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Original research
Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China
  1. Calvin Q. Pan1,2,
  2. Erhei Dai3,
  3. Zhongping Duan4,
  4. Guorong Han5,
  5. Wenjing Zhao6,
  6. Yuming Wang7,
  7. Huaihong Zhang8,
  8. Baoshen Zhu9,
  9. Hongxiu Jiang5,
  10. Shuqin Zhang10,
  11. Xiaohu Zhang8,
  12. Huaibin Zou4,
  13. Xiuli Chen3,
  14. Yu Chen4
  1. 1Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
  2. 2Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU Grossman School of Medicine, New York City, New York, USA
  3. 3Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China
  4. 4Hepatology Center Department 4, Beijing Youan Hospital Capital Medical University, Beijing, China
  5. 5Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
  6. 6Central Laboratory, Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, Ji Lin, China
  7. 7Southwest University Public Health Hospital, Institute of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, China
  8. 8Department of Infectious Diseases, Nanyang Center Hospital, Nanyang, Henan, China
  9. 9Department of Gynecology and Obstetrics, The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China
  10. 10Department of Artificial Liver, Hepatology Hospital of Jilin Province, Changchun, China
  1. Correspondence to Professor Calvin Q. Pan, Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Panc01{at}NYU.edu

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.

  • hepatitis B
  • antiviral therapy
  • drug toxicity

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. The data supporting the findings of this study are available from the corresponding author. Anonymized Individual Patient Data (IPD) may be shared with other qualified researchers upon request.

A proposal with a detailed description of study objectives and a statistical analysis plan will be needed for evaluation of the reasonability to request for our data.

Approval of such requests is at investigators' discretion and is dependent on the nature of the request, the merit of the research proposed, the availability of the data, and the intended use of the data. Data requests should be sent to the corresponding author. Data sharing much be approved by the authorities including the institutional review board and National Health Administrations in China.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. The data supporting the findings of this study are available from the corresponding author. Anonymized Individual Patient Data (IPD) may be shared with other qualified researchers upon request.

A proposal with a detailed description of study objectives and a statistical analysis plan will be needed for evaluation of the reasonability to request for our data.

Approval of such requests is at investigators' discretion and is dependent on the nature of the request, the merit of the research proposed, the availability of the data, and the intended use of the data. Data requests should be sent to the corresponding author. Data sharing much be approved by the authorities including the institutional review board and National Health Administrations in China.

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Footnotes

  • Contributors CP conceived the study and designed the trial protocol, obtained the research grant, supervised the trial, analysed the data, wrote the manuscript and addressed all comments of the journal reviewers. All other authors are site investigators and contributed to the collection of clinical and laboratory data. CP and ED performed statistical analyses. All authors reviewed and approved the final version of the manuscript.

  • Funding The current study was supported by a research grant from Gilead Sciences (grant number: IN-US-174-0174-A3). However, this study was designed by the lead author and was independently conducted by the investigators. Clinical data were collected by site research teams. Following database lock and statistical analyses, the lead author drafted the manuscript. All coauthors vouch for the veracity and completeness of the reported data and analyses and have agreed to submit the report for publication.

  • Competing interests CP is a speaker and consultant for Gilead Sciences. He also received a research grant from Gilead Sciences and Assembly Biosciences.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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