Safety of hepatitis E vaccination for pregnancy: a post-hoc analysis of a randomized, double-blind, controlled phase 3 clinical trial

Abstract

Special attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18-45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38-1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74-8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

Keywords: Hecolin; Hepatitis E vaccine; human papillomavirus vaccine; pregnancy; safety.

Figure 1.

Study profile. HE: Hepatitis E. HPV: Human papillomavirus. All the women who received at least one dose of vaccine were followed up to 66 months. *By mistake, one participant in the HPV vaccine group was given the HE vaccine for dose 1, and two participants in the HE vaccine group were given the HPV vaccine for dose 3. These three participants were included in the HPV vaccine group for safety analysis, according to the protocol. ^†One woman with one pregnancy event in the HPV vaccine group was excluded from the analysis due to loss of follow-up and incomplete information on pregnancy outcome. ^‡Proximal exposure was defined as vaccination during pregnancy or the onset of pregnancy within 90 days post any dose. Abbreviations: HE, hepatitis E; HPV, human papillomavirus.