Register-based studies on febrile seizures in Denmark.

During a short period of brain development, one out of 25 children experience seizures when exposed to fever. The risk and consequences of these febrile seizures remain incompletely understood. We have conducted a number of studies within a population-based cohort of 1.6 million children born in Denmark (1977-2004). We constructed the cohort by linking registers on civil service, health, and cause of death. We followed the cohort for up to 28 years with virtually no loss to follow-up. The aetiology of febrile seizures depends on a genetic susceptibility that can be transmitted through both parents. The risk of febrile seizures increases with decreasing birth weight and gestational age at birth indicating that pre- and perinatal risk factors play a causal role. Measles, mumps, and rubella vaccination increases the risk of febrile seizures for two weeks, but the absolute risk is small even in high-risk children. Febrile seizure is associated with an increased risk of epilepsy and the risk remained high well into adulthood. The risk of epilepsy is particular high for persons with cerebral palsy, low Apgar scores, or a family history of epilepsy. The risk of schizophrenia is slightly increased among persons with a history of febrile seizures even in persons without epilepsy, but the association need not be causal and more studies are needed. Febrile seizure is a common condition with a benign outcome for the vast majority of children. Genes and environmental factors operating in early life seem to play a causal role.