Influenza Vaccination of Pregnant Women and Serious Adverse Events in the Offspring
Abstract
:1. Introduction
2. Objective, Materials, and Methods
3. Results and Their Discussion
3.1. Observational Studies and Healthy-Vaccinee Bias
3.2. RCTs: Some New Evidence
- ➢
- These presumed/neonatal infections were SAEs, not generic infections
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- the total SAEs (which included infant deaths: 52 vs. 37 in the control group) were also significantly more in the offspring of vaccinated mothers
- ➢
- the total SAEs (not just the individual categories of SAEs) are indeed a “hard” standard outcome.
3.3. General Comments
4. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Author (Surname) | Name, Article Year [Ref. Number] Participants | Journal | Important Findings |
---|---|---|---|
Kahn | Influenza Tdap vaccination coverage among pregnant women, 2018 [13] | MMWR | This U.S. survey shows a quantitative view of the size of the possible healthy-vaccinee bias. Its inadequate correction might explain the worse outcomes of the offspring of unvaccinated women |
Freund | COFLUPREG, 2011 [14] | PLoS ONE | This French survey shows a quantitative view of the size of the healthy-vaccinee bias in a European country. Inadequate correction of this bias might explain the differences in the offspring’s outcomes |
Giles | The safety of IIV in pregnancy for birth outcomes: a systematic review, 2018 (39 observational studies and one RCT) [17] | Hum Vaccin Immunother | Only preterm birth and low birth weight showed a significant advantage in offspring of vaccinated mothers (aOR 0.87 and 0.82, respectively). No other outcome showed any significant differences |
Jeong | Effects of maternal influenza vaccination on adverse birth outcomes: a systematic reviews and Bayesian meta-analysis, 2019 (41 cohort, 5 case-control studies, and two RCTs) [19] | PLoS ONE | This most recent and comprehensive systematic review found no significant decrease in any of the adverse fetal outcomes: preterm birth, low birth weight, small for gestational age, congenital malformation, fetal death |
Madhi | Matflu, 2014 [18] | New Engl J Med | NNV = 55 (mothers), 56 (children) |
Severe safety signals (no significant differences): | |||
(influenza vaccinated vs. placebo) | |||
Maternal deaths: 2 vs. 0 | |||
Maternal hospitalization for any infection: 16 vs. 7 | |||
Miscarriages: 3 vs. 5 (4?) | |||
Stillbirths: 15 vs. 9 | |||
Infant deaths: 15 vs. 21 | |||
Infant hospitalization for sepsis in the first 28 days of birth: 16 vs. 10 | |||
Infant hospitalization for meningitis in the first 28 days: 6 vs. 2 | |||
Steinhoff | Nepalese trial, 2017 [20] | Lancet Infect Dis | NNV = about 20 (not specified) |
Severe safety signals (no significant differences): | |||
(influenza vaccinated vs. placebo) | |||
Maternal deaths: 3 vs. 5 in the abstract (2 vs. 5 in STable2) | |||
Miscarriages: 5 vs. 3 | |||
Stillbirths: 33 vs. 31 | |||
Infant deaths: 61 vs. 50 in the abstract (60 vs. 51 in STable2) | |||
Congenital defects: 20 vs. 18 | |||
Zaman | Mother’sGift project, 2008 [27] | New Engl J Med | NNV = 17 |
Severe safety signals (no significant differences): | |||
(influenza vaccinated vs. pneumococcal) | |||
Maternal deaths: 0 vs. 0 | |||
Fetal + infant deaths: 4 vs. 2 | |||
Tapia | Mali trial, 2016 [28] | Lancet Infect Dis | NNV = 99 |
Severe safety signals (no significant differences, except presumed serious neonatal infections and total SAEs): | |||
(influenza vaccinated vs. meningococcal) | |||
Maternal deaths: 1 vs. 0 (in Table S6: SAEs in participating women ‘at any time after vaccination until 6 months post-partum’), but 2 vs. 3 (in the article) | |||
Stillbirths: 24 vs. 30 | |||
Infant deaths: 52 vs. 37 | |||
Presumed serious neonatal infections: 60 vs. 37 (p = 0.02) | |||
Total SAEs: 225 vs. 175 (p = 0.01); excluding major congenital malformations 219 vs. 171 (p = 0.015) | |||
Simões | Matflu (reanalysis) 2019 [29] | Vaccine | Serious safety signals (no significant differences): |
(influenza vaccinated vs. placebo) | |||
Fetal death: 16 vs. 13 (RR 1.21) | |||
Preterm birth: 100 vs. 80 (RR 1.22) | |||
Low birth weight: 123 vs. 107 (RR 1.21) | |||
Small for gestational age: 156 vs. 138 (RR 1.21) |
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Donzelli, A. Influenza Vaccination of Pregnant Women and Serious Adverse Events in the Offspring. Int. J. Environ. Res. Public Health 2019, 16, 4347. https://doi.org/10.3390/ijerph16224347
Donzelli A. Influenza Vaccination of Pregnant Women and Serious Adverse Events in the Offspring. International Journal of Environmental Research and Public Health. 2019; 16(22):4347. https://doi.org/10.3390/ijerph16224347
Chicago/Turabian StyleDonzelli, Alberto. 2019. "Influenza Vaccination of Pregnant Women and Serious Adverse Events in the Offspring" International Journal of Environmental Research and Public Health 16, no. 22: 4347. https://doi.org/10.3390/ijerph16224347