Telbivudine taken during the second or third trimester of pregnancy reduced the mother-to-infant transmission of hepatitis B to zero in an open-label trial of 88 women who had high viral loads and elevated alanine aminotransferase levels, Dr. Calvin Q. Pan and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.
The authors described their study as the first to examine telbivudine therapy in such patients. They found that the vertical transmission rate was 0% with active treatment and 9% in a control group, despite appropriate immunoprophylaxis of the neonate, said Dr. Pan of the division of liver diseases at Mount Sinai Medical Center, New York, and his associates (Clin. Gastroenterol. Hepatol. 2012 Feb. 16 [doi:10.1016/j.cgh.2012.01.019]).
These results support the idea of using antiviral drugs during pregnancy in women who have chronic hepatitis B virus (HBV) infection to reduce rates of immunoprophylaxis failure in their infants, the investigators noted.
The prospective study involved women treated at a single tertiary-care hospital in Nanjing, China, during 2008-2009. The subjects comprised women at 12-30 weeks’ gestation who had high viral loads, high ALT levels, and were positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg).
The women were not randomly assigned to study groups but instead chose whether to enroll in the antiviral therapy group (53 subjects) or the control group that received only clinical observation (35 subjects). Those in the active treatment group were to receive 600 mg oral telbivudine daily until 28 weeks postpartum.
Mothers who intended to breastfeed were instructed to discontinue the drug before doing so.
The mean duration of exposure to telbivudine was 15 weeks before delivery and 23 weeks postpartum. In all, 13 of the 52 treated mothers (29%) decided to discontinue the antiviral therapy during the first month after delivery, and the rest continued to take it until the study ended at 28 weeks postpartum.
Mean serum HBV DNA levels declined markedly in the treated women but remained steady in the control group. In the intention-to-treat analysis, HBV DNA dropped to undetectable levels in 58% of the telbivudine group but 0% of the control group.
Similarly, ALT levels normalized in 77% of the telbivudine group at 1 month postpartum and in 92% by the end of the study. In comparison, ALT levels normalized in only 49% of the control group at 1 month postpartum and in 71% by the end of the study.
All the infants in the study received hepatitis B immunoglobulin with the HBV vaccine within 6 hours of birth and completed the remainder of the HBV immunizations according to the standard vaccine schedule.
At birth, all infants were HBeAg-positive. Two in the telbivudine group and eight in the control group were HBsAg-positive. And only three infants, all in the control group, had detectable serum levels of HBV DNA.
By week 28, all the infants in the telbivudine group were negative for HBeAg, HBsAg, and HBV DNA. In the control group, three infants remained positive for HBsAg, HBeAg, and HBV DNA, and another five remained positive for HBsAg only.
The primary end point of the study – the rate of mother-to-infant transmission – was 0% (0 of 52 infants) with active treatment and 9% (3 of 32 infants) with no treatment.
In the intention-to-treat analysis, HBV was transmitted to two infants in the telbivudine group (1.9%) and six in the control group (17%).
With regard to safety, there were no significant differences between the two study groups in gestational age at delivery, incidence of maternal peripartum hemorrhage, incidence of premature rupture of membranes, or rate of cesarean delivery. None of the mothers developed hepatitis flares.
The incidence and nature of minor adverse effects among the infants were similar between the two study groups, with no significant differences in birth weight, height, or Apgar scores. There were no congenital deformities and no major adverse effects. All the infants showed normal development through the completion of the study.
During follow-up there were three cases of pneumonia in the telbivudine group and one in the control group. It was not clear whether this difference may have been related to antiviral therapy, the authors said.
They noted that approximately 6% of Asian-American women are HBsAg-positive at perinatal screening, similar to the 7% rate of HBsAg positivity in China. There is no consensus as to the management of these patients because data on antiviral therapy are so limited.
This study lends support to the concept of using antiviral therapy in the second or third trimester in these women, to reduce the failure rate of immunoprophylaxis in their newborns, the researchers said.