Norwegian Institute of Public Health, Oslo, Norway.
N Engl J Med. 2013 Jan 24;368(4):333-40. doi: 10.1056/NEJMoa1207210. Epub 2013 Jan 16.
During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination.
We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables.
There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17).
Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).
在 2009 年甲型 H1N1 流感大流行期间，孕妇面临罹患严重流感的风险。由于有传闻称孕妇接种疫苗后发生胎儿死亡，因此人们对孕妇接种疫苗的安全性产生了担忧，这使上述情况变得更为复杂。
我们通过将挪威全国性注册中心和医疗咨询数据相链接，来探究孕妇接种流感疫苗的安全性，以确定流感诊断、疫苗接种情况、妊娠结局以及大流行前后孕妇的背景信息。我们使用 Cox 回归模型来估计胎儿死亡的风险比，以妊娠天数为时间指标，并将疫苗接种和大流行暴露作为时间依赖性暴露变量。
在 2009 年至 2010 年期间，挪威有 117347 例符合条件的妊娠。胎儿死亡率为每 1000 例活产 4.9 例死亡。在大流行期间，有 54%处于第二或第三孕期的孕妇接种了疫苗。孕期接种疫苗可显著降低流感诊断的风险（调整后的风险比为 0.30；95%置信区间为 0.25 至 0.34）。对于有临床诊断流感的孕妇，胎儿死亡的风险增加（调整后的风险比为 1.91；95%置信区间为 1.07 至 3.41）。虽然孕期接种疫苗降低胎儿死亡风险的效果并不显著（调整后的风险比为 0.88；95%置信区间为 0.66 至 1.17），但确实降低了这种风险。
妊娠期间感染大流行流感病毒与胎儿死亡风险增加相关。孕期接种疫苗可降低流感诊断的风险。接种疫苗本身与胎儿死亡风险增加无关，而且可能降低了大流行期间与流感相关的胎儿死亡风险。（由挪威公共卫生研究所资助）。
