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OP03 Is in-utero exposure to maternal h1n1 influenza infection and vaccination associated with an increased risk of childhood seizures? a norwegian registry-based study
  1. L Oakley1,
  2. IJ Bakken2,
  3. SE Håberg2
  1. 1Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  2. 2Department of Children’s Health, Norwegian Institute of Public Health, Oslo, Norway


Background Previous studies have suggested that in-utero exposure to infection is associated with an increased risk of childhood seizures, but there is a lack of evidence regarding in-utero exposure to influenza. The objective of this study was to investigate whether in-utero exposure to the H1N1 pandemic, influenza infection, or vaccination is associated with a higher risk of childhood seizures.

Methods Registry-based study including all children born in Norway between 01/10/2009 and 31/12/2015 (n=254,347). Data were linked from sources including the Medical Birth Registry, the Norwegian Immunisation Register, the primary care reimbursement system, and the Norwegian Patient Registry. We investigated three exposures: 1) in-utero exposure to the H1N1 pandemic (≥1 pregnancy day during the main H1N1 pandemic wave), 2) in-utero exposure to maternal influenza infection (diagnosis of influenza-like illness in primary care, and/or laboratory confirmed H1N1 infection), and 3) in-utero exposure to H1N1 vaccination. We used Cox Proportional Hazards modelling to compare the incidence of seizures (any seizure, febrile seizure, epilepsy) according to exposure status from birth until 31/12/2015. Hazard ratios were adjusted for parity, maternal age, multiplicity, sex and maternal smoking.

Results 24.4% (62,032) children were exposed in-utero to the H1N1 pandemic, of whom 3.7% (2,299) were exposed in-utero to maternal influenza. Among 77 671 children with ≥1 in-utero day during the vaccination period, 34.9% (n=27,138) were exposed to vaccination. The risk of febrile seizures was slightly increased after in-utero exposure to the pandemic (aHR 1.06, 95% CI 1.00–1.12), but there was no evidence of an increased risk of epilepsy (aHR 1.08, 95% CI 0.93–1.26). There was no evidence of an overall association between in–utero exposure to maternal H1N1 infection and childhood seizures (febrile seizures aHR 1.17, 95% CI 0.92–1.49; epilepsy aHR 0.93, 95% CI 0.50–1.75). However, when stratified by trimester of exposure we observed a 40% increased risk of febrile seizures after infection during the second trimester (aHR 1.42, 95% CI 1.02–1.99). In-utero exposure to vaccination was not associated with an increased risk of childhood seizures.

Discussion This large study benefits from virtually no loss to follow-up and mandatory vaccination reporting. The limitations includes our inability to validate outcome data, and the under-reporting of influenza infection.Our finding of no increased risk subsequent to in-utero exposure to H1N1 vaccination supports the safety of vaccination in pregnancy. Although we found no overall evidence that in-utero exposure to maternal H1N1 infection was associated with febrile seizures, a small increased risk of febrile seizures after second trimester exposure warrants further investigation.

  • pregnancy
  • influenza
  • febrile seizures

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