Conclusion
Vaccines currently routinely recommended for pregnant individuals in the U.S. have not been shown to cause spontaneous abortion (SAb).
Why This Is An Issue
The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that “all women who are pregnant or who might be pregnant or postpartum during the influenza season receive influenza vaccine. Any licensed, recommended, and age-appropriate IIV or RIV4 may be used. LAIV4 should not be used during pregnancy. Influenza vaccine can be administered at any time during pregnancy, before and during the influenza season.” 1-3.
The recommendation for IIV in pregnancy was based upon the benefits of the vaccine for prevention of influenza in the mother and infants born to persons immunized in pregnancy, and the overall excellent safety profile of IIV among children and adults 4. SAb is defined in the United States as the loss of a fetus before 20 weeks of gestation (before 24 weeks in some other countries), and occurs in roughly 15-20% of clinically recognized pregnancies 5.
In a 2017 publication, Donahue et al. reported results from a case-control study matched on two age groups examining the risk of SAb following receipt of inactivated influenza vaccines containing A/H1N1pdm2009 antigen in the 2010-11 and 2011-12 seasons 6. The odds of vaccine receipt in the 28-day exposure window were double among women who had an SAb compared with the control women who had live births or stillbirths (adjusted odds ratio: 2.0; 95% confidence interval: 1.1–3.6). In a post-hoc analysis, the study found the risk was almost entirely attributed to women who had received vaccines containing pandemic H1N1 (pH1N1) antigen in the previous year (aOR: 7.7; 95%CI: 2.2–27.3) compared to women unvaccinated in the previous year (aOR: 1.3; 95%CI: 0.7–2.7) 6.
As pointed out by Chambers et al. in an accompanying commentary, SAb is one of the most challenging birth outcomes to study using observational studies. Many clinically unrecognized pregnancies occur and retrospective studies have a difficult time capturing these pregnancies and SAbs 7. Limitations of the 2017 Donahue et al. study include ascertainment of SAb date, the potential that healthcare seeking for SAb care was associated with vaccination, preferential vaccination among women with comorbidities or other risk factors for SAb, the potential that cases had greater opportunity for vaccination because they sought care for symptoms foreshadowing SAb diagnosis, and others discussed in the paper and commentary 6,7. However, a subsequent case-control study from Donahue et al., matched on three age groups and with a population three times the size of the previous study, revealed no significant association between influenza vaccine receipt and SAb, regardless of prior season vaccination status 8.
Epidemiological Evidence
Proposed Biological Mechanism
Infection with wild-type influenza virus during pregnancy can cause life-threatening illness in pregnant individuals and increases the risk of SAb, as demonstrated during the 2009 influenza pandemic 56,57. Inflammation has been linked to pregnancy loss 58-60. Although there is a brief inflammatory response in pregnant and non-pregnant individuals after influenza vaccination 61,62, there is no evidence to support that the brief inflammation is sufficient to cause problems in pregnancy.
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