Safety and efficacy of telbivudine in late pregnancy to prevent mother‐to‐child transmission of hepatitis B virus: A multicenter prospective cohort study

Abstract

Infection of hepatitis B virus (HBV) occurs in ~10% of infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg) after immunoprophylaxis. We aimed to evaluate the safety and efficacy of telbivudine used during late pregnancy for preventing mother-to-child transmission of HBV. We conducted a multicenter prospective cohort study in 5 hospitals from 2012 to 2014, which enrolled HBV-infected singleton pregnant women with positive HBeAg. By their choice, women were divided into therapy (telbivudine 600 mg/day, from gestation 28-32 weeks to 3-4 weeks postpartum) and control (no antiviral agent) groups. Infants received passive-active immunoprophylaxis and follow-up at the age of 7-14 months. Totally, 328 pregnant women were included: 149 in the telbivudine group and 179 in the control group. Baseline HBV DNA levels were similar in the 2 groups (7.43 vs 7.37 log IU/mL, P = .711). At delivery, HBV DNA levels in the telbivudine and control groups were 3.80 and 7.26 log IU/mL, respectively (P < .0001). Of the infants, 128 (85.9%) in the telbivudine group and 156 (87.2%) in the control group were followed up. No infant in the telbivudine group had chronic infection, while 2 (1.28%) infants in the control group did (P = .503). Three (2.34%) infants in the telbivudine group, but none in the control group, had severe congenital or developmental abnormalities (P = .090). The data indicate that telbivudine may block perinatal HBV transmission. However, larger studies are required to clarify whether anti-HBV therapy in pregnancy is associated with severe adverse effects in the foetuses and infants.

Mother‐to‐child transmission of hepatitis B virus after amniocentesis: A retrospective matched cohort study

“…The incubation period of HBV infection is 30 to 180 days, which means that the current universal neonatal vaccination programs mainly target the peripartum transmission. Many studies as well as our results found that most neonates with HBsAg and/or HBV DNA positivity at birth became seronegative later after the standard infant immunoprophylaxis. The presence of HBsAg and/or HBV DNA at birth may be transient and does not indicate a definite infection; therefore, MTCT was proposed to be defined with infant seromarker measurement at some specific time points, usually at age 6 to 12 months after the HBV vaccination programs .…”

“…The target maternal HBV DNA level at delivery is theoretically as low as possible because of high correlation between MTCT rate and maternal viral loads. Practically, maternal HBV DNA less than 5.0 to 6.0 log 10 IU/mL is considered an anticipated level with minimal risk of MTCT at delivery and the same prior to amniocentesis because MTCT was absent when maternal HBV DNA was less than 7.0 log 10 IU/mL in previous and our studies. Therefore, it is feasible to give at least 4 weeks of antiviral treatment to highly viremic mothers and to achieve an aforementioned target HBV DNA level before amniocentesis.…”

“…High maternal viremia was a risk factor of MTCT after amniocentesis in our cohort. Many recent studies have demonstrated that antiviral therapy during pregnancy with high viral loads can efficiently reduce maternal serum HBV DNA levels and decrease MTCT rates without significant safety concerns. Presumably, administering antiviral treatment to high‐risk women undergoing amniocentesis should be effective for preventing the vertical transmission of HBV.…”

“…Although this trend of decreasing MTCT rates in highly viremic mothers (from 14.29% to 0%) was not statistically significant (possibly explained by the small number of cases), it still suggests that antiviral therapy should be effective for preventing HBV transmission after amniocentesis in mothers with high viral loads. However, it is difficult to determine the ideal treatment regimen considering the optimal time of initiation, appropriate duration, and target maternal HBV DNA level at delivery of antiviral therapy because of heterogeneous study design . To prevent MTCT, some professional societies recommended short‐term maternal antiviral treatment starting from the late second or third trimester up to 0 to 12 weeks after delivery with the threshold of maternal HBV DNA more than 5.0 to 8.0 log 10 IU/mL.…”

Efficacy and safety of antiviral treatment on blocking the mother‐to‐child transmission of hepatitis B virus: A meta‐analysis

“…Of the 32 RCTs that enrolled 4189 pregnant women, 17 studies evaluated the effect of LAM, 15 studies evaluated LdT, 3 studies evaluated TDF, and 3 studies evaluated both LAM and LdT . Of the 27 non‐RCT studies enrolling 5039 pregnant women, 10 evaluated LAM, 18 evaluated LdT, 3 studies evaluated TDF, 2 evaluated both LAM and LdT, and another 2 studies evaluated both LAM and TDF . The characteristics of pregnant women and newborns in the 59 studies are summarized in Table .…”