Perinatal Transmission of the Hepatitis B Virus

Strategies for Prevention

William F. Balistreri, MD


June 04, 2015

In This Article

What Are the Risk Factors for Immunoprophylaxis Failure?

Despite timely postexposure prophylaxis, perinatal HBV transmission occurs in 5%-15% of infants. Mothers who are HBsAg- and HBeAg-positive with HBV DNA levels ≥ 106 copies/mL are at greatest risk of transmitting HBV to their infants.

Several prenatal factors have been postulated to be responsible for immunoprophylaxis failure: HBV- infected germ cells, transplacental infection, and invasive prenatal diagnostic tests.[19] Other reported perinatal factors include maternal viral status and mode of delivery. The presence of HBV DNA in cord blood also predicts failure of passive-active immunization.[20] Transmission of HBV is also much more likely to occur if the mother is acutely infected during the third trimester compared with during the first or second trimester (62% vs 1.8%).[21,22]

The risk for perinatal transmission of HBV is almost entirely related to maternal HBeAg positivity or high levels of HBV DNA in serum (> 106 copies/mL) at delivery, assuming that optimal prophylaxis is administered to the infant. This has been confirmed in several studies:

  • Burk and colleagues[8] found a significant relationship between the maternal serum HBV DNA level and the rate of persistent infection in the infant. The likelihood of perinatal HBV transmission was 147-fold higher for HBeAg-positive mothers with an elevated HBV DNA level.

  • Wen and colleagues[23] reported a stepwise increase in the risk for chronic HBV infection in infants born to HBsAg-positive mothers according to the maternal HBV DNA level; the predicted rates of infection at maternal HBV DNA levels of 107, 108, and 109 copies/mL were 7%, 15%, and 28%, respectively, after adjustment for other factors likely to influence transmission.

  • Zhang and colleagues[24] prospectively evaluated the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8-12 months who completed immunoprophylaxis were tested for HBV markers. The immunoprophylaxis failure rate was 3%. Among infants born to HBeAg-positive mothers, breakthrough despite immunoprophylaxis occurred in 8% of the infants who received vaccine plus HBIg and in 17% who received only the vaccine. Infants with immunoprophylaxis failure were all born to mothers with HBV DNA levels ≥ 106 copies/mL.

  • Kang,[25] Alexander,[26] and Towers[27] and their colleagues explored the risk factors associated with their observed immunoprophylaxis failure rate of 4%. They also found the same three risk factors to be associated with failure of HBV immunoprophylaxis: mothers who were positive for HBeAg, maternal HBV DNA level, and lack of HBIg administration.

Conversely, perinatal HBV transmission is unlikely to occur if the mother is anti-HBe-positive or HBeAg-negative, independent of the maternal serum HBV viral load.[28]


Yi and colleagues[29] performed a case/control study on infants who were born to HBsAg-positive mothers without antiviral exposure and had appropriately completed the immunization protocol. They found a higher perinatal HBV transmission rate in infants whose mothers had amniocentesis compared with those who did not undergo amniocentesis.Amniocentesis performed on HBsAg-positive mothers with a serum HBV DNA level ≥ 107 copies/mLincreased the frequency of perinatal HBV transmission (50% vs 4.5%).

Mode of Delivery

Pan and colleagues[30] assessed the risk factors for mother-to-child transmission of HBV in 1409 consecutive newborns born to HBsAg-positive mothers. Overall, passive-active HBV prophylaxis failed in 2.8% of infants, all of whom were born to mothers with predelivery serum HBV DNA levels > 106 copies/mL. A lower transmission rate was found among infants delivered by elective cesarean section (1.4%) compared with those delivered by vaginal delivery or urgent (nonelective) cesarean section (3.4% and 4.2%, respectively). On multivariate analysis, including HBeAg status and maternal serum HBV DNA levels, nonelective cesarean section was a strong independent predictor of perinatal HBV transmission (odds ratio, 4.3). Despite some limitations, this study confirms previously observed rates of reduced transmission of HBV in infants delivered by elective compared with nonelective cesarean section.[2,3,5,30,31]


Pirillo and colleagues[32] documented the absence of significant levels of HBV DNA in the breast milk of HBV-infected women.This observation supports the present recommendations for continued breastfeeding. As opposed to postpartum HIV infection, HBV infection is not a contraindication to breastfeeding, regardless of the maternal HBeAg status or viral load.[11,32] This, of course, assumes that appropriate immunoprophylaxis has been carried out.[33,34,35]


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