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High HBV Viral Load and HBeAg Positive Status Increase Risk of Mother-to-child Hepatitis B Transmission Despite Vaccine

Women with hepatitis B virus (HBV) infection who were hepatitis B "e" antigen (HBeAg) positive and had high HBV DNA viral load during pregnancy were more likely to transmit the virus to their infants, even though the babies received HBV prophylaxis, according to a Canadian study described in the June 11, 2010 advance online edition of the Journal of Viral Hepatitis.

Guidelines recommend that babies born to women with chronic hepatitis B should receive the first dose of the HBV vaccine series immediately after birth; anti-HBV antibodies (hepatitis B immunoglobulin, or HBIG) may also be used. These steps dramatically reduce the risk of vertical transmission, but a small proportion of children become infected even with immuno-prophylaxis.

A.E. Singh from the University of Alberta and colleagues performed a case-control study to analyze maternal factors contributing to mother-to-child HBV transmission to infants receiving adequate prophylaxis.

The researchers compared blood samples blood drawn before delivery from hepatitis B surface antigen (HBsAg) positive mothers whose infants developed HBV infection despite immuno-prophylaxis (cases) and those whose babies remained uninfected (controls).

The analysis included 12 transmission cases and 52 controls selected from a provincial registry between 2000 and 2005. At the time of prenatal screening, the mothers had a median age of 31 years and were a median 12 weeks into pregnancy. The researchers looked at levels of HBsAg, HBeAg, and HBV DNA; HBV genotype was determined for samples with detectable viral load.

Results

• Women who transmitted HBV to their infants were significantly more likely than control women to test positive for HBeAg (77.8% vs 23.1%; P < 0.05).
• Among the 51 mothers with detectable HBV DNA, cases had a significantly higher median viral load than controls (5.6 x 10(8) IU/mL vs 1750 IU/mL; P < 0.0001).
• Looking at the 2 HBeAg negative case women who transmitted the virus, 1 had undetectable viral load 8 months prior to delivery and carried the sP120T mutation, while the other had a viral load of 14 000 IU/mL.
• Overall, a majority of HBV isolates were either genotype B (31.3%) or C (31.3%), with no significant differences in genotype distribution between the case and control women.

Based on these findings, the study authors concluded, "In this case-control study, transmission of HBV to infants was more likely to occur in mothers positive for HBeAg and with high HBV DNA."

These results suggest that therapy to reduce HBV viral load before or during pregnancy may further reduce the risk of mother-to-child transmission.

Investigator affiliations: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Ontario, Canada; National Microbiology Laboratory, Winnipeg, Manitoba, Canada; Provincial Laboratory for Public Health, Edmonton, Alberta, Canada.

7/16/10

Reference

AE Singh, SS Plitt, C Osiowy , and others. Factors associated with vaccine failure and vertical transmission of hepatitis B among a cohort of Canadian mothers and infants. Journal of Viral Hepatitis (Abstract). June 11, 2010 (Epub ahead of print).