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Original Investigation
June 8, 2021

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

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
JAMA. 2021;325(22):2285-2293. doi:10.1001/jama.2021.6778
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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