avidity has become a key step in the algorithm for the interpretation of a positive IgM result in pregnant women (10).…”

“…The determination of IgG avidity has been shown to help in distinguishing primary from nonprimary HCMV infection (1,8,10), as low avidity values have been shown to be associated to recent primary HCMV infections. Indeed, determination of IgG avidity has become a key step in the algorithm for the interpretation of a positive IgM result in pregnant women (10).…”

“…Dating of the onset was based on the presence of abnormal laboratory findings and/or clinical symptoms (10). Persistent IgM antibody was defined as stable IgM values for Ն3 months in the absence of serologic, virologic, or clinical data indicative of a recent primary HCMV infection in the mothers and of congenital infection in the relevant newborn babies.…”