The management of hepatitis B virus (HBV) infection in pregnancy is complex. Because infection with HBV in infancy often leads to chronic disease, prevention of perinatal, or vertical, transmission is a worthy goal; yet, prophylactic therapy during pregnancy is not well studied. This article explores the consequences of HBV infection during pregnancy, the specific risks imposed by high viral load, the evidence to support preemptive antiviral therapy, and the timing of therapy during pregnancy.
Perinatal transmission is the most common mode of HBV transmission worldwide; however, the maternal screening programs and universal vaccination in newborns with active and passive immunoprophylaxis have dramatically reduced HBV transmission rates. According to recent data from the US Centers for Disease Control and Prevention, prenatal screening for hepatitis B surface antigen (HBsAg) in the United States is nearly universal; 97% of pregnant women undergo screening before delivery.1 Further, among infants at risk of acquiring HBV infection, 92% complete the three-dose vaccination series by the time they are 3 years old. There is some nationwide variation, however, in the appropriate administration of immunoprophylaxis to infants exposed perinatally, ranging from 78% in Louisiana to 99.8% in one California health maintenance organization.2
Perinatal transmission of HBV infection has declined steadily in the United States over the past 2 decades, consistent with the successful implementation of universal screening of pregnant women and vaccination policies.3 Outside the United States, however, many high-prevalence countries lack vaccination coverage and perinatal transmission is common. In 87 countries with a prevalence of HBV infection that exceeds 8%, the infant vaccine coverage was only 36%.4
Risk of chronic infection
The risk of progression to chronic HBV infection is inversely proportional to the age at which the infection was acquired. Without immunoprophylaxis, up to 90% of infants born to hepatitis B e antigen (HBeAg)-positive mothers become HBV carriers. In comparison, 20% to 30% of children infected between age 1 year and 5 years, and fewer than 5% of immunocompetent adults, become HBV carriers.5–7
If the mother is positive for both HBsAg and HBeAg and her baby does not receive immunoprophylaxis, the risk of the baby developing chronic HBV infection by age 6 months is 70% to 90%.8–10 Of those exposed in early childhood, 28.8% are HBsAg positive by age 4 years.5 These data underscore the need for early vaccination.
In a study of 402 HBsAg-positive pregnant women in China, Xu et al11 found that 3.7% of their newborn infants were HBsAg positive within 24 hours of birth. Of the women who were HBeAg positive, the intrauterine infection rate was 9.8%. Analysis of placental tissue for HBsAg, hepatitis B core antigen (HBcAg), and viral load (HBV DNA) uncovered an overall placental infection rate of 44.6%.
Transplacental transmission of HBV has been observed in multiple studies, especially when mothers are positive for HBsAg and HBeAg and have high viral loads. Among mothers positive for HBeAg, Burk et al12 found an odds ratio of 147 for a persistently infected infant when the maternal HBV DNA level was at least 1.4 ng/mL compared with less than .005 ng/mL. Among the HBeAg-negative mothers, the odds ratio for a persistently infected infant was 19.2 with high versus low maternal HBV DNA levels.
Importance of maternal viremia
Despite successful screening and vaccination programs, high maternal HBV DNA correlates in some studies with perinatal transmission. Wiseman et al13 studied 298 chronically HBV-infected women and their infants, who were tested for HBV at age 9 months. Interim analysis showed a transmission rate of 8.5% for infants born to mothers with virus levels greater than 8 log10 copies/mL. These data suggest that perinatal transmission may still be occurring despite the use of effective active and passive immunoprophylaxis. Additional studies are needed to assess the potential risk reduction associated with treatment of high maternal viremia during pregnancy.
Maternal HBV DNA positivity was associated with a high rate of intrauterine transmission of HBV in a program in India in which 11,524 woman were screened for HBV infection.14 Babies of the 133 women found to be positive at the time of birth were screened for HBsAg, HBeAg, and HBV DNA in serum and cord blood. Of 127 deliveries in which the mothers were positive for HBV DNA, 66% of infants had HBV DNA in their cord blood and 41% had serum markers that were positive at birth. Maternal HBV DNA greater than 1.5 X 105 copies/mL was significantly associated with intrauterine transmission (P = .025), whereas mode of delivery and maternal HBeAg status were not. This study adds to the concern that in some cases, the vaccine and hepatitis B immune globulin (HBIg) given at the time of birth may not prevent infection in those born already infected and further supports the need to assess the treatment of pregnant women with high viral titers.