266
Long-Term Safety of Fetal Exposure to Tenofovir
in Infants from Hepatitis B Mothers
Calvin Q. Pan1, Zhongping Duan2, Er Hei Dai3, Guo-Rong
Han4, Shu Qing Zhang5, Yuming Wang6, Huai Hong Zhang7,
Bao Shen Zhu8, Suwen Li8, Hong-Xiu Jiang4, Yi Ding4, Wen
Jing Zhao9, Shi Lian Li10, Xiao Hu Zhang7 and Huai Bin Zou2,
(1)Division of Gastroenterology and Hepatology, New York
University Langone Health, (2)Artificial Liver Center, Beijing
Youan Hospital, (3)The Fifth Hospital of Shijiazhuang, (4)
Department of Gynecology and Obstetrics, The Second
Affiliated Hospital of the Southeast University, (5)Department
of Artificial Liver, Hepatobiliary Disease Hospital of Ji Lin
Province, (6)Institute for Infectious Diseases, Southwest
Hospital, Army Medical University, (7)Department of Medicine,
Nanyang Center Hospital, (8)Department of Gynecology and
Obstetrics, The Fifth Hospital of Shijiazhuang, (9)Central
Laboratory, Hepatobiliary Disease Hospital of Ji Lin Province,
(10)Institute for Infectious Diseases, Southwest Hospital
Background: Randomized-trial data on the long-term effects
on infants’ physical growth and neurodevelopment of the use
of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B
(CHB) mothers are lacking. Methods: All 180 infants who
completed the IN-US174-0174 study were offered participation
in a long- term follow-up (LTFU) study.1 They were from CHB
mothers who were randomly assigned (1:1 ratio) to receive
usual care without antiviral therapy or to receive TDF from
30 to 32 weeks of gestation until postpartum week 4. For
the LTFU study, infants were assessed at the ages of 72,
120 and 192 weeks for growth and neurodevelopment with
Bayley-III measurement. Their bone mineral density (BMD)
was measured at week 192. The neurodevelopmental delay
was defined by cognitive and language composite scores
<85 (1 SD below the mean of 100).2 These parameters
were compared between the TDF-exposed and TDFunexposed
groups. Results: Among 180 infants completed
in the initial study, 176 (98%) participated in the LTFU study
and 144 (82%) completed the LTFU. In the TDF-exposed
group, the mean (±SD) duration of fetal exposure to TDF
was 8.57±0.53 weeks. The gestational age, delivery mode,
weight, height, and Apgar score at birth were similar in the
two groups. At week 192, there was no significant difference
in the pre-specified outcomes between groups including head
circumference, height, BMD, cognitive, social-emotional
and adaptive behavior measurements between groups.
There was no neurodevelopmental delay in the cohort. In the
TDF-exposed group, children had significantly higher motorcomposite
scores (146.46±6.39 vs 142.88±9.54; p=0.009) and
