Cytomegalovirus (CMV) is the most common congenital viral infection, with intrauterine infection occurring in 0.2% to 2.5% of live births. CMV is a ubiquitous DNA herpes virus, with approximately 50% of the US population having antibodies to CMV. Transmission occurs through direct contact with infected saliva, semen, cervical and vaginal secretions, urine, breast milk, or blood products. Vertical transmission can occur transplacentally, during delivery, or postpartum. An estimated 40,000 infants are born with CMV infection in the United States annually.

Maternal infection: In immunocompetent adults, CMV infection is typically silent. Symptoms, however, can be flu-like, including fever, malaise, swollen glands, and rarely hepatitis. After the primary infection, the virus becomes dormant, with periodic episodes of reactivation and viral shedding.

Congenital (fetal) infection: Most fetal infections are due to recurrent maternal infection and lead to congenital abnormalities in approximately 1.4% of cases. Previously acquired maternal immunity confers protection from clinically apparent disease by maternal antibodies. Mothers determined to be seronegative for CMV before conception or early in gestation have a 1% to 4% risk of acquiring the infection during pregnancy and 30% rate of fetal transmission after seroconversion.

There is no effective in utero therapy for CMV. Because it is difficult to predict the severity of sequelae, counseling patients appropriately about pregnancy termination is problematic. Limited studies have suggested a role for hyperimmunoglobulin therapy, while use is limited to a case-by-case base until further research confirm that benefits outweigh risks. Use of antiviral drugs in immunocompetent individuals is not indicated. The majority of infected fetuses do not suffer serious sequelae. The benefits of breast-feeding outweigh the risk of infection transmission by breastfeeding and may be encouraged.

Primary varicella infection is estimated to affect only 1 to 5 of every 10,000 pregnancies. Less than 2% of cases occur in adults, but this group represents 25% of mortality from varicella zoster virus (VZV). Herpes zoster is also uncommon in women of childbearing age.

The major mode of transmission is respiratory, although direct contact with vesicular or pustular lesions may also result in disease. In the past, nearly all persons were infected before adulthood, 90% before age 14 years. Since the advent of varicella vaccine, most people in the United States have vaccine-induced immunity.

Varicella outbreaks occur most frequently during the winter and spring. The incubation period is 10 to 21 days. Infectivity is greatest 24 to 48 hours before the onset of rash and lasts 3 to 4 days into the rash. The virus is rarely isolated after the lesions have crusted over.

Maternal: The characteristic pruritic rash starts as macules, evolves into papules, and then vesicles. Primary varicella infection tends to be more severe in adults than in children and can be especially severe in pregnancy. A particularly morbid complication of VZV in pregnancy is varicella pneumonia. Maternal mortality with varicella pneumonia may reach 40% in the absence of antiviral therapy (3% to 14% with antiviral therapy). In contrast, herpes zoster infection (reactivation of varicella) is more common in older and immunocompromised patients and poses little risk to the fetus.

Congenital: Fetal infection with varicella zoster can occur in utero, intrapartum, or postpartum. Intrauterine infection infrequently causes congenital abnormalities including cutaneous scars, limb reduction anomalies, malformed digits, muscle atrophy, growth restriction, cataracts, chorioretinitis, microphthalmia, cortical atrophy, microcephaly, and psychomotor retardation.

Varicella exposure during pregnancy: An IgG titer should be obtained within 24 to 48 hours of exposure to a person with noncrusted lesions. The presence of IgG reflects prior immunity, whereas absence of varicella IgG indicates susceptibility.

Varicella zoster immune globulin (VZIG) may be administered to susceptible women (i.e., women without detectable varicella IgG) within 72 hours of exposure to reduce the severity of maternal infection. VZIG is administered intramuscularly (IM) at a dose of 125 U/10 kg to a maximum of 625 U. Maternal administration of VZIG, however, does not ameliorate or prevent fetal infection.

Usually, the disease course is similar in pregnant and nonpregnant patients. Supportive care with fluids and analgesics should be administered. In addition, oral acyclovir, when started within 72 hours of symptom onset, has been shown to be associated with faster healing of lesions, shorter fever times, and less progression to pneumonia. It has low rates of teratogenicity, and its use is recommended by the American College of Obstetricians and Gynecologists (ACOG).

Varicella pneumonia is a medical emergency with significant risk for mortality. Patients should be admitted to the hospital for treatment with intravenous (IV) acyclovir. Acyclovir administered to pregnant women with varicella pneumonia during the second or third trimester decreases maternal morbidity and mortality. The dosage of acyclovir is 10 to 15 mg/kg IV every 8 hours for 7 days, or 800 mg by mouth (PO) five times per day. Tocolytics are generally avoided in women with varicella pneumonia. Delivery should be performed for obstetric indications.

