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

Abstract 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.