McMillan M, Porritt K, Kralik D, Costi L, Marshall H
School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide 5005, SA, Australia.
Joanna Briggs Institute, Faculty of Health Sciences, The University of Adelaide, Adelaide 5005, SA, Australia.
Vaccine. 2015 Apr 27;33(18):2108-17. doi: 10.1016/j.vaccine.2015.02.068. Epub 2015 Mar 8.
Pregnant women are considered the most important risk group for influenza vaccination. Despite this, the potential risk of harm from the vaccine on the fetus is a key factor in low uptake of the vaccine. This systematic review aimed to synthesize the best available evidence on the safety of influenza vaccination during pregnancy on fetal development.
A search of the literature was undertaken from the inception of each database up to March 2014. Both observational and clinical trials were considered. Fetal outcomes were present in 19 observational studies, and 14 of those were primarily investigating the monovalent influenza A (H1N1) 2009 vaccine. There was significant methodological and clinical heterogeneity of the included studies and a narrative summary and tabling of results was performed. Fetal death outcomes for women in later pregnancy ranged from OR 0.34 to 2.95 with 95% confidence intervals crossing or below the null value. Spontaneous abortion less than 24 weeks ranged from HR 0.45 to OR 1.23, with 95% confidence intervals crossing or below the null value. Congenital malformations for women vaccinated during their first trimester ranged from OR 0.67 to 2.18 and imprecise confidence intervals crossed the null value. Included in this review were some high quality studies, although overall the studies have a high risk of selection and confounding bias.
Results do not indicate that maternal influenza vaccination is associated with an increased risk of fetal death, spontaneous abortion, or congenital malformations. Statistical imprecision and clinical and methodological heterogeneity of the observational studies mean it is not possible to totally exclude adverse effects. Further studies investigating women vaccinated during their first trimester should be the highest priority to allow for more precise estimates, especially for spontaneous abortion, and congenital abnormality outcomes.
孕妇被认为是流感疫苗接种的最重要风险群体。尽管如此，疫苗对胎儿潜在的危害风险是疫苗接种率低的关键因素。本系统评价旨在综合关于孕期接种流感疫苗对胎儿发育安全性的现有最佳证据。
检索了各数据库自创建至2014年3月的文献。纳入观察性研究和临床试验。19项观察性研究中有胎儿结局相关内容，其中14项主要研究2009年甲型H1N1单价流感疫苗。纳入研究存在显著的方法学和临床异质性，因此进行了结果的叙述性总结和列表。孕晚期妇女的胎儿死亡结局的比值比（OR）范围为0.34至2.95，95%置信区间跨越或低于无效值。妊娠24周前的自然流产的风险比（HR）范围为0.45至OR 1.23，95%置信区间跨越或低于无效值。孕早期接种疫苗的妇女的先天性畸形的OR范围为0.67至2.18，不精确的置信区间跨越无效值。本综述纳入了一些高质量研究，尽管总体而言这些研究存在较高的选择和混杂偏倚风险。
结果未表明孕妇接种流感疫苗会增加胎儿死亡、自然流产或先天性畸形的风险。观察性研究的统计不精确性以及临床和方法学异质性意味着无法完全排除不良反应。应优先开展进一步研究，调查孕早期接种疫苗的妇女，以便进行更精确的评估，尤其是针对自然流产和先天性异常结局。
