• 03Apr2018
• Apr 03, 2018

• CDC and ACOG Respond to Flu Vaccine and Miscarriage Concerns

  The CDC has issued a response to the recent paper (Vaccine, 2017) that found an association between influenza vaccination with H1N1pdm09 during the 2010-2011 and 2011-2012 flu seasons.

The CDC ‘Information and Guidance’ provides the following recommendation:

CDC and its Advisory Committee on Immunization Practices (ACIP) are aware of these data, which were first presented to ACIP at a public meeting in June 2015. At this time, CDC and ACIP have not changed the recommendation for influenza vaccination of pregnant women. It is recommended that pregnant women get a flu vaccine during any trimester of their pregnancy because flu poses a danger to pregnant women and a flu vaccine can prevent influenza in pregnant women.

Study Review

Purpose

This study by Donahue et al., (Vaccine, 2017) sought to determine if pH1N1 flu vaccine was associated with spontaneous abortion (SAB)

Methods

• Case Control Study
• Over two seasons (2010-11, 2011-12)
• Used the Vaccine Safety Datalink (VSD)
• Live births or stillbirths and were matched on site, date of last menstrual period, and age
• 919 potential cases identified using diagnosis codes, with 485 eligible on record review

Results

• Among women who received pH1N1-containing vaccine in the previous influenza season, the adjusted odds ratio (aOR) in the 1–28 days was 7.7 (95% CI 2.2–27.3)
• No significant findings if women did not receive pH1N1-containing vaccine in the previous season

Conclusion

• Only significant findings on post-hoc analysis
  • 1-28 day window and if previously received pH1N1-containing vaccine in the previous flu season
• Authors state that this study does not signify causation

Study Limitations

• When assessing primary outcome, flu vaccine and miscarriage, the study did not find an association with vaccine and SAB
  • Post hoc analysis was performed on a small sample size
    • Small subset of patients: 21 miscarriages vs 17 controls (4% of miscarriages studied)
    • Studies with small sample sizes are prone to error
  • Post hoc as per authors means that the research ‘question’ was not an a priori hypothesis but rather continuing analysis after failing to find any statistically significant associations
• Women more at risk of miscarriage may have been more likely to receive vaccine
• SABs are common in early pregnancy and do not necessarily come to attention, so true impact on outcome measure is unknown
  • Unreported miscarriage group may have had fewer vaccines
• Case control is retrospective and provides the odds ratio of having received the vaccine if one had a miscarriage
  • The data cannot be used to predict who will miscarry based on whether or not they received a vaccine
• KEY POINT: Due to early timing (1-28 day window), many women would not have known if they were pregnant when they received their flu shot

Previous Studies

• The CDC provides an extensive list of previous studies indicating that there is no association between flu vaccine and adverse perinatal outcomes
• Håberg et al. (NEJM, 2013) demonstrated a 70% reduction in flu diagnoses when women received vaccine in pregnancy
  • Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI 1.07 to 3.41).
• Two recent studies demonstrated a beneficial association between flu vaccine and perinatal outcomes
  • Legge et al. (CMAJ, 2014) studied a cohort of 1,958 women that demonstrated in women who had influenza vaccine the following
    • Lower preterm birth (aOR 0.75; 95% CI 0.60–0.94)
    • Lower rate of low-birth-weight (LBW) infants (aOR 0.73; 95% CI 0.56–0.95)
  • Bratton et al. (Clinical Infectious Disease, 2015) published a systematic review and meta-analysis that demonstrated in women who had influenza vaccine the following
    • Lower likelihood of stillbirth (relative risk [RR] 0.73; 95% CI 0.56-0.96) with similar findings when restricted to H1N1pdm09 vaccine
    • Pooled estimate for spontaneous abortion was not significant (RR, 0.91; 95% CI, 0.68-1.22)

ACOG Practice Advisory

Following publication of this study, ACOG has released a practice advisory to the Women’s Health community reiterating the importance and safety of influenza vaccination:

In evaluating all the available scientific information, the results from the September 2017 study do not warrant changing the current recommendation. Influenza vaccination remains the best available prevention for serious morbidity related to flu in pregnancy. Therefore, ACOG recommends that ob-gyns continue to encourage routine flu vaccination during pregnancy in any trimester.