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Fruit of the Womb
Fruit of the Womb

Cytomegalovirus (CMV): Spectrum of Disease

From the time of exposure to CMV, to the onset of virus excretion, which occurs whether or not symptomatic disease develops, usually takes 4-12 weeks. At least half of the primary, and the vast majority of the recurrent, infections are entirely asymptomatic. Symptomatic infections often mimic 'infectious mononucleosis' (caused by another herpes virus, Epstein-Barr virus) with prolonged fever, often high and spiking, myalgia (muscle ache), arthralgia (joint pain), sore throat, and enlargement of the liver, spleen and lymph nodes. More serious manifestations can occur, but these are fortunately less common and beyond the breadth meaningful to our discussion. Pregnancy by itself does not appear to increase the risk of more severe CMV infections. However, these are more common in immunocompromised women, for example, those with HIV, organ transplants, autoimmune disorders, and cancer. Such patients are at greater risk for more frequent, symptomatic, and severe recurrent CMV infections that may also increase the fetal risk for congenital infections with unexpectedly severe manifestations.

Congenital infections occur in about 1-2% of all pregnancies accounting for 40-50,000 cases per year. Transmission of CMV to the fetus can occur with both primary and recurrent infections despite maternal immunity and has been documented in consecutive pregnancies. Primary maternal infections carry an overall transmission risk to the baby of 25-50% and recurrent infections about 2-3%. Maternal antibody is incompletely protective against transmission to the baby, but it does play a major role in reducing the severity of infection in both fetus and newborn. More than 90% of congenitally infected infants, regardless of the severity of their infection, will shed infectious virus at birth, and may do so for 6 or more years longer, even in the presence of specific immunity.

Congenital CMV infections are asymptomatic or unrecognized in about 90% of cases, including 85-90% of babies acquiring the virus as a consequence of primary maternal infection and 99% of those resulting from recurrent infections. Most of the asymptomatic infections pose no immediate life threat, but 10-15% of these babies are at risk for long-term complications such as sensorineural hearing loss, chorioretinitis, and dental abnormalities, usually apparent by two years' of age. Of these, the hearing loss is by far the most significant because delay in its detection can contribute to psychomotor retardation.

About 5-10% of congenitally infected babies will have significant evidence of infection at birth. Approximately half of these will have classic 'cytomegalic inclusion disease (CMID)' (described below) and half will have atypical involvement. Virtually 100% of these infants excrete CMV at birth and will continue to do so for many years afterwards. Infants in this group have a 20-30% eventual mortality and account for 90% of the significant mental and psychomotor retardation associated with congenital CMV infections. The most severely affected children are usually the result of primary maternal infections during pregnancy and should be suspected in instances of unexplained intrauterine growth restriction and fetal death beyond 20 weeks' gestation.

The most common findings in babies with CMID include symmetrical growth restriction, multiple small skin hemorrhages (petechiae), enlargement of the liver and spleen (hepatosplenomegaly), jaundice, microcephaly (small head), abnormalities of the dental enamel, and chorioretinitis. They can have numerous associated birth defects involving virtually any organ system, a catalog of which is not necessary for our discussion today. Prenatal detection by ultrasound of fetal growth delay and gross or subtle, nonspecific physical abnormalities of the baby may be the only clues that a congenital CMV infection has occurred. Unfortunately, these often manifest themselves only weeks or even months after fetal infection has occurred because the virus is very slow growing, and it is relatively nondestructive, compared to other herpes viruses.

In the final post on CMV, we will focus on diagnosis and counseling...
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