But only nine of over 3,000 studies met the inclusion criteria for a systematic review

Influenza vaccination during pregnancy was not linked with various long-term adverse health outcomes in infants and young children, researchers reported, although the number of studies that addressed these outcomes was small.

Based on a systematic review, “studies to-date have not revealed any adverse effect of maternal influenza vaccination on childhood health outcomes during the first 5 years,” according to Damien Y.P. Foo, BSc, of Curtin University in Perth, Australia, and co-authors.

However, less than a dozen of more than 3,500 studies evaluated met the inclusion criteria for the study, they noted in Pediatrics.

While one study suggested a possible “increased risk of autism spectrum disorder (ASD) after exposure to seasonal [influenza vaccine] in utero, after adjusting for multiple comparisons using Bonferroni-corrected CIs, [the association was] no longer statistically significant,” the authors explained.

They stressed that “additional epidemiological studies of early childhood health outcomes after maternal influenza vaccination are still needed.”

While the analysis by Foo’s group was “solid… all the studies that met inclusion criteria originated from North America or Europe, with no data from low- and middle-income countries,” pointed out Flor M. Munoz, MD, of Baylor College of Medicine and Texas Children’s Hospital in Houston, and Sarah S. Long, MD, of Drexel University in Philadelphia, in a commentary accompanying the study.

Thus there is a need for more research on the deployment and safety of maternal flu vaccination globally, especially in low- and middle-income countries, they noted.

Other issues Munoz and Long had with the study was the relatively short follow-up period of 1 to 5 years in vaccine-exposed children, and the fact that the majority of evaluated studies were for the 2009 H1N1 pandemic vaccine, which demonstrated “missed opportunities for the assessment of safety of seasonal vaccines.”

Still, the data from Foo and co-authors are “robust…these findings should lead providers to offer influenza vaccines to pregnant women confidently, factually, and in a manner that presumes rather than queries their acceptance of the recommendation,” Munoz and Long concluded.

Foo and co-authors reviewed the literature on early childhood (age <5 years) health associated with exposure to flu vaccines in utero until July 2019. Their search resulted in 3,647 records, of which nine met the inclusion criteria:

  • Presence of any mother-child pair population that reported exposure to flu vaccines in utero (pandemic or seasonal).
  • Presence of an unexposed mother-child pair control group.
  • Investigation of at least one health outcome in children, ages 6 months to 5 years.

“Studies examined infectious, atopic, autoimmune, and neurodevelopmental outcomes, and all-cause morbidity and mortality,” they stated.

Non-English language studies, case studies, and research letters made up some of the exclusion criteria, and some studies were rejected because they did not contain a measurement of flu vaccination during pregnancy or did not report the outcome measure of early childhood health.

“Of the 9 included studies, methodology and study outcomes were highly diverse,” the authors reported. For instance, vaccination status during pregnancy was by self-report in one study and written or electronic health records in three studies.

Among half a dozen studies on the 2009 monovalent pandemic influenza A virus subtype H1N1 (A/H1N1) vaccines, four only looked at adjuvanted vaccines, according to Foo’s group.

Also, outcomes were far reaching, including eight different types of infections or infectious conditions, 11 types of autoimmune conditions, and eight kinds of neurodevelopmental conditions. Outcomes for all-cause morbidity ranged from 1-year all-cause hospitalization to “5-year all-cause hospitalization, urgent and inpatient health services used, and pediatric complex chronic conditions.”

“Given the small number of studies in which similarly defined outcomes were addressed, meta-analyses were deemed not possible,” the authors explained.

They also identified several potential confounders in the nine studies, such as maternal age, ethnicity, place of birth, marital status, use of antenatal care, and the child’s ethnicity.

The authors reported that, for pediatric mortality, “No significant associations were identified in the 2 studies that examined mortality as an outcome.”

Finally, for ASD, one 2017 study found a slightly elevated risk, which did not hold up after adjustment for multiplicity, while another from the same year “found no significant association between [influenza vaccines] exposure in utero and autism spectrum disorder,” according to Foo’s group. Unfounded fears of causality between the flu vaccine and ASD has become a tenet in the anti-vaxxer movement.

  1. A review of a small number of studies that examined outcomes in children older than 6 months of age did not identify an association between exposure to influenza vaccines in utero and adverse childhood health outcomes.

  2. One reviewed study found a slightly elevated risk for autism spectrum disorder (ASD), which did not hold up after adjustment for multiplicity, while another reported no significant association between influenza vaccines exposure in utero and ASD.

Shalmali Pal, Contributing Writer, BreakingMED™

Foo reported support from a Curtin University Postgraduate Award, a postgraduate top-up scholarship from the Wesfarmers Centre of Vaccines and Infectious Diseases, and Telethon Kids Institute. Co-authors reported support from the National Health and Medical Research Council.

Munoz and Long reported no relationships relevant to the contents of this paper to disclose.

Cat ID: 191

Topic ID: 83,191,730,30,191,41,44,192,561,925