Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort studyBMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4151 (Published 10 July 2019) Cite this as: BMJ 2019;366:l4151
- Laura K Walsh, data analyst1 2,
- Jessy Donelle, data analyst3,
- Linda Dodds, professor4,
- Steven Hawken, assistant professor and scientist2 3 5,
- Kumanan Wilson, professor and senior scientist2 3 5,
- Eric I Benchimol, associate professor and scientist2 3 6,
- Pranesh Chakraborty, associate professor and investigator2 6,
- Astrid Guttmann, professor and chief science officer3 7 8,
- Jeffrey C Kwong, associate professor and senior scientist3 7 9 10,
- Noni E MacDonald, professor4,
- Justin R Ortiz, associate professor11,
- Ann E Sprague, associate professor1 2 6,
- Karina A Top, assistant professor and investigator4,
- Mark C Walker, professor and chief of obstetrics and gynecology1 2 5,
- Shi Wu Wen, professor and senior scientist2 5,
- Deshayne B Fell, assistant professor and scientist2 3 6
- 1Better Outcomes Registry & Network, Ottawa, ON, Canada
- 2University of Ottawa, Ottawa, ON, Canada
- 3ICES, Toronto, ON, Canada
- 4Dalhousie University, Halifax, NS, Canada
- 5Ottawa Hospital Research Institute, Ottawa, ON, Canada
- 6Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- 7Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- 8Hospital for Sick Children, Toronto, ON, Canada
- 9Public Health Ontario, Toronto, ON, Canada
- 10Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
- 11University of Maryland School of Medicine, Baltimore, MD, USA
- Correspondence to: D Fell
- Accepted 21 May 2019
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.
Contributors: All authors contributed to the study concept and design, as well as the acquisition, analysis, or interpretation of data. LKW and JD did the statistical analysis. DBF and LKW drafted the manuscript. All authors critically reviewed the manuscript for important intellectual content. DBF obtained the funding and supervised the study. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. DBF had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. LKW and DBF are the guarantors.
Funding: This research was supported by an operating grant from the Canadian Institutes of Health Research (AO1-151541) and by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long term Care (MOHLTC). EIB is supported by a new investigator award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. He is also supported by the Career Enhancement Program of the Canadian Child Health Clinician Scientist Program. JCK is supported by a clinician-scientist award from the Department of Family and Community Medicine, University of Toronto. The funders of this research were not involved in the study design, data analysis, or manuscript preparation or publication decisions. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.
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.
Ethical approval: This study received approval from the Ottawa Health Science Network Research Ethics Board (protocol No 20170431- 01H), the Children’s Hospital of Eastern Ontario Research Ethics Board (protocol No 17/04PE), and the ICES Privacy Office (protocol No 2018 0901 137 000).
Data sharing: The dataset from this study is held securely in coded form at ICES. Although data sharing agreements prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS. The full dataset creation plan and underlying analytic code are available from the authors on request, understanding that the computer programs may rely on coding templates or macros that are unique to ICES and, therefore, either are inaccessible or may need modification.
Transparency: The manuscript’s guarantors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.
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