Discussion
abnormal foetal loss
PREGNANCY COMPLICATION, HPV INFECTION, INFECTIONS TOE, EVENTS, INFECTION TOE
This post-hoc analysis showed that the HE vaccine did not have a negative effect on pregnancy relative to risks observed in HPV-vaccinated subjects. The incidences of adverse pregnancy outcomes were low and comparable between the HE vaccine receivers and HPV vaccine receivers. No potential risk was observed in vaccinated women of both the advanced or non-advanced maternal age. Additionally, there was no increased risk of abnormal foetal loss, neonatal abnormality, and pregnancy complication in women who received the HE vaccine during pregnancy or within 90 days pre-pregnancy compared with those who became pregnant at more than 90 days after vaccination. The vaccine was well tolerated during pregnancy and no vaccine-related SAE was reported.Since licensure in 2006, over 500 million doses of HPV vaccines have been distributed and 126 countries have introduced the HPV vaccine into their national immunization programmes [A large proportion of terminations were caused by elective terminations in our study, which may be closely associated with China’s birth control policy. During the first year of our study, only couples who were both from one-child families were allowed to have two children. Since November 2013, a selective two-child policy was available if either spouse was an only child, and a universal two-child policy was implemented by Chinese government after 2016 [There is increasing momentum to develop and implement maternal immunization to prevent specific infections to which pregnancy and newborns are susceptible. Theoretically, it is safe to receive an inactivated vaccine during pregnancy, whereas live vaccines should be contraindicated owing to the potential risk of infection to the foetus [As the only one commercialized HE vaccine around the world, Hecolin is of high priority for susceptible populations, including women of child-bearing age, and vaccinating women of child-bearing age has been indicated to be cost-effective from the societal perspective especially in epidemic regions [This post-hoc analysis was accompanied by a number of limitations. Firstly, the long-term effects of the vaccine on infants could not be analysed because the pregnancy events were followed only up to one month after delivery. Another limitation was the small number of women vaccinated during pregnancy. It is challenging to observe rare vaccine-related adverse outcomes based on such a limited sample size. A randomized, controlled clinical trial designed specifically for pregnant women would be the “golden rule” to rule out a meaningful difference in the percentage of adverse pregnancy outcomes. In addition, this phase 3 clinical trial was designed to evaluate the efficacy against HPV infection, therefore the antibody response specific to HEV after vaccination during pregnancy was not assessed and remained to be investigated.In conclusion, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes, but caution is needed until more adequate evidence is available. These data may be helpful to guide clinical practice in reducing undue concerns about the safety of vaccination during or shortly before pregnancy.