Fabiani Massimo, Bella Antonino, Rota Maria C, Clagnan Elena, Gallo Tolinda, D'Amato Maurizio, Pezzotti Patrizio, Ferrara Lorenza, Demicheli Vittorio, Martinelli Domenico, Prato Rosa, Rizzo Caterina
National Centre for Epidemiology, Surveillance and Health Promotion, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
Epidemiological Unit, Regional Central Directorate for Health, Social-Health Integration, Social Policy, and Family, Udine, Italy.
Vaccine. 2015 May 5;33(19):2240-2247. doi: 10.1016/j.vaccine.2015.03.041. Epub 2015 Mar 26.
Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during pregnancy but, because of the reduced statistical power, meta-analyses and large multi-centres studies are needed in order to obtain more conclusive results, especially for rare outcomes.
尽管过去曾有人对孕期接种流感疫苗的安全性提出担忧，但在2009年甲型H1N1流感大流行期间，许多国家都建议孕妇接种疫苗。开展了一项回顾性队列研究，以评估接种含MF59佐剂的甲型H1N1流感大流行疫苗的孕妇出现不良母体、胎儿和新生儿结局的风险。该研究在意大利四个地区（皮埃蒙特、弗留利-威尼斯朱利亚、拉齐奥和普利亚）进行，研究对象为102,077名在2009/2010年实施的疫苗接种活动中，在妊娠中期或晚期可能接触过疫苗的孕妇。基于从地区行政数据库检索到的数据，采用Cox比例风险模型进行统计分析，并对倾向得分进行调整，以考虑由于社会人口特征以及女性的临床和生殖史导致的潜在混杂效应。共有100,332名孕妇符合分析条件。其中，2003名（2.0%）孕妇在妊娠中期或晚期接种了甲型H1N1流感大流行疫苗。我们未观察到甲型H1N1流感大流行疫苗接种与不同的母体结局（因流感、肺炎、高血压、子痫、糖尿病、甲状腺疾病和贫血住院）、胎儿结局（妊娠22周后胎儿死亡）和新生儿结局（早产、低出生体重、5分钟阿氏评分低和先天性畸形）之间存在任何统计学上的显著关联。在接种疫苗的女性中，孕前存在健康风险状况（妊娠开始前因特定疾病住院和开具药物处方）的情况更为常见，因此表明合并慢性病会增加疫苗接种率。本研究结果为孕期接种甲型H1N1流感大流行疫苗的安全性提供了一些证据，但由于统计效力降低，需要进行荟萃分析和大型多中心研究以获得更确凿的结果，尤其是针对罕见结局。
