Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

doi:10.1136/bmj.l4151

. 2019 Jul 10:366:l4151.

doi: 10.1136/bmj.l4151.

Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

Laura K Walsh^{1

2}, Jessy Donelle³, Linda Dodds⁴, Steven Hawken^{2

3

5}, Kumanan Wilson^{2

3

5}, Eric I Benchimol^{2

3

6}, Pranesh Chakraborty^{2

6}, Astrid Guttmann^{3

7

8}, Jeffrey C Kwong^{3

7

9

10}, Noni E MacDonald⁴, Justin R Ortiz¹¹, Ann E Sprague^{1

2

6}, Karina A Top⁴, Mark C Walker^{1

2

5}, Shi Wu Wen^{2

5}, Deshayne B Fell^{12

3

6}

Affiliations

¹ Better Outcomes Registry & Network, Ottawa, ON, Canada.
² University of Ottawa, Ottawa, ON, Canada.
³ ICES, Toronto, ON, Canada.
⁴ Dalhousie University, Halifax, NS, Canada.
⁵ Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁶ Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada.
⁷ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁸ Hospital for Sick Children, Toronto, ON, Canada.
⁹ Public Health Ontario, Toronto, ON, Canada.
¹⁰ Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
¹¹ University of Maryland School of Medicine, Baltimore, MD, USA.
¹² University of Ottawa, Ottawa, ON, Canada dfell@cheo.on.ca.

PMID: 31292120
PMCID: PMC6614795
DOI: 10.1136/bmj.l4151

Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

Laura K Walsh et al. BMJ. 2019.

. 2019 Jul 10:366:l4151.

doi: 10.1136/bmj.l4151.

Authors

Affiliations

¹ Better Outcomes Registry & Network, Ottawa, ON, Canada.
² University of Ottawa, Ottawa, ON, Canada.
³ ICES, Toronto, ON, Canada.
⁴ Dalhousie University, Halifax, NS, Canada.
⁵ Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁶ Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada.
⁷ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁸ Hospital for Sick Children, Toronto, ON, Canada.
⁹ Public Health Ontario, Toronto, ON, Canada.
¹⁰ Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
¹¹ University of Maryland School of Medicine, Baltimore, MD, USA.
¹² University of Ottawa, Ottawa, ON, Canada dfell@cheo.on.ca.

PMID: 31292120
PMCID: PMC6614795
DOI: 10.1136/bmj.l4151

Abstract

Objective: To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood.

Design: Retrospective cohort study.

Setting: Population based birth registry linked with health administrative databases in the province of Ontario, Canada.

Participants: All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes.

Main outcome measures: Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding.

Results: Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups.

Conclusions: No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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Conflict of interest statement

Competing interests: All authors have completed and submitted the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the work as described above; KAT has received grants from GlaxoSmithKline and personal fees and non-financial support from Pfizer, both of which were unrelated to the submitted work; no other relationships or activities that could appear to have influenced the submitted work.

Figures

**Fig 1**
Flow diagram of study. *Information on maternal 2009 pandemic H1N1 influenza vaccination was collected between 2 November 2009 and 31 October 2010. †Invalid birth date (n=21), duplicate record (n=31), invalid linkage (n=209), women who were not continuously eligible to receive healthcare in Ontario during pregnancy or infant not eligible at birth for provincial healthcare (n=13 426)

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References

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1. Centers for Disease Control Influenza. In: Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed Public Health Foundation, 2012.
1. Steinhoff MC. Epidemiology and prevention of influenza. In: Nelson K, Masters Williams C, eds. Infectious Disease Epidemiology. Theory and Practice. 2nd ed Jones and Bartlett Publishers, 2007: 577-600.
1. Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013;347:f5061. 10.1136/bmj.f5061 - DOI - PMC - PubMed
1. Siston AM, Rasmussen SA, Honein MA, et al. Pandemic H1N1 Influenza in Pregnancy Working Group Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010;303:1517-25. 10.1001/jama.2010.479 - DOI - PMC - PubMed

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[1] Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med 2008;121:258-64. 10.1016/j.amjmed.2007.10.040 - DOI - PMC - PubMed

[2] Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med 2008;121:258-64. 10.1016/j.amjmed.2007.10.040 - DOI - PMC - PubMed

[3] Centers for Disease Control Influenza. In: Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed Public Health Foundation, 2012.

[4] Centers for Disease Control Influenza. In: Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed Public Health Foundation, 2012.

[5] Steinhoff MC. Epidemiology and prevention of influenza. In: Nelson K, Masters Williams C, eds. Infectious Disease Epidemiology. Theory and Practice. 2nd ed Jones and Bartlett Publishers, 2007: 577-600.

[6] Steinhoff MC. Epidemiology and prevention of influenza. In: Nelson K, Masters Williams C, eds. Infectious Disease Epidemiology. Theory and Practice. 2nd ed Jones and Bartlett Publishers, 2007: 577-600.

[7] Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013;347:f5061. 10.1136/bmj.f5061 - DOI - PMC - PubMed

[8] Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013;347:f5061. 10.1136/bmj.f5061 - DOI - PMC - PubMed

[9] Siston AM, Rasmussen SA, Honein MA, et al. Pandemic H1N1 Influenza in Pregnancy Working Group Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010;303:1517-25. 10.1001/jama.2010.479 - DOI - PMC - PubMed

[10] Siston AM, Rasmussen SA, Honein MA, et al. Pandemic H1N1 Influenza in Pregnancy Working Group Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010;303:1517-25. 10.1001/jama.2010.479 - DOI - PMC - PubMed

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Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

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Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

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