Elsevier

Seminars in Perinatology

Volume 31, Issue 1, February 2007, Pages 10-18
Seminars in Perinatology

Recent Advances in the Prevention and Treatment of Congenital Cytomegalovirus Infections

https://doi.org/10.1053/j.semperi.2007.01.002Get rights and content

Continued but slow progress has led to recent advances in our understanding that congenital cytomegalovirus (CMV) infection has occurred. We understand that the most severe congenital disease occurs following a primary maternal infection during pregnancy. We now have the ability to accurately diagnosis a primary maternal infection using serologic studies of single serum sample. For pregnant women with young children, we know that child-to-mother CMV transmission can probably be prevented by hygienic intervention, and that for pregnant women who have acquired a primary CMV infection, mother-to-fetal transmission is probably preventable using CMV hyperimmune globulin. Although additional studies are needed, treatment of congenitally infected fetuses or newborns should be possible using either CMV hyperimmune globulin or antiviral agents such as ganciclovir or its derivates. Finally, recent evidence indicates that CMV replicates in the placenta, impairs development, and causes inflammation and dysfunction. This plus the reversibility of many manifestations of congenital infection in the fetus and newborn indicate that congenital CMV disease is in part a syndrome of placental insufficiency.

Section snippets

Primary Versus Recurrent Maternal Infection

Nearly all symptomatic congenital infections occur when a woman sustains a primary infection with CMV either during or just before pregnancy.2 Infection appears to be associated with progressively increasing viral transmission rates by gestational age, but infections early in gestation probably result in more severe congenital disease.3, 4 If infection occurs after conception, approximately 50% of fetuses will become infected, and approximately one-half of those will have symptoms at birth.3 If

Prevention of Maternal Infection during Pregnancy

Possible approaches to preventing congenital CMV infections include changes in hygienic behavior for seronegative pregnant women, administration of CMV hyperimmune globulin (HIG) to pregnant women with a primary infection, and vaccines administered to girls or women well before pregnancy.

Two studies were done to determine whether changing protective behaviors prevents child-to-mother transmission of CMV during pregnancy.15, 16 One studied 166 seronegative mothers with a child <36 months of age

Prenatal Therapy

Despite advances in the diagnosis of maternal–fetal CMV infection, an effective therapy is unavailable. Pregnancy termination is often offered as an option when affected or infected fetuses are identified by ultrasonography or amniocentesis, respectively. Recent case reports have focused on the safe administration of oral ganciclovir to mothers of CMV-infected fetuses. An HIV-positive woman was treated with intravenous ganciclovir from 30 to 34 weeks’ gestation, followed by neonatal plasma

Development of the Hemochorial Human Placenta

IUGR associated with congenital CMV disease suggests placental deficiencies. Knowledge of the cellular and molecular processes involved in development of the human placenta is a prerequisite to understanding how infection impairs functions.45 The embryo’s acquisition of a supply of maternal blood is a critical hurdle in pregnancy maintenance. The mechanics of this process are accomplished by cytotrophoblasts, which are specialized epithelial cells of the placenta. Placentation, a stepwise

Acknowledgments

Lenore Pereira laboratory studies were supported by NIH grants AI46657 and AI53782, Thrasher Research Fund grant No. 02821-7, University of California San Francisco Academic Senate. We thank Mary McKenney for editing the manuscript.

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