While certainly not a state of disease, pregnancy presents with specific health risks for both mother and child. Influenza virus (“the flu”) infections are seasonal: they typically begin in October and can extend into May [1]. Given that pregnancy typically lasts around 9 months, it is a guarantee that influenza virus will be circulating at some point during gestation. Getting the flu while pregnant can increase the risk of negative outcomes, including maternal hospitalization, fetal death, stillbirth, congenital defects, preterm labor, low birth weight, pneumonia, and increased chance of admission to the neonatal intensive care unit [2].
Seasonal influenza vaccination is the most effective way to prevent influenza infection, but only around 60% of pregnant patients are receiving this vaccination [3]. This has been attributed to incorrect perceptions about the vaccine: “A significant proportion [of unvaccinated individuals] believe that the influenza vaccine can increase the risk of miscarriage, birth defects, and fever, and may be harmful during pregnancy or breastfeeding” [2]. While the vaccine is significantly less than 100% effective (2018 estimates from CDC show total efficacy at 36%, ranging from 25-67% depending on viral strain [4]), it if effective at reducing negative outcomes [2], and is recommended for all individuals over 6 months of age. In the case of pregnancy and early life, there is an additional benefit is the transfer of maternal antibodies through the placenta, which offers a newborn protection against the virus. Since the flu vaccine is not recommended until 6 months of age, this protection is extremely important during the first 6 months of life.
Safety of influenza vaccination during pregnancy
There was significant press coverage of a study published in 2017 that showed an increase in miscarriage rate in pregnant women who received seasonal influenza vaccine. The vaccine in question included coverage for the pandemic H1N1 strain during the 2010-2011 and 2011-2012 flu seasons [5]. This association was sensationally reported (and seized upon by anti-vaccine advocates) as definitive proof that vaccines are dangerous for pregnant patients. In my office, I certainly had many questions about this study and the associated media reporting, and had to dig into the research to find reliable answers.
This study was interesting for a number of reasons. It contradicted previous high quality studies which revealed no increased fetal risk from vaccination [6,8]. The new research was a case-control study, and these data were analyzed post-hoc. This means that the researchers were not intending to study the relationship between sequential vaccination and miscarriage, and their study was was not designed or powered to evaluate this risk. Additionally, only the odds-ratio was investigated [7] (more information on the different types of medical studies can be found here, and the difference between odds-ratio and risk is discussed here). It is also important to note that miscarriages reported in the new research were associated with other factors that differed between the cases and controls. Among other risk factors, those who miscarried were more likely to be overweight, over age 35, and smoke during pregnancy. Not all of these factors were completely controlled for, which makes it more difficult to evaluate if the findings are accurate. It is also worth noting that the research team was transparent about this shortcoming in their dataset [5].
Given these limitations, a single contradictory study should not be leveraged to alter recommendations that support vaccination. The Advisory Committee on Immunization Practices (ACIP) reviewed this study’s data and its limitations in 2015 and concluded “These findings are preliminary and are inconsistent with prior research on IIV [inactivated influenza vaccine] safety and pregnancy, including the prior VSD study and meta-analysis… No new safety concerns during the 2014-2015 influenza season have been detected through VAERS surveillance” [9].
Maternal inflammation and negative outcomes
I recently saw an article suggesting that vaccine-induced inflammation during pregnancy was harmful to the developing fetus (note: the article has since been removed). Using a unrelated study [10] to support this argument, the author’s contention was that reducing sources of inflammation in pregnancy should include deferring vaccines.
This is not only a gross misinterpretation of the research, but irresponsibly promotes baseless fears regarding vaccination during pregnancy. The immune activity induced by the seasonal influenza vaccine is minimal comparison to the inflammatory cytokines released during infection with the influenza virus itself. For infants born during influenza season, the passive immunity gained from anti-influenza antibodies in breast milk is also beneficial and protective.
Anything — whether it is food, medication, supplement, vaccine or pathogen — that you come in contact will interact with your immune system, generally inducing some level of cytokine response. The flu vaccine is unlikely to be a primary driver of inflammation during pregnancy, and the overwhelming majority of research evidence supports that this vaccine is safe during pregnancy. In contrast, the influenza virus is a very real and potentially serious inflammatory condition, with clear maternal and fetal risks.
The question then must focus on how we weigh available evidence, and the risks/benefits of vaccination during pregnancy. The evidence is overwhelmingly clear: influenza vaccination during pregnancy helps prevent severe adverse events. It is not 100% effective, but when combined with simple measures such as good hand hygiene and avoiding individuals who are ill, it is the best preventive measure available.
Equally clear is that pregnant patients have an increased vulnerability to influenza infection, and contracting the flu during pregnancy is dangerous for both mother and child. Even a modest reduction in the instance of adverse outcomes in pregnancy warrants a strong recommendation, and routine use of the seasonal influenza vaccine during pregnancy should be strongly encouraged.
References
- “The Flu Season.” www.cdc.gov/flu/about/season/flu-season.htm.
- Yudin, Mark. “Risk Management of Seasonal Influenza during Pregnancy: Current Perspectives.” International Journal of Women’s Health, 2014, p. 681., doi:10.2147/ijwh.s47235.
- “Influenza Vaccination Coverage During Pregnancy — Selected Sites, United States, 2005–06 Through 2013–14 Influenza Vaccine Seasons.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 14 Aug. 2017, www.cdc.gov/mmwr/volumes/65/wr/mm6548a3.htm.
- “Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness — United States, February 2018.” Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness — United States, February 2018, 16 Feb. 2018, www.cdc.gov/mmwr/volumes/67/wr/mm6706a2.htm.
- Donahue, James G., et al. “Association of Spontaneous Abortion with Receipt of Inactivated Influenza Vaccine Containing H1N1pdm09 in 2010-11 and 2011-12.” Vaccine, vol. 35, no. 40, 2017, pp. 5314–5322., doi:10.1016/j.vaccine.2017.06.069.
- Håberg, Siri E., et al. “Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination.” New England Journal of Medicine, vol. 368, no. 4, 2013, pp. 333–340., doi:10.1056/nejmoa1207210.
- Crawford, Chris. “CDC Breaks Down Recent Study Linking Flu Vaccine, Miscarriage.” CDC Breaks Down Recent Study Linking Flu Vaccine, Miscarriage, 20 Sept. 2017, 12:47, www.aafp.org/news/health-of-the-public/20170920flumiscarry.html.
- Irving, Stephanie A., et al. “Trivalent Inactivated Influenza Vaccine and Spontaneous Abortion.” Obstetrics & Gynecology, vol. 121, no. 1, 2013, pp. 159–165., doi:10.1097/aog.0b013e318279f56f.
- ACIP Summary Report, June 24-25 2015. https://www.cdc.gov/vaccines/acip/meetings/downloads/min-archive/min-2015-06.pdf
- Spann, Marisa N., et al. “Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.” The Journal of Neuroscience, vol. 38, no. 11, 2018, pp. 2877–2886., doi:10.1523/jneurosci.2272-17.2018.
Maxwell Cohen, ND
Max Cohen, ND is a naturopathic physician in Portland, Oregon. He currently works for a Federally Qualified Health Center (FQHC) providing primary care for a wide variety of patients. He is a member of the Board of Directors of the Naturopathic Academy of Primary Care Providers (NAPCP), as well as the Scientific Advisory Board for Boost Oregon.He completed his medical training and residency at the National University of Natural Medicine. Prior to medical school he worked as a microbiologist in a tuberculosis vaccine development lab. Twitter @MaxwellCohenND
