Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring : A Cohort Study

Ann Intern Med. 2020 Oct 20;173(8):597-604. doi: 10.7326/M20-0167. Epub 2020 Sep 1.

Abstract

Background: There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD).

Objective: To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 ("swine flu") during pregnancy.

Design: Population-based cohort study using nationwide registers.

Setting: Seven health care regions in Sweden.

Participants: Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed.

Measurements: Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD).

Results: Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, -0.09% to 0.17%) for ASD and 0.02% (CI, -0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD).

Limitation: Data on H1N1 influenza infection are lacking.

Conclusion: This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring.

Primary funding source: Swedish Research Council.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder / epidemiology*
  • Autistic Disorder / epidemiology
  • Female
  • Humans
  • Incidence
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza, Human / prevention & control*
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control*
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects
  • Retrospective Studies
  • Risk Factors
  • Sweden / epidemiology

Substances

  • Influenza Vaccines