Screening for HBV Infection During Pregnancy
The hepatitis B vaccine was first licensed by the Food and Drug Administration (FDA) in 1981. The following year, the Advisory Committee on Immunization Practices (ACIP) recommended that the vaccine be given as part of an immunoprophylaxis regimen to prevent mother-to-child transmission of hepatitis B virus (HBV). In 1991, these recommendations expanded to include universal hepatitis B immunization for all children, regardless of the mother's hepatitis B surface antigen (HBsAg) status, including the recommendation that all neonates receive hepatitis B vaccine at birth or before discharge from the hospital. Currently, the ACIP, the American College of Obstetrics and Gynecology (ACOG), the American Academy of Family Practice (AAFP), and the American Academy of Pediatrics (AAP) recommend that all pregnant women receive prenatal testing for hepatitis B during each pregnancy by screening serum for the presence of HBsAg, regardless of risk factors or immunization history[2,3]. In addition to screening for prenatal HBsAg in the first trimester, testing should be repeated late in pregnancy for those women who tested negative if they have clinical and laboratory evidence of hepatitis or have ongoing risk for acquiring HBV infection (Figure 1). Pregnant women who present at delivery with unknown HBsAg status should have blood drawn at that time for HBsAg testing. In most states, hepatitis B infection in pregnancy is a reportable condition, and state and local public health departments have programs to provide education and follow-up for HBsAg positive women and their children. Mothers who have a positive HBsAg test should undergo evaluation to determine if they have evidence of chronic liver disease. To facilitate immunoprophylaxis of a woman who is HBsAg seropositive, provide a copy of her laboratory report to her delivery hospital and/or the obstetrical provider that will attend her devlivery, as well as the healthcare provider who will care for her neonate.
Risk of Perinatal HBV Transmission
The overall rate of transmission of HBV from an infected HBsAg-positive mother to her neonate during the perinatal period ranges from 5-90% in the absence of immunoprophylaxis[2,4,5,6,7]. This risk depends on whether the mother also has a positive hepatitis B e antigen (HBeAg) test; those with a positive HBeAg test have a transmission rate of 70-90%, whereas those with a negative HBeAg test have a rate of transmission less than 10%. In these mothers with HBeAg, the risk of HBV perinatal transmission is reduced from 70-90% to approximately 5-15% when the infant receives postnatal immunoprophylaxis with both hepatitis B immune globulin (HBIG) and hepatitis B vaccine series[5,6]; the risk is reduced to approximately 20% with regimens that use multiple doses of HBIG only or the vaccine series alone[1,2,4,5,6]. Although controlled trials have not been performed with HBeAg-negative women, postexposure prophylaxis with HBIG and vaccination would presumably further minimize the risk of transmission.
Route and Timing of Perinatal HBV Transmission
The precise mechanism of HBV transmission remains unclear, but it appears that infection may occur intrapartum or, rarely, in utero. Hepatitis B viral DNA and HBsAg have been detected in amniotic fluid, placental cells, and vaginal secretions of HBsAg-positive women during pregnancy and in cord blood of their neonates[7,8,9,10]. The mode of delivery (vaginal versus caesarean) does not appear to have an impact on the risk for perinatal HBV infection. Transmission of HBV through breast milk is not a significant source of infection, as demonstrated by several small studies performed before the era of routine neonatal prophylaxis[12,13]. The relatively high efficacy of postnatal immunoprophylaxis corresponds with the theory that most mother-to-child HBV transmission presumably occurs during or shortly before delivery.
Prevention in Utero and During Delivery
The occurrence of breakthrough infections despite appropriate immunoprophylaxis, especially among children born to mothers with hepatitis B e antigen, has prompted investigators to explore additional methods for preventing vertical transmission, including administering HBIG,or lamivudine (Epivir-HBV), or both during pregnancy. Published studies evaluating the efficacy of these treatments for the prevention of perinatal HBV infection have shown reductions in HBV DNA levels and decreased rates of infection among infants born to treated mothers, but these studies used non-standard perinatal prophylaxis methods or had a small sample size[14,15,16,17,18]. Accordingly, further studies are needed to evaluate treatment in HBsAg-positive women, particularly those who also have a positive HBeAg and/or high HBV DNA levels. Few published studies have evaluated the risk of intrauterine infection associated with amniocentesis, but since HBV DNA has been detected in amniotic fluid and placental tissue, amniocentesis should be avoided if possible[19,20].
Management of Neonates
The 2005 ACIP recommendations regarding immunoprophylaxis to prevent HBV infection of neonates differ depending on the HBsAg status of the mother . Note that single-antigen hepatitis B vaccine should be used for the birth dose and this dose is considered part of post-exposure prophylaxis for intrapartum exposure to HBV. The HBsAg-containing combination vaccines can be used for subsequent doses given to children six weeks of age and older.
Low Birth Weight and Preterm Infants
Until 2003, the AAP routinely recommended that the birth dose of hepatitis B vaccine for preterm and low birth weight infants born to HBsAg negative mothers be delayed until the child weighed 2000 grams or reached two months of chronological age. Subsequent studies in the United States, Europe and the Middle East indicated that three doses of hepatitis B vaccine in medically stable, preterm, low birth weight, and very low birth weight infants provide protective levels of hepatitis B surface antibody (anti-HBs) that are comparable to full term infants. Based on these more current data, the AAP now recommends that children born to HBsAg negative mothers should receive the first dose of hepatitis B vaccine as early as 30 days of chronological age, regardless of gestational age or birth. In addition, the AAP recommends that if the infant has shown consistent weight gain leading to hospital discharge prior to 30 days of age, the first dose of hepatitis B vaccine should be given at the time of hospital discharge. The remaining doses of the hepatitis B vaccine series should be completed on the same schedule as for full term infants, making sure the second dose is given at least 30 days after the initial dose (Figure 5). Once immunity develops from immunization, protective antibody persists for at least 10 years[22,23]. Currently, the ACIP does not recommend routine booster doses of hepatitis B vaccine for individuals immunized in childhood[1,2].
Impact of Perinatal HBV Transmission
Unlike adults who have a high rate of spontaneous clearance of HBV following acute infection, approximately 90% of children infected during the perinatal period develop chronic infection, and up to 25% will develop chronic active hepatitis as adults. Susceptible children not infected in the perinatal period are at risk for infection from horizontal transmission of HBV in the first five years of life.