boys had significantly lower mean body weight (18.48±2.35kg
vs 19.84±3.46kg; p= 0.029). However, the boys’ mean body
weight in the TDF-exposed group was significantly higher
than that of the national Chinese reference value of 4-year-old
boys (18.48±2.35kg vs 16.64±1.89; p=0.010).3Conclusion:
Among infants with fetal exposure to TDF, the physical
growth, BMD, and neurodevelopment were similar to those
without the exposure and within the normal range of Chinese
reference values during 192-week follow-up. Our data support
the safety of using TDF during the third trimester in mothers
with CHB. Acknowledgment: (Funded by Gilead Sciences;
ClinicalTrials.gov number, NCT01488526.) References: Pan
CQ, Duan Z, Dai E, et al. Tenofovir to Prevent Hepatitis B
Transmission in Mothers with High Viral Load. N Engl J Med
2016;374:2324-34. Johnson S, Moore T, Marlow N. Using the
Bayley-III to assess neurodevelopmental delay: which cut-off
should be used? Pediatr Res 2014;75:670-4. Li H. [Growth
standardized values and curves based on weight, length/
height and head circumference for Chinese children under 7
years of age]. Zhonghua Er Ke Za Zhi 2009;47:173-8. 作者: StephenW 时间: 2018-10-9 21:29
266
胎儿暴露于替诺福韦的长期安全性
来自乙型肝炎母亲的婴儿
Calvin Q. Pan1，Zhongping Duan2，Er Hei Dai3，Guo-Rong
Han4，Shu Qing Zhang5，Yuming Wang6，Huai Hong Zhang7，
宝申朱8，苏文丽8，洪秀秀4，易鼎4，文
Jing Zhao9，Shi Lian Li10，Xiao Hu Zhang7和Huai Bin Zou2，
（1）纽约消化内科和肝脏病科
大学兰贡健康，（2）北京人工肝中心
佑安医院，（3）石家庄市第五医院，（4）
第二届妇产科
东南大学附属医院，（5）系
吉林市肝胆病医院人工肝
省，（6）西南地区传染病研究所
军医大学医院，（7）医学系，
南阳中心医院，（8）妇产科
石家庄市第五医院产科，（9）中央
吉林省肝胆疾病医院实验室，
（10）西南医院传染病研究所
背景：关于长期影响的随机试验数据
关于婴儿的身体发育和神经发育的使用
替诺福韦地索普西富马酸盐（TDF）治疗慢性乙型肝炎
（CHB）母亲缺乏。方法：所有180名婴儿
完成了IN-US174-0174研究的参与
在长期随访（LTFU）研究中.1他们来自CHB
随机分配（1：1比例）的母亲接受
没有抗病毒治疗的常规护理或接受TDF
妊娠30至32周，直至产后第4周
在LTFU研究中，婴儿在72岁时进行了评估，
120和192周的生长和神经发育
Bayley-III测量。他们的骨密度（BMD）
在第192周测量。神经发育延迟
由认知和语言综合评分定义
<85（低于平均100的1 SD）.2这些参数
在TDF暴露和TDFunexposed之间进行了比较
组。结果：180名婴儿中完成了
在初步研究中，176名（98％）参加了LTFU研究
144人（82％）完成了LTFU。在TDF暴露
组，胎儿暴露于TDF的平均值（±SD）
是8.57±0.53周。孕龄，分娩方式，
出生时的体重，身高和Apgar评分相似
两组。在第192周，没有显着差异
在包括头部在内的组之间的预先指定的结果中
周长，身高，BMD，认知，社交情绪
组之间的适应性行为测量。
该队列中没有神经发育迟缓。在里面
TDF暴露组，儿童的运动复合物明显增多
得分（146.46±6.39 vs 142.88±9.54; p = 0.009）和
男孩的平均体重明显较低（18.48±2.35kg）
vs 19.84±3.46kg; p = 0.029）。然而，男孩的意思是身体
TDF暴露组的体重明显较高
比4岁的全国华人参考值
男生（18.48±2.35kg vs 16.64±1.89; p = 0.010）.3结论：
在胎儿暴露于TDF的婴儿中，身体上
生长，骨密度和神经发育与那些相似
没有暴露，在中国人的正常范围内
在192周的随访期间参考值。我们的数据支持
在母亲的第三个三个月使用TDF的安全性
与CHB。致谢由吉利德科学资助;
ClinicalTrials.gov号，NCT01488526。）参考文献：Pan
CQ，Duan Z，Dai E，et al。替诺福韦预防乙型肝炎
高病毒载量的母亲传播。 N Engl J Med
2016; 374：2324-34。约翰逊S，摩尔T，马洛N.使用
Bayley-III评估神经发育迟缓：哪种截止
应该用吗？ Pediatr Res 2014; 75：670-4。李H. [成长
基于重量，长度的标准化值和曲线/
中国7岁以下儿童的身高和头围
岁]。中华二科杂志2009; 47：173-8。
由吉利德科学资助;