Primary Epstein-Barr virus (EBV) infections during pregnancy are rare because ≥95% of adults have serologic evidence of past infection. Estimates place the risk at 0.0% to 0.2% (10). However, the frequency of primary EBV infection was found to be 7% among 46 pregnant women who were susceptible early in gestation (618). Reactivation of latent EBV is common during pregnancy (10).

The majority of primary EBV-infected individuals are asymptomatic. Infectious mononucleosis is the most common clinical manifestation of infection. Complications such as meningoencephalitis, Guillain-Barré syndrome, airway obstruction, or rupture of the spleen are infrequent, but can be severe (10).

Diagnosis typically is made with serologic tests. Hetero-phile antibodies are usually present in most women at onset of symptoms, and decline to undetectable levels within 3 months. Persistence of heterophile antibodies for as long as one year can occur. The measurement of antibodies to the EBV viral capsid antigens (VCA), early antigen (EA), and EBV nuclear antigen (EBNA) can be used to make a specific diagnosis of primary EBV infection. EBV-VCA IgM is usually present at onset of symptoms. It is rarely detected with EBV reactivations. EBV-VCA IgG is generally present early and four-fold titer rises are detected in 20% or fewer patients. Anti-EA is found in 80% of patients with primary EBV, but it can also be detected with virus reactivations. IgG antibodies to EBNA usually appear after 3 or 4 weeks, and remain detectable indefinitely (619).

Transplacental transmission of EBV is rare. Maternal oropharyngeal EBV shedding may increase the risk of maternal-fetal transmission of HIV-1 (620). EBV acquisition during passage through the birth canal is theoretically possible because cervical shedding of this virus has been demonstrated (10). A study of 100 healthy women showed that 46% of women shed EBV in their breast milk, and that the shedding was highest at 3 to 12 weeks postpartum (621).

A variety of congenital defects have been described in the offspring of women with documented EBV infection or infectious mononucleosis. Abnormalities included low birth weight, micrognathia, congenital heart disease, biliary atresia, cataract, microphthalmia, hip dysplasia, and central nervous system malformations. However, there is no specific pattern to these findings and they likely represent chance occurrences (10).

Human herpesvirus 6 (HHV-6) is an enveloped double-stranded DNA virus that is separated into two variants (HHV-6A and HHV-6B) on the basis of differing genetic, immunologic, and biologic properties (622). Most children become infected by two years of age, but seropositivity decreases with age. Transmission is believed to be by
infected oral secretions, but the virus is also found in the cervices of some pregnant women in late gestation (622,623).

HHV-6 antibodies were found in 100% of 569 pregnant and nonpregnant women attending a family planning clinic in San Antonio, Texas. HHV-6 genital shedding was found in 2% of the pregnant women, and 3.7% of those who were not pregnant (624). A study of pregnant women in Japan similarly found a 100% prevalence of IgG antibodies to HHV-6, and 1.6% of women had significant increases in these titers suggesting virus reactivation. HHV-6 DNA was found in the genital tract of 3.7% of pregnant women in the first trimester and in 12.2% of the same women in their third trimester (625). Serosurveys of other countries show that the prevalence of HHV-6 antibodies can vary from a low of 50% in Morocco, to 76% in France, and 90% in Ecuador and Congo (626).

Roseola infantum is the clinical illness most often associated with HHV-6 (usually HHV-6B) in children, but most symptomatic HHV-6 infections in infants are non-specific febrile illnesses. Primary infection in healthy adults is rare and may manifest with rash, hepatitis, lymphadenopathy, or encephalitis. In immunosuppressed individuals, especially posttransplantation, HHV-6 (usually HHV-6A) reactivates and is associated with pneumonitis and encephalitis. A variety of unproven disease associations such as Bell’s palsy, drug-induced hypersensitivity syndrome, multiple sclerosis, sarcoidosis, and lymphoproliferative disorders have been described for HHV-6 (622).