Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
PLoS One. 2012 Dec 20;7(12):e51734. doi: 10.1371/journal.pone.0051734. Epub 2012 Dec 10.
To evaluate the risk of foetal loss associated with pandemic influenza vaccination in pregnancy. Retrospective cohort study. UK General Practice Research Database Pregnancies ending in delivery or spontaneous foetal death after 21 October 2009 and starting before 01 January 2010.
METHODOLOGY/PRINCIPAL FINDINGS: Hazard ratios of foetal death for vaccinated compared to unvaccinated pregnancies were estimated for gestational weeks 9 to 12, 13 to 24 and 25 to 43 using discrete-time survival analysis. Separate models were specified to evaluate whether the potential effect of vaccination on foetal loss might be transient (for ~4 weeks post vaccination only) or more permanent (for the duration of the pregnancy). 39,863 pregnancies meeting our inclusion criteria contributed a total of 969,322 gestational weeks during the study period. 9,445 of the women were vaccinated before or during pregnancy. When the potential effect of vaccination was assumed to be transient, the hazard of foetal death during gestational weeks 9 through 12 (HR(unadj) 0.56; CI(95) 0.43 to 0.73) and 13 through 24 (HR(unadj) 0.45; CI(95) 0.28 to 0.73) was lower in the 4 weeks after vaccination than in other weeks. Where the more permanent exposure definition was specified, vaccinated pregnancies also had a lower hazard of foetal loss than unvaccinated pregnancies in gestational weeks 9 through 12 (HR(unadj) 0.74; CI(95) 0.62 to 0.88) and 13 through 24 (HR(unadj) 0.59; CI(95) 0.45 to 0.77). There was no difference in the hazard of foetal loss during weeks 25 to 43 in either model. Sensitivity analyses suggest the strong protective associations observed may be due in part to unmeasured confounding.
CONCLUSIONS/SIGNIFICANCE: Influenza vaccination during pregnancy does not appear to increase the risk of foetal death. This study therefore supports the continued recommendation of influenza vaccination of pregnant women.
评估大流行流感疫苗接种在妊娠期间与胎儿丢失相关的风险。回顾性队列研究。英国普通实践研究数据库 2009 年 10 月 21 日至 2010 年 1 月 1 日之间结束分娩或自然胎儿死亡的妊娠，并于之前开始。
方法/主要发现：使用离散时间生存分析估计接种疫苗与未接种疫苗的妊娠相比，妊娠 9 至 12 周、13 至 24 周和 25 至 43 周时胎儿死亡的危险比。指定了单独的模型来评估疫苗接种对胎儿丢失的潜在影响是否可能是短暂的（仅在接种疫苗后 4 周内）或更持久的（在整个妊娠期间）。符合我们纳入标准的 39863 例妊娠共贡献了研究期间总共 969322 个妊娠周。在妊娠期间或之前，有 9445 名妇女接种了疫苗。当假设疫苗接种的潜在影响是短暂的时，在接种疫苗后 9 至 12 周（未调整 HR(unadj)0.56；CI(95)0.43 至 0.73）和 13 至 24 周（未调整 HR(unadj)0.45；CI(95)0.28 至 0.73）期间，胎儿死亡的风险较低。在指定更持久的暴露定义的情况下，与未接种疫苗的妊娠相比，接种疫苗的妊娠在妊娠 9 至 12 周（未调整 HR(unadj)0.74；CI(95)0.62 至 0.88）和 13 至 24 周（未调整 HR(unadj)0.59；CI(95)0.45 至 0.77）期间也具有较低的胎儿丢失风险。在这两个模型中，在 25 至 43 周期间，胎儿丢失的风险没有差异。敏感性分析表明，观察到的强烈保护关联可能部分归因于无法测量的混杂因素。
结论/意义：妊娠期间流感疫苗接种似乎不会增加胎儿死亡的风险。因此，这项研究支持继续建议孕妇接种流感疫苗。
