Does iron deficiency raise the seizure threshold?

To determine the effect of iron status on the seizure threshold, measures of iron sufficiency were prospectively evaluated in 51 children presenting to a pediatric emergency department with a febrile illness with (26) or without (25) an associated febrile seizure. A higher proportion of children from the febrile seizure group had a family history of mental retardation (5/26 versus 0/25, P = .02) or of previous febrile seizures (10/26 versus 2/23, P = .01). The two groups were otherwise comparable for age, sex, race, family history of afebrile seizures, temperature at presentation, white blood cell count, differential, and vitamin and antibiotic use. Patients with febrile seizures were less frequently iron deficient as defined by a free erythrocyte protoporphyrin level above 0.80 ng/L (2/23 versus 10/25, P < .01), hemoglobin concentration less than 110 g/L (1/26 versus 6/25, P < .03), hematocrit less than 0.30 L/L (0/22 versus 4/25, P < .02), mean corpuscular hemoglobin less than 20 pg (0/25 versus 3/24, P < .04), mean corpuscular volume less than 65 fL (0/26 versus 4/24, P < .02), and platelet count higher than 550 x 10(9)/L (0/26 versus 3/25, P < .04). This association was even stronger when adjusted for differences in family history. None of the patients in the febrile seizure group was being treated for iron deficiency at presentation, whereas three of 25 controls used an iron supplement (P < .04). Iron deficiency may protect against the development of febrile seizures.