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

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.

Figure.. Association Between Seasonal Influenza Vaccination in Pregnancy and Pediatric Health Outcomes, by Trimester of Vaccination

^aTiming imputed for 19% of vaccinated group; No. of events and incidence rates in that group based on first imputed data set; adjusted estimates based on 10 imputed data sets. ^bAdjusted using stabilized inverse probability of treatment weights. ^cNo. of events = total children diagnosed with outcome. Point estimates are HRs from a Cox proportional hazards model. ^dSee Table 2. ^eNo. of events = total occurrences for each outcome. Point estimates are incidence rate ratios from a negative binomial model. ^fAll respiratory tract infections, gastrointestinal infections, and otitis media. ^gData suppressed (n < 5).