To systematically evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) treatment during the second or third trimester of pregnancy for preventing mother-to-infant transmission of hepatitis B virus (HBV).

Randomized controlled trials (RCTs) and cohort studies on efficacy and safety of TDF in the second and third trimester of pregnancy for the prevention of mother-to- infant transmission of HBV were collected by searching related databases at home and abroad (up to July 20, 2019). Quality of RCTs and cohort studies were evaluated using bias risk assessment tool of Cochrane collaboration networks and Newcastle-Ottawa Scale, respectively. Meta-analysis was performed using RevMan 5.3 software. The continuous data were expressed using standardized mean difference (SMD) and its 95% confidence interval (CI). The effect values of meta-analysis of dichotomous variables were expressed using odds ratio (OR) and its 95%CI for effectiveness outcome or risk ratio (RR) and 95%CI for safety outcome.

A total of 12 studies (2 RCTs and 10 cohort studies) were entered, including 1 326 HBV-infected mothers and their 1 281 infants, of which 729 mothers took TDF (the TDF group) and 597 mothers were without intervention or took placebo (the control group) in the second or third trimester of pregnancy. The results of quality evaluation showed that one of the 2 RCTs was at low risk of bias and the other one was at high risk of bias; 9 of the 10 cohort studies were of high quality and one was of medium quality. The meta analysis for effectiveness outcomes showed that the baseline HBV DNA level in patients in the TDF group was significantly higher than that in the control group (SMD=0.15, 95%CI: 0.04-0.26, P=0.008), the prenatal HBV DNA level in patients in the TDF group was significantly lower than that in the control group (SMD=-5.41, 95%CI: -7.26--3.56, P<0.001), the proportion of mothers with HBV DNA undetected before delivery in the TDF group was significantly higher than that in the control group [20.3% (41/202) vs. 2.0% (4/203), OR=27.55, 95%CI: 7.32-103.85, P<0.001], and the HBV infection rate of infants born to mothers in the TDF group was significantly lower than that in the control group [0.8% (5/618) vs. 9.1% (47/516), RR=0.13, 95%CI: 0.07-0.27, P<0.001]. The meta analysis for safety outcomes showed that the differences in the incidence of birth defects, mortality, birth weight, height and head circumference between the TDF group and the control group were not statistically significant (P>0.05 for all), the difference in the incidence of postpartum alanine aminotransferase level rise between the TDF group and the control group was not statistically significant (P>0.05); the results of one study showed that the proportion of mothers with grade 1-2 asymptomatic creatine kinase increase in the TDF group was higher than that in the control group [7.2% (7/97) vs. 0 (0/100), P=0.006] and the differences in the incidence of other adverse pregnancy events and complications in the 2 groups were not statistically significant (P>0.05 for all).

The treatment of TDF in the second and third trimester of pregnancy can effectively prevent mother-to-infant transmission of HBV and has no significant impact on growth and development of the fetus.

Tenofovir; Hepatitis B; Pregnancy; Infectious disease transmission, vertical; Maternal exposure; Safety; Meta-analysis