BACKGROUND & AIMS Long-term safety outcome of children with fetal exposure to tenofovir disoproxil fumarate (TDF) to prevent maternal transmission of hepatitis B virus (HBV) is lacking. METHODS Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visit 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 TDF and 57 in 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/1.73mˆ2, P = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in TDF and control group had comparable levels of serum calcium (2.61 ± 0.02 vs. 2.57 ± 0.02 mmol/L, P = 0.115), phosphorus (5.29 ± 0.05 vs. 5.23 ± 0.05 mg/dL, P = 0.379), bone specific alkaline phosphatase (64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L, P = 0.736), calcidiol (33.25 ± 0.70 vs. 32.82 ± 0.80 ng/mL, P = 0.687) and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cmˆ2, P = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cmˆ2, P = 0.926). CONCLUSIONS Children of HBV mothers with and without TDF treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

中文翻译：

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有或没有胎儿接触富马酸替诺福韦二吡呋酯的 HBV 感染母亲的儿童的长期生长和骨骼发育

背景和目的 胎儿暴露于富马酸替诺福韦二吡呋酯 (TDF) 以防止母体传播乙型肝炎病毒 (HBV) 的儿童缺乏长期安全性结果。方法 招募参与妊娠晚期母体 TDF 治疗的前瞻性多中心试验的儿童，每年进行一次随访。通过双能 X 射线吸收仪扫描测量生长参数、血清生化、HBV 血清学和骨矿物质密度 (BMD)。结果 128 名儿童（TDF 71 名和对照组 57 名）在 2 至 7 岁（中位数，4.08）岁时完成了 255 次随访。年龄别体重的 z 分数没有差异（0.26 ± 0.90 对 0.22 ± 0.99，P = 0.481），年龄别身高的 z 分数（0.20 ± 1.02 对 0.25 ± 0.98，P = 0.812） , 和估计的肾小球滤过率 (169.12 ± 50. 检测到 48 与 169.06 ± 34.46 毫升/分钟/1.73m^2，P = 0.479)。通过多元线性回归调整年龄、性别和 HBV 状态后，TDF 和对照组儿童的血清钙水平（2.61 ± 0.02 vs. 2.57 ± 0.02 mmol/L，P = 0.115）、磷（5.29 ± 0.05 vs. . 5.23 ± 0.05 mg/dL, P = 0.379), 骨特异性碱性磷酸酶 (64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L, P = 0.736), 骨化二醇 (33.25 ± 0.70, P ±32 mL, P = 0.687) 和腰椎的 BMD (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm^2, P = 0.159) 和左髋 (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm^2, P = 0.926)。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。通过多元线性回归调整年龄、性别和 HBV 状态后，TDF 和对照组儿童的血清钙水平（2.61 ± 0.02 vs. 2.57 ± 0.02 mmol/L，P = 0.115）、磷（5.29 ± 0.05 vs. . 5.23 ± 0.05 mg/dL, P = 0.379), 骨特异性碱性磷酸酶 (64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L, P = 0.736), 骨化二醇 (33.25 ± 0.70, P ±32 mL, P = 0.687) 和腰椎的 BMD (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm^2, P = 0.159) 和左髋 (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm^2, P = 0.926)。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。通过多元线性回归调整年龄、性别和 HBV 状态后，TDF 和对照组儿童的血清钙水平（2.61 ± 0.02 vs. 2.57 ± 0.02 mmol/L，P = 0.115）、磷（5.29 ± 0.05 vs. . 5.23 ± 0.05 mg/dL, P = 0.379), 骨特异性碱性磷酸酶 (64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L, P = 0.736), 骨化二醇 (33.25 ± 0.70, P ±32 mL, P = 0.687) 和腰椎的 BMD (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm^2, P = 0.159) 和左髋 (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm^2, P = 0.926)。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。TDF 和对照组儿童的血清钙水平相当（2.61 ± 0.02 对 2.57 ± 0.02 mmol/L，P = 0.115）、磷（5.29 ± 0.05 对 5.23 ± 0.05 mg/dL，P = 0.379）、骨特异性碱性磷酸酶（64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L，P = 0.736）、骨化二醇（33.25 ± 0.70 vs. 32.82 ± 0.80 ng/mL，P = 0.687）和 BMD（0.5 s.0 流明的脊椎骨密度） 0.57 ± 0.01 g/cm^2，P = 0.159) 和左臀部（0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm^2，P = 0.926）。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。TDF 和对照组儿童的血清钙水平相当（2.61 ± 0.02 对 2.57 ± 0.02 mmol/L，P = 0.115）、磷（5.29 ± 0.05 对 5.23 ± 0.05 mg/dL，P = 0.379）、骨特异性碱性磷酸酶（64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L，P = 0.736）、骨化二醇（33.25 ± 0.70 vs. 32.82 ± 0.80 ng/mL，P = 0.687）和 BMD（0.5 s.0 流明的脊椎骨密度） 0.57 ± 0.01 g/cm^2，P = 0.159) 和左臀部（0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm^2，P = 0.926）。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。骨化醇（33.25 ± 0.70 对 32.82 ± 0.80 ng/mL，P = 0.687）和腰椎的 BMD（0.55 ± 0.01 对 0.57 ± 0.01 g/cm^2，P = 0.159）和左髋骨（0.55 ± 0.01 对± 0.01 g/cm^2，P = 0.926)。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。骨化醇（33.25 ± 0.70 对 32.82 ± 0.80 ng/mL，P = 0.687）和腰椎的 BMD（0.55 ± 0.01 对 0.57 ± 0.01 g/cm^2，P = 0.159）和左髋骨（0.55 ± 0.01 对± 0.01 g/cm^2，P = 0.926)。结论 妊娠晚期接受和未接受 TDF 治疗的 HBV 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。