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Abstract
Objective To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood.
Design Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates.
Setting Population-based.
Participants 1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario).
Exposure Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy.
Main outcome measures We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes ‘epilepsy’ and ‘febrile seizures’.
Results Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester.
Conclusions In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.
- epidemiology
- neurology
Data availability statement
Data may be obtained from a third party and are not publicly available. The Ontario dataset from this study was linked using unique encoded identifiers and analysed at ICES, where they are held securely in coded form. While data sharing agreements prohibit ICES from making the dataset publicly available, access may be granted to those who meet prespecified criteria for confidential access, available at www.ices.on.ca/DAS. The full dataset creation plan and underlying analytical code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are, therefore, either inaccessible or may require modification. The NSW dataset is stored securely at the Curtin University School of Public Health and access is restricted to named investigators in Australia. The Norwegian dataset contains personal data and cannot be made public due to confidentiality requirements according to Norwegian legislation. However, researchers who are interested in analysing data from the registries used in this study may apply to the appropriate registry owners after having obtained all necessary approvals according to Norwegian legislation.