Parvovirus B19 is a single-stranded DNA virus passed primarily by respiratory secretions. Also known as erythema infectiosum or fifth disease, it commonly occurs in school-aged children. By adulthood, 30% to 60% of women have acquired immunity (IgG) to the virus. Outbreaks usually occur in the midwinter to spring months. Prevalence in pregnancy is approximately 3.3% and is highest among teachers, day care workers, and homemakers.

Maternal: Adults may present with typical clinical features: a red, macular rash and facial erythroderma, which gives a characteristic “slapped cheek” appearance. The rash may also cover the trunk and extremities. Infected adults often have acute joint swelling, usually with symmetric involvement of peripheral joints. The arthritis may be severe and chronic. Cases may also present with constitutional symptoms of fever, malaise, myalgia, and headaches. Some adults have a completely asymptomatic infection. Parvovirus B19 preferentially affects rapidly dividing cells and is cytotoxic to erythroid progenitor cells. It may cause aplastic crisis in patients with chronic anemia (e.g., sickle cell disease or thalassemia).

Congenital: Approximately one third of maternal infections are associated with fetal infection via transplacental transfer of the virus. Infection of fetal red blood cell precursors can result in fetal anemia, which, if severe, leads to nonimmune hydrops fetalis. Hydrops can lead to rapid fetal death or can resolve spontaneously. In cases of mild to moderate hydrops, approximately one third resolves; this number decreases in cases of severe hydrops. The likelihood of severe fetal disease is increased if maternal infection occurs during the first 18 weeks of pregnancy, but the risk of hydrops fetalis persists even when infection occurs in the late third trimester. Fetal IgM production after 18 weeks’ gestation probably contributes to the resolution of infection in fetuses who survive. The overall risk of fetal death after maternal infection before 20 weeks is 6% to 11% and after 20 weeks’ gestation is <1%. Parvovirus B19 infection has not been directly associated with specific congenital abnormalities.

No specific antiviral therapy exists for parvovirus B19 infection. IV gamma globulin may be administered on an empiric basis to immunocompromised patients with known exposure to parvovirus B19 and should be used for treatment of women in aplastic crisis with viremia.

Parvovirus B19 can infect the fetal bone marrow, which may lead to severe fetal anemia. Therefore, when maternal infection is confirmed, serial screening sonograms should be performed to assess for fetal signs such as hydrops. Hydrops fetalis usually develops within 6 weeks but can develop as late as 10 weeks after maternal infection. Fetal middle cerebral artery (MCA) Doppler evaluation can be used to predict fetal anemia. Weekly or biweekly ultrasonographic scans can be useful.

If severe anemia is suspected based on ultrasound findings, then fetal hemoglobin levels may be determined with percutaneous umbilical vein sampling. Intrauterine blood transfusion can be used to correct fetal anemia and hydrops. Single or serial intrauterine transfusions may be undertaken.

Despite widespread immunization programs in the United States, the Centers for Disease Control and Prevention (CDC) reports 10% to 20% of adults remain susceptible to rubella. The annual number of reported cases in the United States, however, remains extremely low, with fewer than 10 cases of congenital rubella occurring annually. The disease remains endemic in many areas of the world, and positive rubella antibodies in individuals from these areas can represent active infection.

Maternal: Rubella usually presents as a maculopapular rash that persists for 3 days; generalized lymphadenopathy (especially postauricular and occipital), which may precede the rash; transient arthritis; malaise; and headache. Rubella typically follows the same mild course in pregnancy and may be asymptomatic. The majority of women with affected infants report no history of a rash during their pregnancies.

Congenital: Maternal viremia leads to fetal infection in 25% to 90% of cases. Fetal sequelae are dependent on gestational age, with 90% of first-trimester exposures resulting in clinical signs, 54% at 13 to 14 weeks, and 25% by the end of the second trimester. Congenital rubella syndrome involves multiple organs. The most common manifestations are sensorineural hearing loss, developmental delay, growth retardation, and cardiac and ophthalmic defects.

As many as one third of asymptomatic exposed infants may develop late manifestations, including diabetes mellitus, thyroid disorders, and precocious puberty. The extended rubella syndrome (progressive panencephalitis and type 1 diabetes mellitus) may develop as late as the second or third decade of life.

If a pregnant woman is exposed to rubella, serologic evaluation is recommended. If primary rubella is diagnosed, the mother should be informed about the implications of the infection for the fetus including the high rate of fetal infection and the option for termination discussed. Women electing to continue the pregnancy may be given immune globulin, which may modify clinical rubella in the mother. Immune globulin, however, does not prevent infection or viremia and affords no protection to the fetus.