追加：第 27 节第 18 条，怀孕期间赶上流感季就打一针流感灭活疫苗

2026-10-14 追加。四问：孕妇是流感重症的高危人群，读者普遍碰得上；国内有的疫苗说明书过去把孕妇列为禁忌，很多人以为孕期不能打；全书原有的流感疫苗条目只有第 1 节第 20 条（心血管病人和老年人），没写孕妇和 6 月龄以下婴儿；来源是随机试验、汇总分析、WHO 立场文件和中国疾控中心年度指南原文。

全书查重：grep -n 流感 book/*.md，孕妇接种在全书没有出现过。第 20 节新生儿那几条只写国家免疫规划疫苗，流感疫苗不在免疫规划里，不重复。

1. WHO 立场文件（2022 年 5 月）

  • 题录：Vaccines against influenza: WHO position paper – May 2022. Weekly Epidemiological Record, No 19, 2022, 97, 185–208。PDF 经 iris.who.int 的 DSpace 接口取得（/server/api/core/bitstreams/search/byItemHandle?handle=10665/354264&filename=WER9719-eng-fre.pdf 给出 content 链接），pdftotext 逐字抽出。iris 的 bitstream/handle 旧链接只返回前端壳页。
  • 孕妇住院风险：「A systematic review14 in 2017 and a meta-analysis15 in 2019 showed that influenza during pregnancy resulted in a 7 times higher risk of hospital admission (OR 6.8, 95% CI 6–7.7) but a lower risk of admission to ICU (OR 0.6, 95% CI 0.5–0.7); it was not significantly associated with an increased risk of death (OR 1, 95% CI 0.8–1.3) compared with non-pregnant individuals.」
    • 注意：同一句说孕妇得流感死亡风险并不显著更高。所以条目只写住院，不写「孕妇得流感更容易死」。中国疾控指南写的「死亡（OR=3.62）」和 WHO 这里的死胎 RR 3.62 数字相同、出处不同，没核到原文，不采用。
  • 推荐：「Influenza vaccines are safe and effective in preventing infection in pregnant individuals, complications during the pregnancy and influenza infection in the baby in its first few months of life. Any of the currently available inactivated or recombinant seasonal influenza vaccines authorized as age-appropriate may be used, since there are demonstrated benefits over no vaccination.」
  • 任何阶段：「Vaccination may be administered at any stage of pregnancy, preferably prior to the start of the influenza season. The risk of influenza infection to the mother, and thus to the fetus, is higher than that associated with the inactivated influenza vaccine, which has a wellestablished safety record.」
  • 减毒活疫苗：「Because LAIV is a live-virus vaccine and data on its administration to pregnant women and the associated maternal and fetal risks are limited, LAIV is also not recommended during pregnancy.」
  • 安全史：「IIVs have been administered to pregnant women for the past 50 years. Clinical trials and observational studies in pregnant women, including studies that have looked at fetal death, spontaneous abortion and congenital malformations, have found no evidence of any IIVassociated adverse effects in either the women or their newborn babies.」

2. Zaman 2008，孟加拉随机试验

  • 题录：Zaman K 等 (2008). NEJM 359(15):1555-1564. https://doi.org/10.1056/NEJMoa0708630（PMID 18799552），摘要经 Europe PMC REST 取得。
  • 摘要原文：「In this randomized study, we assigned 340 mothers to receive either inactivated influenza vaccine (influenza-vaccine group) or the 23-valent pneumococcal polysaccharide vaccine (control group). Mothers were interviewed weekly to assess illnesses until 24 weeks after birth.」
  • 「Among infants of mothers who received influenza vaccine, there were fewer cases of laboratory-confirmed influenza than among infants in the control group (6 cases and 16 cases, respectively), with a vaccine effectiveness of 63% (95% confidence interval [CI], 5 to 85).」
  • 「Among the mothers, there was a reduction in the rate of respiratory illness with fever of 36% (95% CI, 4 to 57).」
  • 6 月龄以下不能打：「Inactivated influenza vaccine is recommended for pregnant women but is not licensed for infants younger than 6 months of age.」

