Hepatitis Viruses
Pablo J. Sánchez
Jane D. Siegel
HEPATITIS A
Maternal infection with hepatitis A virus (HAV) in early pregnancy may result, on rare occasions, in prematurity and spontaneous abortion. It has not been associated with increased rates of congenital malformation or intrauterine growth retardation. Pregnant women with HAV hepatitis generally do not transmit the infection to their offspring because the associated viremia is transient and low grade.
These infants, however, are at risk of acquiring infection during delivery if the mother has jaundice or had acute hepatitis within the 2 weeks before and 1 week after delivery. Most infected infants are asymptomatic and exhibit only mild elevations in transaminase levels. Rarely do nausea, vomiting, anorexia, fever, jaundice, and dark urine occur in infancy. The detection of anti-HAV IgM acutely and the persistence of anti-HAV IgG beyond 18 months of age is diagnostic of neonatal infection. Because transmission of hepatitis A to the neonate is rare, routine serologic studies are not recommended for the asymptomatic infant. Exposed infants may receive 0.02 mL/kg of immune globulin intramuscularly as soon as possible after delivery, even though efficacy has not been established. The infant is potentially infectious for 6 weeks and is maintained in contact precautions if hospitalized during this period. Meticulous attention to hand hygiene when handling soiled diapers is stressed.
The nosocomial transmission of hepatitis A within a nursery is rare because of the relatively brief duration and low titer of viral shedding within the stool. However, immunologically immature preterm infants may excrete HAV antigen and RNA for 4 to 5 months after the acute infection. The source infants in reported nursery outbreaks acquired HAV by vertical transmission from the mother in the perinatal period or by transfusion of blood collected from an asymptomatic donor during the brief viremic phase.
Two inactivated HAV vaccines are currently licensed in the United States for use in high-risk individuals 1 year of age or older.
HEPATITIS B
Hepatitis B virus (HBV) is a 42-nm, double-shelled DNA virus. The inner core consists of hepatitis B core antigen, hepatitis Be antigen (HBeAg), DNA, and DNA polymerase. The outer shell is composed of hepatitis B surface antigen (HBsAg).
Epidemiology
In approximately 5% to 10% of adults with acute HBV hepatitis, a chronic HBsAg carrier state develops. HBeAg is found in the serum of some individuals who are HBsAg-positive, and this identifies an infected individual who is at increased risk of transmitting HBV. In the United States, 5% to 8% of the population have been infected with HBV, and 0.2% to 0.9% have chronic infection. In the absence of prophylaxis, 90% of infants delivered of women who are positive for HBsAg and HBeAg become infected. If the HBsAg-positive mother is HBeAg-negative or has antibody to HBeAg, only 25% or 12% of infants, respectively, become infected.
The vertical transmission of HBV occurs when the mother has acute hepatitis B infection during the third trimester or within the first 2 months postpartum, or if the mother is a chronic HBsAg carrier. Ninety-five percent of neonatal infections occur at the time of delivery from the infant’s exposure to infected maternal blood or cervical and vaginal secretions. Approximately 5% of neonatal hepatitis B infections are transmitted transplacentally, presumably as a result of leakage of infected maternal blood into fetal circulation. HBV infection is not associated with congenital defects or fetal malformations. If perinatal infection does not occur, the infant may be at risk for subsequent infection from close contact with household members who are infected or are chronic carriers.
Clinical Manifestations and Complications
Neonatal infection usually is asymptomatic, with only mild elevation of transaminase levels, although chronic hepatitis B infection with or without cirrhosis, chronic persistent hepatitis, and fatal fulminant hepatitis can occur. Infected infants usually do not become HBsAg-positive until several weeks after birth. Approximately 90% of infants infected perinatally become chronic HBV carriers, and one in four infants who become chronic carriers develops cirrhosis or hepatocellular carcinoma. A 275-fold increase in the risk of developing hepatocellular carcinoma occurs during the third and fourth decades in chronic carriers. This risk is greatest for carriers who acquired the infection perinatally. Transmission from infants and young children occurs within households but is rare in child-care centers.
