Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China
Calvin Q Pan 1 2 , Erhei Dai 3 , Zhongping Duan 4 , Guorong Han 5 , Wenjing Zhao 6 , Yuming Wang 7 , Huaihong Zhang 8 , Baoshen Zhu 9 , Hongxiu Jiang 5 , Shuqin Zhang 10 , Xiaohu Zhang 8 , Huaibin Zou 4 , Xiuli Chen 3 , Yu Chen 4
Affiliations
Affiliations
1
Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China [email protected].
2
Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU Grossman School of Medicine, New York City, New York, USA.
3
Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.
4
Hepatology Center Department 4, Beijing Youan Hospital Capital Medical University, Beijing, China.
5
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China.
6
Central Laboratory, Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, Ji Lin, China.
7
Southwest University Public Health Hospital, Institute of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, China.
8
Department of Infectious Diseases, Nanyang Center Hospital, Nanyang, Henan, China.
9
Department of Gynecology and Obstetrics, The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.
10
Department of Artificial Liver, Hepatology Hospital of Jilin Province, Changchun, China.
PMID: 33789963 DOI: 10.1136/gutjnl-2020-322719
Abstract
Objective: The physical and neuromental development of infants remains uncertain after fetal exposure to tenofovir disoproxil fumarate (TDF) for the prevention of mother-to-child transmission of HBV. We aimed to investigate the safety of TDF therapy during the third trimester of pregnancy.
Design: Infants from a previous randomised controlled trial were recruited for our long-term follow-up (LTFU) study. Mothers with chronic hepatitis B were randomised to receive TDF therapy or no treatment during the third trimester. Infants' physical growth or malformation, bone mineral density (BMD) and neurodevelopment, as assessed using Bayley-III assessment, were examined at 192 weeks of age.
Results: Of 180 eligible infants, 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (control group: 75; TDF-treated group: 70). In the TDF-treated group, the mean duration of fetal exposure to TDF was 8.57±0.53 weeks. Congenital malformation rates were similar between the two groups at week 192. The mean body weight of boys in the control and TDF-treated groups was significantly higher (19.84±3.46 kg vs. 18.47±2.34 kg; p=0.03) and within the normal range (18.48±2.35 kg vs. 17.80±2.50 kg; p=0.07), respectively, when compared with the national standard. Other prespecified outcomes (head circumference, height, BMD, and cognitive, motor, social-emotional, and adaptive behaviour measurements) were all comparable between the groups.
Conclusion: Infants with fetal exposure to TDF had normal physical growth, BMD and neurodevelopment at week 192. Our findings provide evidence on the long-term safety of infants after fetal exposure to maternal TDF therapy for preventing hepatitis B transmission.
Trial registration number: NCT01488526.
Keywords: antiviral therapy; drug toxicity; hepatitis B.
结果：在180名合格婴儿中，有176/180名（98％）入组，并且有145/176名（82％）完成了LTFU（对照组：75名； TDF治疗组：70名）。在TDF治疗组中，胎儿暴露于TDF的平均持续时间为8.57±0.53周。两组在第192周的先天性畸形率相似。对照组和TDF治疗组中男孩的平均体重显着更高（19.84±3.46 kg vs. 18.47±2.34 kg； p = 0.03）并且在正常范围内与国家标准比较时，范围分别为（18.48±2.35 kg和17.80±2.50 kg； p = 0.07）。两组之间的其他预定结果（头围，身高，BMD和认知，运动，社交情感和适应行为测量）均具有可比性。