A new study published in the Annals of Internal Medicine refutes any association between the AS03-adjuvanted influenza A/H1N1pdm09 vaccine (Pandemrix, GlaxoSmithKline) given to pregnant women and an increased risk for autism spectrum disorder (ASD) diagnosis in children.1

In this population-based cohort study using Swedish register data, researchers from Karolinska Institutet linked vaccination data in pregnant women from 7 Swedish healthcare regions in 2009-2010 to the Swedish Medical Birth Register and the Swedish National Patient Register to identify risk for ASD in the offspring (primary outcome) and autistic disorder (AD), the most severe form of ASD (secondary outcome). Children were followed from the date of birth until first diagnosis of ASD, death, or the end of follow-up (December 31, 2016), whichever came first.

In total, 39,726 infants were prenatally exposed to the H1N1 vaccine (13,845 during the first trimester) and 29,293 infants were unexposed. Mean length of follow-up was 6.7 years in both exposed and unexposed children. Incidence rates of ASD and AD were similar throughout the study period and between the study regions. During follow-up, 394 (1%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD.

After adjustment for potential confounders, H1N1 vaccine exposure during fetal life was not associated with a later childhood diagnosis of ASD (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.81-1.12) or AD (aHR, 0.96; 95% CI, 0.80-1.16). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (95% CI, -0.09% to 0.17%) for ASD and 0.02% (95% CI, -0.09% to 0.14%) for AD.

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Restricting the analysis to vaccination in the first trimester (first 14 weeks) yielded similar results for both ASD (aHR, 0.92; 95% CI, 0.74-1.16) and AD (aHR, 0.91; 95% CI, 0.70-1.18).

Risk estimates did not change when researchers performed 4 sensitivity analyses for ASD. After exclusion of individuals in the 3 counties where vaccination data were incomplete, the aHR was 0.95 (95% CI, 0.80-1.12). When the outcome definition was restricted to primary diagnoses alone, the aHR was 0.94 (95% CI, 0.79-1.12). After follow-up was truncated at 6 years of age, the aHR was 0.97 (95% CI, 0.81-1.16). In a post hoc analysis restricted to offspring of mothers born in Sweden, the aHR was 0.89 (95% CI, 0.72-1.09). The HRs were similar for AD.

Researchers listed several key limitations. They could not rule out confounding due to absence of paternal characteristics. Also, they did not have access to data on seasonal influenza vaccinations or other non-H1N1 vaccinations during or beyond the study period. Finally, results may not be applicable to nonadjuvanted influenza vaccines, since the H1N1 vaccine investigated in this study is an adjuvanted vaccine that is no longer in use.

Nonetheless, this study “is a rare and welcome contribution to a more comprehensive safety evaluation, which goes significantly beyond the perinatal period,” stated Anders Hviid, MSc, DrMedSci, of the Statens Serum Institut and University of Copenhagen in Denmark, in an accompanying editorial.2

“Our null findings are important since some people have suspected that vaccinations could cause autism, and the anti-vaccine movement seems to be growing in the Western world,” said lead study author, Jonas F Ludvigsson, MD, PhD, in a press release.3 “H1N1 vaccination has previously been linked to an increased risk of narcolepsy in young people, but vaccinating pregnant women does not seem to influence the risk of ASD in the offspring,”

Dr. Ludvigsson added, “Vaccination research has never been more important. Anticipating a vaccine against COVID-19, millions of pregnant women are likely to be offered such a vaccination. While our research group did not study COVID-19 vaccine effects, our research on H1N1 vaccination adds to the current knowledge about vaccines, pregnancy and offspring disease in general.”


1. Ludvigsson JF, Winell H, Sandin S, Cnattingius S, Stephansson O, Pasternak B. Maternal influenza A(H1N1) immunization during pregnancy and risk for autism spectrum disorder in offspring: a cohort study [published online September 1, 2020]. Ann Intern Med. doi: 10.7326/M20-0167

2. Hviid A. Vaccine safety in pregnancy: going beyond the perinatal period [published online September 1, 2020]. Ann Intern Med. doi: 10.7326/M20-5489

3. Swine flu vaccination in pregnant women did not increase risk of autism in offspring [news release]. Stockholm, Sweden: Karolinska Institutet. Published September 1, 2020. https://news.ki.se/swine-flu-vaccination-in-pregnant-women-did-not-increase-risk-of-autism-in-offspring. Accessed September 7, 2020.