Maternal influenza vaccine during pregnancy not linked to adverse early childhood outcomes

1. Over a mean follow-up period of 3.6 years, no significant association was detected between maternal influenza vaccination during pregnancy and early childhood health outcomes including pediatric asthma, neoplasms and sensory impairment.

Evidence Rating: 2 (Good)

Study Rundown: Vaccine hesitancy, particularly during pregnancy and early childhood, is a key issue that presents ongoing challenges for pediatric healthcare providers. This population-based retrospective cohort study sought to evaluate the relationship between maternal exposure to the influenza vaccine during pregnancy and early childhood adverse health outcomes. A total of 28,255 eligible live births occurring during the study period were followed, 10,227 (36.2%) of whom had been exposed to influenza vaccine in utero. No significant associations were found between in-utero influenza vaccine exposure and the following early childhood outcomes assessed from birth until 2016: pediatric asthma, neoplasms, sensory impairment, overall infections or health service utilization. With respect to specific infections, no statistically significant relationship was found between the exposure and upper and lower respiratory tract infections, gastrointestinal infections and acute otitis media. A post-hoc analysis evaluating the timing of the influenza vaccine (first, second, third trimester), however, did find that a third trimester influenza vaccination was significantly associated with lower respiratory tract infections in early childhood. Mehrabad et al’s study has a number of strengths, primarily including its large data set and thorough statistical workup. The inclusion of all eligible live births over four years is an asset, however the population-based study design necessitated by such a large sample size renders it difficult to assess individual data points and identify confounders.  A thoughtful post-hoc analysis of vaccine timing during pregnancy was also an asset. Another strength of this work is that it further reinforces the findings of previous studies on the subject of maternal influenza vaccination and child health. In terms of limitations, misclassification bias must be considered, as some data points were self-reported and several outcomes derived from the databases in this study have not been validated. However, the authors made efforts to control for confounding through the use of sensitivity analyses which confirmed the findings reported here, as well as propensity scoring.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Early childhood health outcomes following in utero exposure to influenza vaccines: a systematic review

In Depth [retrospective cohort study]: Data sources for this study included Nova Scotia’s Atlee Perinatal Database and physician billing codes to identify influenza vaccination status and other prenatal data; hospitalization and physician billing codes were used to assess outcomes. Prespecified immune-related outcomes included asthma and outcomes, on the hypothesis that the fetal immune system may be affected by maternal vaccination. Other outcomes were classified as non-immune (neoplasms, sensory impairment) and non-specific (emergency visits, hospitalizations). A slew of confounders were assessed and controlled for using sensitivity analysis and propensity scoring. Missing data was accounted for through imputation. Outcomes were reported in incidence per 1000 person-years for each cohort. The relationship between cohorts was reported using rate differences and 95% confidence intervals. The adjusted rate ratios between in-utero influenza vaccine and immune outcomes were reported as 1.22 (95% Confidence Interval [CI] 0.94 to 1.59) for pediatric asthma, and 1.07 (95% CI 0.99 to 1.15) for overall infections. The adjusted rate ratio between the exposure and overall healthcare service utilization was 1.05 (95% CI 0.99 to 1.16).

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