Jacquemard and colleagues then proposed a different approach.30 In a small pilot study of 20 patients, these authors used high doses of oral valacylovir (2 g 4 times daily) and documented therapeutic drug concentrations and a decline in CMV viral load in fetal serum. Patients were not stratified by severity of fetal injury at onset of treatment, so the authors were unable to define which fetuses were most likely to benefit from treatment.
In a follow-up investigation, Leruez-Ville and colleagues reported another small series in which high-dose oral valacyclovir (8 g daily) was used for treatment.31 They excluded fetuses with severe brain anomalies and fetuses with no sonographic evidence of injury. The median gestational age at diagnosis was 26 weeks. Thirty-four of 43 treated fetuses were free of injury at birth. In addition, the viral load in the neonate’s serum decreased significantly after treatment, and the platelet count increased. The authors then compared these outcomes to a historical cohort and confirmed that treatment increased the proportion of asymptomatic neonates from 43% without treatment to 82% with treatment (P<.05 with no overlapping confidence intervals).
We conclude from these investigations that hyperimmune globulin is unlikely to be of value in treating congenital CMV infection, especially if the fetus already has sonographic findings of severe injury. High-dose oral valacyclovir also is unlikely to be of value in severely affected fetuses, particularly those with evidence of CNS injury. However, antiviral therapy may be of modest value in situations when the fetus is less severely injured.
Preventive measures
Since no definitive treatment is available for congenital CMV infection, our efforts as clinicians should focus on measures that may prevent transmission of infection to the pregnant patient. These measures include:
- Encouraging patients to use careful handwashing techniques when handling infant diapers and toys.
- Encouraging patients to adopt safe sexual practices if not already engaged in a mutually faithful, monogamous relationship.
- Using CMV-negative blood when transfusing a pregnant woman or a fetus.
At the present time, unfortunately, a readily available and highly effective therapy for prevention of CMV infection is not available.
CASE Congenital infection diagnosed
The ultrasound findings are most consistent with congenital CMV infection, especially given the patient’s work as an elementary schoolteacher. The diagnosis of maternal infection is best established by conventional serology (positive IgM, negative IgM) and detection of viral DNA in maternal blood by PCR testing. The diagnosis of congenital infection is best confirmed by documentation of viral DNA in the amniotic fluid by PCR testing. Given that this fetus already has evidence of moderate to severe injury, no treatment is likely to be effective in reversing the abnormal ultrasound findings. Pregnancy termination may be an option, depending upon the patient’s desires and the legal restrictions prevalent in the patient’s geographic area. ●
Key points on CMV infection in pregnancy
- Cytomegalovirus infection is the most common of the perinatally transmitted infections.
- Maternal infection is often asymptomatic. When symptoms are present, they resemble those of an influenza-like illness. In immunocompromised persons, however, CMV may cause serious complications, including pneumonia, hepatitis, and chorioretinitis.
- The virus is transmitted by contact with contaminated body fluids, such as saliva, urine, blood, and genital secretions.
- The greatest risk of severe fetal injury results from primary maternal infection in the first trimester of pregnancy.
- Manifestations of severe congenital CMV infection include growth restriction, microcephaly, ventriculomegaly, hepatosplenomegaly, ascites, chorioretinitis, thrombocytopenia, purpura, and hydrops (“blueberry muffin baby”).
- Late manifestations of infection, which usually follow recurrent maternal infection, may appear as a child enters elementary school and include visual and auditory deficits, developmental delays, and learning disabilities.
- The diagnosis of maternal infection is confirmed by serology and detection of viral DNA in the serum by PCR testing.
- The diagnosis of fetal infection is best made by a combination of abnormal ultrasound findings and detection of CMV DNA in amniotic fluid. The characteristic ultrasound findings include placentomegaly, microcephaly, ventriculomegaly, growth restriction, echogenic bowel, and serous effusions/hydrops.
- Treatment of the mother with antiviral medications such as valacyclovir may be of modest value in reducing placental edema, decreasing viral load in the fetus, and hastening the resolution of some ultrasound findings, such as echogenic bowel.
- While initial studies seemed promising, the use of hyperimmune globulin has not proven to be consistently effective in treating congenital infection.