Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis
Idro R., Gwer S., Williams TN., Otieno T., Uyoga S., Fegan G., Kager PA., Maitland K., Kirkham F., Neville BGR., Newton CRJ.
BACKGROUND: There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area. METHODS: We recruited 133 children, aged 3-156 months, who presented to a district hospital on the Kenyan coast with acute seizures and frequency-matched these to children of similar ages but without seizures. We defined iron deficiency according to the presence of malarial infection and evidence of inflammation. In patients with malaria, we defined iron deficiency as plasma ferritin<30 µg/ml if plasma C-reactive protein (CRP) was<50 mg/ml or ferritin<273 µg/ml if CRP≥50 mg/ml, and in those without malaria, as ferritin<12 µg/ml if CRP<10 mg/ml or ferritin<30 µg/ml if CRP≥10 mg/ml. In addition, we performed a meta-analysis of case-control studies published in English between January 1966 and December 2009 and available through PUBMED that have examined the relationship between iron deficiency and febrile seizures in children. RESULTS: In our Kenyan case control study, cases and controls were similar, except more cases reported past seizures. Malaria was associated with two-thirds of all seizures. Eighty one (30.5%) children had iron deficiency. Iron deficiency was neither associated with an increased risk of acute seizures (45/133[33.8%] cases were iron deficient compared to 36/133[27.1%] controls, p = 0.230) nor status epilepticus and it did not affect seizure semiology. Similar results were obtained when children with malaria, known to cause acute symptomatic seizures in addition to febrile seizures were excluded. However, in a meta-analysis that combined all eight case-control studies that have examined the association between iron deficiency and acute/febrile seizures to-date, iron deficiency, described in 310/1,018(30.5%) cases and in 230/1,049(21.9%) controls, was associated with a significantly increased risk of seizures, weighted OR 1.79(95%CI 1.03-3.09). CONCLUSIONS: Iron deficiency is not associated with an increased risk of all acute seizures in children but of febrile seizures. Further studies should examine mechanisms involved and the implications for public health.