3. Madhi 2014，南非随机试验

  • 题录：Madhi SA 等 (2014). NEJM 371(10):918-931. https://doi.org/10.1056/NEJMoa1401480（PMID 25184864）。同题还有 2014 年的读者来信（10.1056/NEJMc1412050），不是这篇。
  • 「We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa」
  • 「The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4).」

4. 婴儿的汇总：Nunes 2018、Jarvis 2020

  • Nunes MC, Madhi SA (2018). Hum Vaccin Immunother 14(3):758-766. https://doi.org/10.1080/21645515.2017.1345385（PMID 28708952）。中国疾控 2025—2026、2026—2027 两版指南都引了它。
    • 「Four randomized control trials and 3 observational studies reported on the prevention of laboratory-confirmed influenza infection in infants <6 months old. Maternal influenza vaccination was associated with a 48% [95% confidence interval (CI): 33 to 59] reduced risk of infants having laboratory-confirmed influenza infection. Four observational studies reported on the prevention of hospitalizations associated with laboratory-confirmed influenza infection and the pool estimate was 72% (95%CI: 39% to 87%).」
  • Jarvis JR 等 (2020). Vaccine 38(7):1601-1613. https://doi.org/10.1016/j.vaccine.2019.12.056（PMID 31932138）。
    • 「In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15-50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old.」
    • 条目把这篇的「流感样病没有差别」写进了收益栏，免得只报好的一面。

5. 孕妇住院：Thompson 2019

  • 题录：Thompson MG 等 (2019). Clin Infect Dis 68(9):1444-1453. https://doi.org/10.1093/cid/ciy737（PMID 30307490）。
  • 「The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems … in Australia, Canada (Alberta and Ontario), Israel, and the United States」；「pregnancies overlapped with local influenza seasons from 2010 through 2016」
  • 「the adjusted overall IVE was 40% (95% confidence interval = 12%-59%) against influenza-associated hospitalization during pregnancy.」
  • 中国疾控 2026—2027 指南同样写「对住院的 VE 为 40%（95%CI: 12%—59%）[79]」，引的就是这篇。

6. 安全性

  • Giles ML 等 (2019). Hum Vaccin Immunother 15(3):687-699. https://doi.org/10.1080/21645515.2018.1540807（PMID 30380986）。
    • 「After removal of duplicates and full text eligibility assessment, 40 studies remained. The aOR for PTB was 0.87 (0.78-0.96), for LBW 0.82 (0.76-0.89), congenital abnormality 1.03 (0.99-1.07), SGA 0.99 (0.94-1.04) and stillbirth 0.84 (0.65-1.08).」
    • 这篇的结局里有流产（fetal death 含 spontaneous abortion），但摘要没给流产的合并数字，所以流产另引 Donahue 2019。
  • Donahue JG 等 (2019). Vaccine 37(44):6673-6681. https://doi.org/10.1016/j.vaccine.2019.09.035（PMID 31540812）。
    • 「We conducted a case-control study over three influenza seasons (2012-13, 2013-14, 2014-15) in the Vaccine Safety Datalink (VSD).」
    • 「Among 627 matched pairs vaccinated in the previous season, no association was found between vaccination in the 1-28 day risk window and SAB (adjusted odds ratio (aOR) 0.9; 95% confidence interval (CI) 0.6-1.5).」
    • 「These findings lend support to current recommendations for influenza vaccination at any time during pregnancy, including the first trimester.」
  • 反方 Donahue JG 等 (2017). Vaccine 35(40):5314-5322. https://doi.org/10.1016/j.vaccine.2017.06.069（PMID 28917295）。
    • 「The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window」
    • 「Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season.」
    • 「This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.」
    • 2019 年那篇开头就写明是回应它：「A recent study reported an association between inactivated influenza vaccine (IIV) and spontaneous abortion (SAB), but only among women who had also been vaccinated in the previous influenza season.」所以条目标「争议」，备注先写 2017 年的信号，再写复查没重现。

