Calvin Q. Pan, M.D., Zhongping Duan, M.D., Erhei Dai, M.D., Shuqin Zhang, M.D., Guorong Han, M.D., Yuming Wang, M.D., Huaihong Zhang, M.D., Huaibin Zou, M.D., Baoshen Zhu, M.D., Wenjing Zhao, M.D., and Hongxiu Jiang, M.D., forthe China Study Group for the Mother-to-Child Transmission of Hepatitis B*
N Engl J Med 2016; 374:2324-2334June 16, 2016DOI: 10.1056/NEJMoa1508660
Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV).
In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28.
At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups. CONCLUSIONS
In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy.
From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) — all in China.
Address reprint requests to Dr. Pan at the Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, NYU School of Medicine, 132-21 41st Ave., Flushing, NY 11355, or at email@example.com.
A complete list of the investigators in the China Study Group for the Mother-to-Child Transmission of Hepatitis B is provided in the Supplementary Appendix, available at NEJM.org.