Abstract: Objective To study hepatitis B virus (HBV) mother-to-child transmission and the impact factors, providing the basis for preventive strategies. Methods A total of 154 hepatitis B surface antigen (HBsAg)-positive pregnant women and 297 HBsAg-negative pregnant women from Baoshan District Centers for Disease Control and Prevention in Shanghai were enrolled and received an epidemiological survey regarding mother-to-child transmission. Mothers' peripheral blood and newborns' cord blood were collected to be tested for HBV serological markers and HBV DNA load. HBsAg positivity and HBV DNA ≥ 10³ copies/mL in cord blood of newborns born of HBsAg-positive mothers was defined as trans-placental HBV transmission. Results The trans-placental transmission rate was found to be 8.4% for HBsAg-positive mothers. Trans-placental transmission rate was significantly higher among both HBsAg and HBeAg-positive women compared to those only with HBsAg-positiveness (20.0% vs. 3.7%, relative risk was 5.41, P<0.05), and increased with HBV DNA load in mothers' peripheral blood. Conclusion HBeAg can directly transmit through the placenta, while HBsAg is "filtered" to a certain degree. HBeAg positiveness and high HBV DNA load of the mother are risk factors in trans-placental transmission, and possibly lead to the failure of newborn immunoprophylaxis.