Prevention
Effective prophylaxis of HBV infection has been possible since licensure of the first HBV vaccine in 1982. Both the highly purified vaccine prepared from human plasma (Heptavax B, Merck and Co., West Point, PA; licensed but no longer available in the United States) and the recombinant DNA vaccines (Recombivax-HB, Merck and Co., West Point, PA; Engerix-B, GlaxoSmithKline Biologics, Rixensart, Belgium) are safe, are highly immunogenic (greater than 95%), and have an efficacy of 90% to 95% in neonates. The concentration of HBsAg protein differs in the two vaccines; the pediatric formulation of Recombivax-HB contains 5 μg/0.5 mL, whereas Engerix-B has 10 μg/0.5 mL. The two vaccines are interchangeable within an immunization series. Previously, for high-risk situations (e.g., infant born to HBsAg-positive or HBsAg-unknown mother), 5 μg of Recombivax was given, whereas 2.5 μg was administered to infants born to HBsAg-negative mothers. For ease of administration, the newly recommended dose of Recombivax
is 5 μg, irrespective of maternal HBsAg status. Similarly, the dose of Engerix-B in infants is always 10 μg, irrespective of maternal risk factors. Recently, recombinant hepatitis B vaccine has been a component of some combination vaccines with excellent immunogenicity demonstrated. However, only single-antigen hepatitis B vaccine can be used for the birth dose. Single-antigen or combination vaccine containing hepatitis B vaccine may be used to complete the series.
is 5 μg, irrespective of maternal HBsAg status. Similarly, the dose of Engerix-B in infants is always 10 μg, irrespective of maternal risk factors. Recently, recombinant hepatitis B vaccine has been a component of some combination vaccines with excellent immunogenicity demonstrated. However, only single-antigen hepatitis B vaccine can be used for the birth dose. Single-antigen or combination vaccine containing hepatitis B vaccine may be used to complete the series.
Traditional risk factors of blood exposure, multiple sex partners, and intravenous drug use may identify only 30% to 60% of individuals infected with HBV. Therefore, the Centers for Disease Control and Prevention recommend universal screening for HBsAg early in pregnancy. Testing should be repeated late in pregnancy for women who are negative initially and at high risk for HBV infection or who have had clinical hepatitis since screening was performed.
Perinatal transmission is prevented in greater than 90% of cases by intramuscular administration of 0.5 mL of hepatitis B immune globulin (HBIG) and hepatitis B vaccine to both term and preterm infants of HBsAg-positive mothers as soon as possible, but within 12 hours of birth. In institutions with policies for universal immunization of infants at birth, HBsAg-positive women still should be identified before delivery because of the addition of HBIG to the immunoprophylaxis regimen for their infants. HBV vaccine is administered intramuscularly and concurrently with HBIG but at a separate anatomic site. In infants with birth weight greater than or equal to 2 kg, the administration of HBV is repeated at 1 month and 6 months of chronologic age. In infants with birth weight less than 2 kg, the initial dose of hepatitis B vaccine does not count for the required three-dose schedule. These infants should receive HBV at 1, 2 to 3, and 6 to 7 months of chronologic age. HBsAg may be detected for 1 week or less after a dose of vaccine. An HBsAg-positive result at any other time indicates a prophylaxis failure or in utero infection, and the infant should not receive additional doses of HBIG or vaccine. Testing for anti-HBs and HBsAg is recommended at 9 to 15 months of age, but not before 9 months of age to avoid detection of anti-HBs from HBIG administered at birth. The presence of anti-HBs and absence of HBsAg indicates successful prophylaxis and immunization. Infants who are negative for anti-HBs (less than 10 mIU/mL) and HBsAg should receive three additional doses of vaccine at 2-month intervals, followed by retesting for anti-HBs 1 month after the third dose. Alternatively, additional doses of vaccine (one to three) can be administered, and the infant can be tested for anti-HBs 1 month after each dose to determine if subsequent doses are needed. Protection from immunization persists for at least 15 years. Household members and sexual contacts of HBsAg-positive mothers should be screened, and if no evidence exists of previous HBV infection, they also should be immunized.
Infants delivered by HBsAg-positive women are bathed as soon as possible after delivery to remove all maternal blood and secretions. Intramuscular injections should be delayed until bathing is completed; if this is not possible, then meticulous cleaning of the site with alcohol is necessary. These infants require standard precautions. Infants born to HBsAg-positive mothers may breast feed, and there is no need to delay the imitation of breast feeding until after the infant is immunized. Although HBsAG has been detected in breast milk from HBsAg-positive women, breast feeding does not increase significantly the risk of transmission of hepatitis B infection.