富氟替诺福韦酯对胎儿的HBV感染母亲的儿童长期生长和骨骼

StephenW

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate

    Wan-Hsin Wen
    Huey-Ling Chen
    Tiffany Ting-Fang Shih
    Hong-Yuan Hsu
    Mei-Hwei Chang
    theTaiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT study)‡
    Show all authors

Published:February 07, 2020DOI:https://doi.org/10.1016/j.jhep.2020.01.021
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Highlights

    •
    Short-term TDF use during pregnancy to prevent maternal HBV transmission is safe.
    •
    Children with and without fetal exposure to TDF have comparable long-term growth.
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    Children's renal function and bone development are unaffected.

Background & Aims
Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF.
Methods
Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured.
Results
One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926).
Conclusions
Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6–7 years after delivery.
Clinical trial number
NCT01312012 (ClinicalTrials.gov)
Lay summary
Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

StephenW

富氟替诺福韦酯对胎儿的HBV感染母亲的儿童长期生长和骨骼发育

    温万新
    陈慧玲
    蒂芬妮·施芳芳
    徐宏远
    张美慧
    台湾预防HBV母婴传播研究小组（PreMIT研究）‡
    显示所有作者

发布时间：2020年2月7日DOI：https：//doi.org/10.1016/j.jhep.2020.01.021
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强调

    •
    怀孕期间短期使用TDF预防孕妇HBV传播是安全的。
    •
    有和没有胎儿暴露于TDF的儿童具有相当的长期生长。
    •
    儿童的肾功能和骨骼发育不受影响。

背景与目标
由于其有效性和安全性，替诺福韦酯富马酸替索罗非酯（TDF）是预防孕妇传播HBV的首选治疗方法。但是，缺乏胎儿暴露于TDF后儿童的长期安全性结果的数据。
方法
招募参加妊娠晚期母体TDF治疗的前瞻性，多地点试验的儿童，每年进行一次随访。通过双能X线骨密度仪测量生长参数，血清生化，HBV血清学和骨矿物质密度（BMD）。
结果
一百二十八名儿童，其中在TDF中为71名，在对照组中为57名，在2至7岁（中位数为4.08）岁时完成了255次随访。年龄别体重的z得分无差异（0.26±0.90 vs.0.22±0.99，p = 0.481），年龄别体重的z得分（0.20±1.02 vs. 0.25±0.98，p = 0.812） ，并检测出估计的肾小球滤过率（169.12±50.48与169.06±34.46 ml / min / 1.73m2，p = 0.479）。通过多元线性回归调整年龄，性别和HBV状况后，TDF组和对照组儿童的腰椎血清钙，磷，骨特异性碱性磷酸酶，骨化二醇和BMD水平相当（0.55±0.01 vs. 0.57± 0.01 g / cm2，p = 0.159）和左臀部（0.56±0.01 vs. 0.56±0.01 g / cm2，p = 0.926）。
结论
在怀孕晚期期间接受或未接受替诺福韦富马酸替诺福韦酯治疗的被HBV感染的母亲的孩子在分娩后6-7年内具有相当的长期生长，肾功能和骨骼发育。
临床试验编号
NCT01312012（ClinicalTrials.gov）
放置摘要
目前，对于在怀孕期间服用抗病毒药以防止母婴传播乙型肝炎病毒（HBV）的母亲所生的孩子，缺乏长期的安全性数据。在这项研究中，我们发现在怀孕后期接受或未接受替诺福韦富马酸替诺福韦酯治疗的HBV感染母亲的孩子在分娩后6-7年内具有相当的长期生长，肾功能和骨骼发育。

StephenW

https://www.journal-of-hepatolog ... 8278(20)30062-3/pdf