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Infectious Diseases

Association of Maternal Influenza Vaccination During Pregnancy With Early Childhood Health Outcomes

Educational Objective
To understand the benefits of seasonal influenza vaccination administered during pregnancy.

1 Credit CME

JAMA

Published Online: June 8, 2021

Original Investigation

Article Information and Disclosures

Azar Mehrabadi, PhD^1,2;

Linda Dodds, PhD^1,2;

Noni E. MacDonald, MD, MS²;

Karina A. Top, MD, MS²;

Eric I. Benchimol, MD, PhD^3,4,5;

Jeffrey C. Kwong, MD, MSc^5,6,7,8;

Justin R. Ortiz, MD, MS⁹;

Ann E. Sprague, PhD^10,11;

Laura K. Walsh, MS¹²;

Kumanan Wilson, MD, MSc^13,14;

Deshayne B. Fell, PhD^5,11,12

Author Affiliations

¹Departments of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada
²Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
³Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
⁴Division of Gastroenterology, Hepatology and Nutrition and Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
⁵ICES, Toronto, Ontario, Canada
⁶Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
⁷Public Health Ontario, Toronto, Ontario, Canada
⁸Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
⁹Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore
¹⁰Better Outcomes Registry & Network, Ottawa, Ontario, Canada
¹¹Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Ontario, Canada
¹²School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
¹³Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
¹⁴Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

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Key Points

Question Is seasonal influenza vaccination in pregnancy associated with adverse childhood health outcomes?

Findings In this population-based retrospective cohort study that used inverse probability of treatment weighting and included 28 255 children with a mean duration of follow-up of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with the risk of immune-related health outcomes (eg, asthma, infections) non–immune-related outcomes (eg, neoplasms, sensory impairment), or nonspecific health outcomes (eg, emergency visits, hospitalizations).

Meaning Seasonal influenza vaccination in pregnancy was not significantly associated with adverse early childhood health outcomes among offspring.

Abstract

Importance Seasonal influenza vaccination in pregnancy can reduce influenza illness among pregnant women and newborns. Evidence is limited on whether seasonal influenza vaccination in pregnancy is associated with adverse childhood health outcomes.

Objective To assess the association between maternal influenza vaccination during pregnancy and early childhood health outcomes.

Design, Setting, and Participants Retrospective cohort study, using a birth registry linked with health administrative data. All live births in Nova Scotia, Canada, between October 1, 2010, and March 31, 2014, were included, with follow-up until March 31, 2016. Adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) with 95% confidence intervals were estimated while controlling for maternal medical history and other potential confounders using inverse probability of treatment weighting.

Exposures Seasonal influenza vaccination during pregnancy.

Main Outcomes and Measures Childhood outcomes studied were immune-related (eg, asthma, infections), non–immune-related (eg, neoplasms, sensory impairment), and nonspecific (eg, urgent or inpatient health care utilization), measured from emergency department and hospitalization databases.

Results Among 28 255 children (49% female, 92% born at ≥37 weeks’ gestation), 10 227 (36.2%) were born to women who received seasonal influenza vaccination during pregnancy. During a mean follow-up of 3.6 years, there was no significant association between maternal influenza vaccination and childhood asthma (incidence rate, 3.0 vs 2.5 per 1000 person-years; difference, 0.53 per 1000 person-years [95% CI, −0.15 to 1.21]; adjusted HR, 1.22 [95% CI, 0.94 to 1.59]), neoplasms (0.32 vs 0.26 per 1000 person-years; difference, 0.06 per 1000 person-years [95% CI, −0.16 to 0.28]; adjusted HR, 1.26 [95% CI, 0.57 to 2.78]), or sensory impairment (0.80 vs 0.97 per 1000 person-years; difference, −0.17 per 1000 person-years [95% CI, −0.54 to 0.21]; adjusted HR, 0.82 [95% CI, 0.49 to 1.37]). Maternal influenza vaccination in pregnancy was not significantly associated with infections in early childhood (incidence rate, 184.6 vs 179.1 per 1000 person-years; difference, 5.44 per 1000 person-years [95% CI, 0.01 to 10.9]; adjusted IRR, 1.07 [95% CI, 0.99 to 1.15]) or with urgent and inpatient health services utilization (511.7 vs 477.8 per 1000 person-years; difference, 33.9 per 1000 person-years [95% CI, 24.9 to 42.9]; adjusted IRR, 1.05 [95% CI, 0.99 to 1.16]).

Conclusions and Relevance In this population-based cohort study with mean follow-up duration of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with an increased risk of adverse early childhood health outcomes.

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Article Information

Corresponding Author: Deshayne B. Fell, PhD, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, 401 Smyth Rd, Centre for Practice Changing Research, Room L-1154, Ottawa, ON K1H 8L1, Canada (dfell@cheo.on.ca).

Accepted for Publication: April 15, 2021.

Author Contributions: Dr Mehrabadi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Mehrabadi, Dodds, MacDonald, Benchimol, Ortiz, Sprague, Walsh, Wilson, Fell.

Acquisition, analysis, or interpretation of data: Mehrabadi, Dodds, MacDonald, Top, Benchimol, Kwong, Ortiz, Fell.

Drafting of the manuscript: Mehrabadi, Fell.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Mehrabadi, Dodds, Fell.

Obtained funding: Dodds, Ortiz, Fell.

Administrative, technical, or material support: Dodds, Benchimol, Kwong, Sprague.

Supervision: Wilson, Fell.

Conflict of Interest Disclosures: Dr Top reported receiving consultancy fees from Pfizer and receiving grants from GlaxoSmithKline. Dr Benchimol reported receiving legal consulting fees from Hoffmann La-Roche Limited for matters unrelated to the influenza and other vaccine products. Dr Ortiz reported receiving consultancy fees from Pfizer, Foundation for Influenza, and Seqirus and receiving research support paid to his research unit from the National Institutes of Health, Pfizer, and GlaxoSmithKline. Dr Wilson is CEO of CANImmunize Inc, which hosts a national digital immunization record. No other authors reported disclosures.

Funding/Support: This study was funded by Canadian Institutes of Health Research operating grant AO1-151541.

Role of the Funder/Sponsor: The Canadian Institutes of Health Research had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The data (or portions of the data) used in this report were made available by Health Data Nova Scotia of Dalhousie University. Although this research is based on data obtained from the Nova Scotia Department of Health and Wellness, the observations and opinions expressed are those of the authors and do not represent those of either Health Data Nova Scotia or the Department of Health and Wellness.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.