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The Relationship Between 2009 Pandemic H1N1 Influenza During Pregnancy and Preterm Birth: A Population-based Cohort Study

Fell, Deshayne B.a–d; Platt, Robert W.d; Basso, Olgad,e; Wilson, Kumananc,f,g; Kaufman, Jay S.d; Buckeridge, David L.d; Kwong, Jeffrey C.c,h–k

doi: 10.1097/EDE.0000000000000753
Infectious diseases

Background: Previous studies of maternal influenza illness and preterm birth have yielded inconsistent results. Our objective was to assess the association between 2009 pandemic H1N1 (pH1N1) influenza during pregnancy and preterm birth in a large obstetrical population.

Methods: We linked a province-wide birth registry with health administrative databases to identify influenza-coded hospitalizations, emergency department visits, or physician visits among pregnant women during the 2009 H1N1 pandemic (our proxy for clinical pH1N1 influenza illness). Using Cox regression, we estimated adjusted hazard ratios (aHR) for preterm birth and spontaneous preterm birth treating influenza as a time-varying exposure.

Results: Among 192,082 women with a singleton live birth, 2,925 (1.5%) had an influenza-coded health care encounter during the 2009 H1N1 pandemic. Compared with unexposed pregnancy time, there was no association between exposure to the pandemic, with or without clinical influenza illness, and preterm birth (no pH1N1 diagnosis: aHR = 1.0; 95% confidence interval [CI] = 0.98, 1.1; pH1N1 diagnosis: aHR = 1.0; 95% CI = 0.88, 1.2). Among women with preexisting medical conditions, influenza was associated with increased preterm birth (aHR = 1.5; 95% CI = 1.1, 2.2) and spontaneous preterm birth (aHR = 1.7; 95% CI = 1.1, 2.6), and these associations were strongest in the third trimester and when data were analyzed to allow for a transient acute effect of influenza.

Conclusions: In the general obstetrical population, there was no association between pH1N1 influenza illness and preterm birth, but women with preexisting medical conditions known to increase the risk of influenza-associated morbidity were at elevated risk.

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From the aChildren’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; bSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada; cInstitute for Clinical Evaluative Sciences, Ottawa and Toronto, Canada; dDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; eDepartment of Obstetrics and Gynecology, McGill University, Montreal, Canada; fDepartment of Medicine, University of Ottawa, Ottawa, Canada; gClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; hDepartment of Family and Community Medicine, University of Toronto, Toronto, Canada; iDalla Lana School of Public Health, Toronto, Canada; jPublic Health Ontario, Toronto, Canada; and kUniversity Health Network, Toronto, Canada.

Submitted January 30, 2017; accepted September 14, 2017.

The authors report no conflicts of interest.

This study was partially funded through an Operating Grant from the Canadian Institutes for Health Research (#MOP-119570). This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.

The dataset from this study is held securely in coded form at the Institute for Clinical Evaluative Sciences (ICES). Although data-sharing agreements prohibit ICES from making the data set publicly available, access may be granted to those who meet prespecified criteria for confidential access, available at

The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. Parts of this material are based on data and information compiled and provided by the Canadian Institute of Health Information (CIHI). However, the analyses, conclusions, opinions, and statements expressed herein are those of the authors and not necessarily those of CIHI. No endorsement by Institute for Clinical Evaluative Sciences, the Ontario Ministry of Health and Long-Term Care, or CIHI is intended or should be inferred.

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Correspondence: Deshayne B. Fell, Children’s Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Centre for Practice Changing Research, Room L-1154, Ottawa, Ontario, K1H 8L1, Canada. E-mail:

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