BACKGROUND Epidemic forms of hepatitis E cause high mortality among pregnant people, with case fatality risks over 30% and adverse fetal outcomes. In 2022, the first mass reactive vaccination campaign against hepatitis E was conducted in South Sudan with the HEV239 vaccine. We aimed to assess whether vaccination against hepatitis E in pregnancy increases the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant people. METHODS In this emulated target trial, an exhaustive pregnancy census was conducted in Bentiu internally displaced persons camp after the second of three vaccination rounds. Women and girls aged 14-45 years with no current jaundice or acute illness were eligible for participation. Individuals who consented were revisited 28 days after their delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched vaccinated to unvaccinated participants on age, gestational age, and vaccination propensity score and estimated cumulative incidence functions for fetal loss in vaccinated compared to unvaccinated women in a competing risks framework using the Aalen-Johansen estimator. FINDINGS Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9). INTERPRETATION No evidence of increased risk of fetal loss was found among individuals vaccinated during pregnancy. FUNDING Médecins Sans Frontières.

中文翻译：

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戊型肝炎疫苗在妊娠期的安全性：在南苏丹班提乌国内流离失所者营地开展大规模反应性疫苗接种运动后的模拟靶向试验。


背景 戊型肝炎的流行形式导致孕妇死亡率高，病死风险超过 30% 和不良胎儿结局。2022 年，南苏丹使用 HEV239 疫苗开展了第一次针对戊型肝炎的大规模反应性疫苗接种运动。我们旨在评估妊娠期接种戊型肝炎疫苗是否会增加接种疫苗和未接种疫苗的孕妇队列的胎儿丢失风险。方法 在这项模拟目标试验中，在三轮疫苗接种中的第二轮之后，在 Bentiu 国内流离失所者营地进行了详尽的妊娠普查。年龄在 14-45 岁之间且目前没有黄疸或急性疾病的妇女和女孩有资格参加。同意的个体在分娩日期后 28 天重新访视，以记录妊娠结局。我们使用模拟的靶向试验框架来解决观察性研究中固有的偏倚。我们使用 Aalen-Johansen 估计器在竞争风险框架中，将接种疫苗的参与者与未接种疫苗的参与者的年龄、胎龄和疫苗接种倾向评分以及估计的胎儿丢失累积发生率函数进行匹配。结果在 2022 年 5 月 16 日至 6 月 30 日期间，招募了 3421 名参与者并进行了随访以纳入分析。在疫苗接种活动开始后有妊娠结局的 2741 名妇女中，67 名 （2·4%） 在受孕前接种了疫苗，2036 名 （74·3%） 在怀孕期间接种了疫苗，638 名 （23·2%） 未接种疫苗。 在匹配分析中保留的 2407 名妇女中，怀孕期间接种疫苗的个体的累积流产风险为 7·2% （95% CI 5·6-8·7），而未接种疫苗的个体为 6·1% （3·7-9·2），这意味着风险比为 1·2 （95% CI 0·7-1·9）。解释 在怀孕期间接种疫苗的个体中没有发现胎儿丢失风险增加的证据。资助 无国界医生组织.