Review
An Algorithm for Risk Assessment and Intervention of Mother to Child Transmission of Hepatitis B Virus

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Background & Aims

Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)–positive mothers. We analyzed methods of risk assessment and interventions for MTCT.

Methods

We reviewed 63 articles and abstracts published from 1975–2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database.

Results

Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6–12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%–30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (106 copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT.

Conclusions

HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT.

Section snippets

Hepatitis B e antigen

HBeAg is an 18-kDa secretory protein that is postulated to have immunoregulatory functions in the HBV-infected human host.13 In the clinical setting, HBeAg is used as an index for active viral replication and infectivity. Maternal HBeAg may be filtered through the placenta.14, 15 Although HBeAg is present in up to 70% of neonates at birth, only 10% of these infants are actually infected at birth.16 Without HBV viremia, most infants who are HBeAg positive at birth (representing maternal HBeAg)

Hepatitis B Virus Transmission at the Antepartum Stage

Intrauterine transmission is defined as HBsAg in the neonatal blood 1–30 days after birth or detectable HBV DNA in neonatal peripheral venous blood.36 IUT might occur via infected male germline or maternal oocytes in early embryonic stage.20, 28, 37 IUT is not likely prevented by HBIg and HBV vaccine.22 Other mechanisms for IUT include HBV circulating to the fetus via maternal peripheral blood mononuclear cells,38 “cellular transfer” of HBV from cell to cell in the placenta demonstrated by a

Hepatitis B immunoglobulin Injection

Previous reports showed that HBIg induced >2 log drops in maternal HBV DNA with a modest reduction of MTCT rates when administrated during the antepartum stage.46, 47, 48 However, a recent large randomized controlled trial by Yuan et al49 showed that antepartum HBIg use was not effective in preventing MTCT. In addition, all newborns from mothers who received antepartum HBIg were negative for anti-HBs at birth in this study, further challenging the hypothesis that HBIg transferred to the fetus

Summary and Proposal of an Algorithm for the Prevention of Hepatitis B Virus Mother to Child Transmission

The majority of chronic hepatitis B infections, especially in Asians, are due to perinatal transmissions of HBV. Despite passive-active immunoprophylaxis, maternal HBeAg positivity and HBV DNA levels >200,000 IU (6 log10 copies)/mL are correlated with an increased risk of MTCT.9, 12, 27 The transmission risk increases with higher levels of maternal HBV DNA, or if other factors such as threatened preterm labor, prolonged labor, or a prior child with passive-active immunoprophylaxis failure are

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    Conflicts of interest These authors disclose the following: Dr Pan has the following financial relationships with pharmaceutical companies for the past 5 years: he has received research grants from Gilead, Bristol Myers Squibb, Novartis, Idenix, Roche, and Schering-Plough and also serves as a consultant, advisor, and speakers bureau for Gilead, Bristol Myers Squibb, Novartis, Idenix, Roche, Schering-Plough, Onyx, Three Rivers, Salix, Genentech, Vertex, and Pharmasset. Dr Tong is on the speakers bureau for Bristol Meyers Squibb, Gilead, Genentech, Merck, Vertex, and Onyx. The remaining authors disclose no conflicts.

    Funding This manuscript was initially based on the expert consensuses of the First International Symposium on Hepatitis B Infection in Special Population held on April 17–18, 2009 in Beijing, China. The primary writers met again on May 14–15, 2010 in Nan Jing, China, to prepare the final draft with updates. The meetings and manuscript development were supported by the Chinese National Research Grant of the Eleventh Five-Year Plan for the Key Projects in Infectious Diseases (grant no. 2008ZX10002-001).

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