(围)妊娠期HPV疫苗接种对后代出生缺陷发生风险的影响

Birth defects after human papilloma virus vaccination in periconceptional period or during pregnancy

目的评估(围)妊娠期人乳头瘤病毒(human papilloma virus,HPV)疫苗接种对后代出生缺陷发生风险的影响。方法通过检索PubMed数据库、Cochrane Library数据库、中国知网数据库和万方数据库,系统性收集(围)妊娠期HPV疫苗接种对后代出生缺陷发生风险影响研究,检索时间均从建库至2019年10月31日。根据纳入及排除标准,由2名系统评价员独立地进行文献筛选及数据提取,应用Review Manager 5.3软件进行荟萃分析。结果6项研究报告了(围)妊娠期四价HPV疫苗接种与后代出生缺陷发生风险间的关联。荟萃分析结果显示,妊娠前45天至妊娠结束期间接种四价HPV疫苗并未增加出生缺陷发生风险(RR=0.94,95%CI:0.60-1.48);妊娠前45天至末次月经(last menstrual period,LMP)期间接种四价HPV疫苗增加出生缺陷发生风险(RR=1.34,95%CI:1.01-1.78);妊娠期间接种四价HPV疫苗并未增加出生缺陷发生风险(RR=1.18,95%CI:0.92-1.51)。一项研究报告了(围)妊娠期二价HPV疫苗接种与后代出生缺陷发生风险间的关联。结果显示妊娠前45天至妊娠结束期间接种二价HPV疫苗并未增加出生缺陷发生风险(RR=0.93,95%CI:0.49-1.75)。结论(围)妊娠期二价/四价HPV疫苗暴露不显著增加后代出生缺陷发生风险。

Objective To assess whether inadvertent human papilloma virus(HPV)vaccine exposures in the periconceptional period or during pregnancy were associated with increased risks for birth defects.Methods A search of PubMed,Cochrane Library,China National Knowledge Infrastructure(CNKI),and Wan Fang databases(until October 31,2019)was performed.Studies that assess the risk of birth defects in HPV vaccine exposed/unexposed pregnancies were included.The pooled relative risk(RR)was applied for the effect measure of the study.RRs and 95%confidence interval(CI)were measured when the paper did not report the effect.Heterogeneity between studies was assessed using the Cochrane’s Q and I 2 statistics.Results Six studies were eligible and all studies were low risk of bias.Meta-analyses suggested that 4vHPV vaccination did not increase the risk of birth defects regardless of exposure period during 45 days before last menstrual period or pregnancy:RR=0.94,95%CI:0.60-1.48,or during pregnancy:RR=1.18,95%CI:0.92-1.51.However,vaccination during Pre-45 days to LMP seemed to increase the risk of birth defects:RR=1.34,95%CI:1.01-1.78.In addition,it is suggested that 2vHPV vaccination did not increase the risk of birth defects when exposure period during 45 days before last menstrual period or pregnancy:RR=0.93,95%CI:0.49-1.75.Conclusion Inadvertent bivalent/quadrivalent HPV vaccination during pregnancy was not associated with significantly greater risks of birth defects.