7. 中国疾控中心《中国流感疫苗预防接种技术指南（2026—2027）》

  • 发布页：https://www.chinacdc.cn/jkyj/mygh02/jswj2026/202609/t20260902_1839739.html（2026-09-02，无头 Chrome 取得）。全文 PDF：https://www.chinacdc.cn/jkyj/mygh02/jswj2026/202609/P020260902609797521311.pdf（39 页，pdftotext 能逐字抽中文）。2025—2026 版（https://www.chinacdc.cn/jkts/202511/t20251103_313229.html）也核过，孕妇部分措辞基本相同，条目引现行的 2026—2027 版。
  • 优先人群：「（八）孕妇：世界卫生组织、部分国家和地区已将孕妇列为建议优先接种的人群。目前我国已有多款疫苗说明书不再将孕妇作为禁忌人群，且"建议与医生共同进行获益/风险评估后决定"。……本指南建议孕妇可接种疫苗说明书中未把孕妇列为接种禁忌的流感疫苗。」
    • 「多款」不再列为禁忌，意味着还有的说明书仍列为禁忌，所以成本栏和备注写「挑说明书没把孕妇列为禁忌的那一款」。
  • 任何阶段：「孕妇在孕期的任何阶段接种流感疫苗均可以为 6 月龄以下婴儿提供保护，孕晚期接种效果更好。」后面紧跟的数字：「美国一项病例对照研究结果显示，母亲孕晚期接种针对婴儿流感相关住院的 VE 为 52%（95%CI:30%—68%），孕早期或孕中期接种 VE 为 17%（95%CI:-15%—40%）」。这个美国研究的原文没取，条目只写「孕晚期效果更好」，不写这两个数。
  • 减毒活疫苗：「以下人群禁止接种 LAIV：……④孕妇」；「LAIV3 适用于 3—17 岁人群，每剂次 0.2 mL」；「LAIV 的接种采用鼻内喷雾法，严禁注射。」
  • 接种时间：「通常在 11 月份左右进入冬春季流感流行季，建议在 9—10 月完成接种；即使此时间段内未完成接种，整个流行季也都可以接种。」
  • 婴儿家人：优先人群「（六）6 月龄以下婴儿的家庭成员和看护人员」。疫苗适用年龄「可用于 6 月龄及以上人群」，所以备注写孩子不满 6 个月不能打。
  • 指南还写了孕妇接种与子痫前期、流产、胎儿死亡风险更低（HR 0.76、0.61、0.50 等），出自观察研究、原文没取，条目不用。

证据等级与收益量级

  • 证据等级 A：两项随机试验（Zaman、Madhi）加汇总分析，数字具体。标「争议」是因为 Donahue 2017 的流产信号，反方证据和后续复查都写在备注。
  • 收益量级「大」：口径是死亡率（含健康终点）。本条没有死亡率的数字，终点是化验确诊的流感和因流感住院，这是健康终点，不是替代指标。按阈值机械套：孩子确诊流感降 48%（汇总）到 63%（试验），因流感住院降 72%，孕妇因流感住院降 40%，都 ≥20%，定「大」。这和第 1 节第 20 条同口径同档。保守的一端是 Jarvis 只合算两项试验得到的 34%，仍 ≥20%。
  • 受益人：第 ① 档你自己和第 ② 档孩子。

没有采用的

  • CDC 的孕妇流感疫苗页没有单独抓：WHO 和中国疾控指南已能逐字核对同样的意思。
  • 中国疾控指南里孕妇流感「死亡（OR=3.62）」：和 WHO 原文矛盾（WHO 说死亡 OR 1，不显著），没核到出处，不用。