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The Risks and Benefits of Repeated First Trimester Influenza Vaccination Against Pandemic H1N1

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, September 15, 2017

One of the cornerstones of pregnancy management, stemming from the unequivocally heightened risk of this condition for severe influenza, has been to routinely immunize all pregnant women against influenza. The influenza vaccine has been shown in multiple studies not to confer any increased risk to the pregnancy. A new study, published in Vaccine, in which the rate of miscarriage was found to increase subsequent to first trimester vaccination against particular strains of the virus, is likely to spark policy discussions regarding this practice.


2010-11, 2011-12 Flu Seasons Studied

In this case control study, conducted using the Vaccine Safety Datalink, a research team led by Belongia, one of the articles’ authors, matched pregnant women who were vaccinated and had spontaneous abortions with those who did not. In the particular flu seasons studied, the vaccine components were identical, and both, notably, included the 2009 H1N1 pandemic strain. A total of 485 cases were studied. Cases were more likely to be older, to be African-American, to have experienced 2 or more prior miscarriages, and to be smokers. There was no difference in which vaccine manufacturer’s product was used.

For women who had a spontaneous abortion within 28 days of vaccine, the adjusted odds ratio was 2. In a hypothesis-generating post hoc analysis, it was discovered that prior season vaccination against the pandemic H1N1 strain was possibly contributory. Women who did not receive flu vaccine in the season immediately prior had no increased risk.


Important Questions but Limitations to the Study

This study raises important questions for further study, but the findings must be placed in the proper context. It is essential to understand that the striking findings arose from a post hoc analysis and were not part of the primary analysis or an a priori hypothesis. As such, the study in and of itself should not be used to change policy, as correlation is not causation and the threat of flu to pregnant women is real. 

Multiple other studies have not shown this association during pre-pandemic seasons and even with the pandemic vaccine itself. However, there is hypothetical concern that sequential annual vaccination with the same strainin this case, the antigenically distinct pandemic H1N1 viruscould induce enhanced inflammation, leading to this result. The authors are already studying records from subsequent years to ascertain whether the effect was present in the 2012-13, 2013-14, and 2014-15 seasons. The results of these studies, if they hold, might modify recommendations in the future for the trimester in which vaccination should ideally be given.

For the upcoming influenza season, it is important that women and others be vaccinated against influenza. The risk of influenza to pregnant women is real and proven, while these findings need further validation before biological causation can be established. However, the findings underscore the need for a universal influenza vaccine that would obviate concerns over repeated vaccinations.



Donahue JG, Kieke BA, King JP, et al. Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010-11 and 2011-12. Vaccine 2017;35:5314-5322.