Influenza Infection During Pregnancy and Risk of Seizures in Offspring

Abstract

Importance: Seizure is a common neurological problem among infants and children up to age 6 years. Prenatal exposure to maternal influenza infection has been reported to be associated with childhood seizures.

Objective: To evaluate the association between maternal influenza infection and risk of childhood seizures.

Designs, setting, and participants: This cohort study identified mother-offspring pairs from January 1, 2004, to December 31, 2013, using records in Taiwan's Maternal and Child Health Database. Mothers who had influenza infection during pregnancy and their first offspring were identified and assigned to the influenza group. Mothers in the control group were those without influenza during pregnancy and were matched 1:4 with mothers in the influenza group by maternal age, offspring sex, and date of delivery. Offspring were followed up until December 31, 2020. Data were analyzed between March 2023 and July 2024.

Exposure: Diagnosis of influenza infection during pregnancy defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes 487.0, 487.1, and 487.8, or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes J09, J10, and J11.

Main outcomes and measures: The primary outcome was the association between maternal influenza infection during pregnancy and risk of any type of seizures during childhood, including both epilepsy and febrile seizures. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression models. Pregnancy-related complications were collected as covariates.

Results: A total of 1 316 107 mother-offspring pairs were enrolled, of whom 75 835 mothers (predominant maternal age, 25-29 years; 39 324 male offspring [51.9%]) were assigned to the influenza group and 1 240 272 were matched and assigned to the control group (n = 303 340; predominant maternal age, 30-34 years; 157 296 male offspring [51.9%]). In the influenza group, there was a slightly higher prevalence of placenta previa or abruption compared with the control group (1.6% [1241] vs 1.4% [4350]; P < .001). The cumulative risk of seizures was higher among offspring whose mothers had influenza infection. After controlling for potential confounders, the AHRs were 1.09 (95% CI, 1.05-1.14) for seizures, 1.11 (95% CI, 1.06-1.17) for febrile convulsions, and 1.04 (95% CI, 0.97-1.13) for epilepsy. In the subgroup analysis, no statistically significant differences were observed between the trimesters regarding the timing of influenza infection.

Conclusions and relevance: Results of this cohort study suggest that maternal influenza infection during pregnancy was associated with an increased risk of childhood seizures, especially febrile seizures, but not epilepsy. Further studies are needed to elucidate the mechanisms underlying childhood neurological development.

Figure 1.. Composition of the Study Cohort

Figure 2.. Cumulative Risks of Seizures, Febrile Convulsions, and Epilepsy in the Influenza vs Control Group

The risks of seizures and febrile convulsions were higher in offspring in the influenza group, while the risk of epilepsy did not follow a similar pattern.