No association between influenza vaccine exposure in utero and adverse childhood health outcomes

1. In a systematic review, in utero exposure to influenza vaccine was not associated with adverse health outcomes in children older than 6 months of age.

2. All-cause morbidity and mortality, infectious, autoimmune, atopic, and neurodevelopmental outcomes were examined in the study, which included data from over 750,000 children.

Evidence Rating Level: 2 (Good)

Study Rundown: Influenza while seemingly common, is a respiratory infection that can be life threatening, particularly in young children and pregnant women. Influenza vaccination of pregnant women has been shown to reduce the risk of serious illness in infants during the first 6 months of life. However, skepticism of adverse effects of the vaccine has led to low rates of immunization amongst pregnant women. This study is the first systematic review to assess long term health outcomes in children who were exposed to maternal influenza vaccine in utero. Studies that examined health outcomes of children between age 6 months and 5 years were included in the review, encompassing hundreds of thousands of children. No statistically significant association was found between in utero exposure to influenza vaccine and all cause morbidity and mortality as well as a number of infectious, autoimmune, and neurodevelopmental outcomes. Meta-analyses were not possible due to the small number of studies available. Generalization of the results is limited by the fact that most studies examined exposure to pandemic (not seasonal) influenza vaccines, and all of them were conducted in high income countries in North America or Europe. Nonetheless, the results provide further evidence that maternal immunization with influenza vaccine is unlikely to cause adverse childhood health outcomes and can confidently be recommended to pregnant women.

Click to read the study, published today in Pediatrics

Click to read an accompanying editorial in Pediatrics

Relevant Reading: Effectiveness of maternal influenza immunization in mothers and infants

In-Depth [systematic review]: Nine studies including information on 750,000 children were were included in the systematic review. 163,924 of these children were exposed to influenza vaccine in utero. 1 study was a randomized control trial, 5 were retrospective cohort studies, 2 were prospective cohort studies, and 1 was a case control study. Six of the studies involved pandemic influenza vaccines while 3 investigated seasonal vaccines. Five out of 9 of the studies were deemed to be at high risk of bias. Length of follow up was generally between 1 to 5 years in most studies, although one study followed children until age 15 years. Several studies reported statistically significant associations between influenza vaccine and specific outcomes including an inverse association between maternal vaccination and upper respiratory infections (aRR 0.92, 95% CI 0.85-0.99) and all cause hospitalizations (aHR for 5-year hospitalization 0.95, 95% CI 0.91-0.99). One study found a small increased risk of asthma in exposed children (aHR 1.05, 95% CI 1.02-1.09), and other studies reported increased risk for several specific conditions. However, after adjusting for multiple endpoints using the Bonferroni method, these outcomes were not statistically significant.

Image: PD

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