中国替诺福韦酯治疗儿童慢性乙型肝炎婴儿的长期安全性

StephenW

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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ

StephenW

中国替诺福韦酯治疗儿童慢性乙型肝炎婴儿的长期安全性
潘加仑（Calvin Q Pan）1 2，戴二黑3，段中平4，韩国荣5，赵文静6，王玉明7，张怀红8，朱宝深9，姜洪秀5，张书琴10，张小虎8，邹怀斌4，陈秀丽3，于晨4
隶属关系
隶属关系

    1个
    首都医科大学附属北京地坛医院肝病研究中心，北京[email protected]。
    2个
    美国纽约州纽约大学格罗斯曼医学院纽约州立大学兰格尼分校医学系消化内科和肝病科。
    3
    石家庄市第五医院肝病科，河北石家庄。
    4
    首都医科大学附属北京佑安医院第四肝病中心，中国北京。
    5
    东南大学第二附属医院妇产科，南京。
    6
    吉林省肝胆疾病医院中心实验室，吉林长春
    7
    重庆大学，西南大学公共卫生医院，传染病研究所，陆军医科大学西南医院
    8
    河南省南阳市南阳中心医院感染科
    9
    石家庄市第五医院妇产科，河北石家庄。
    10
    吉林省肝病医院人工肝科，长春

    PMID：33789963 DOI：10.1136 / gutjnl-2020-322719

抽象的

目的：胎儿暴露于替诺福韦富马酸二吡呋酯（TDF）预防母婴传播HBV后，婴儿的身体和神经心理发育仍不确定。我们旨在调查妊娠中期的TDF治疗的安全性。

设计：招募来自先前随机对照试验的婴儿进行我们的长期随访研究。患有慢性乙型肝炎的母亲在妊娠中期随机接受TDF治疗或不接受治疗。使用Bayley-III评估法评估了192周龄婴儿的身体生长或畸形，骨矿物质密度（BMD）和神经发育。

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。

结论：暴露于TDF的婴儿在192周时具有正常的身体生长，BMD和神经发育。我们的发现提供了证据，表明胎儿在接受母体TDF疗法预防乙型肝炎传播后具有长期安全性。

试用注册号：NCT01488526。

关键词：抗病毒治疗；药物毒性乙型肝炎

©作者（或其雇主）2021年。不得将其商业重复使用。查看权限。由BMJ发布