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Iron deficiency anaemia and febrile convulsions: case-control study in children under 2 years

^a Dipartimento di Pediatria, Universita di Napoli, Via Pansini 5, 80131 Naples, Italy, ^b Divisione di Pediatria, Ospedale di Castellammare di Stabia, Naples

Correspondence to: Dr Pisacane.

Febrile convulsions are the most common type of seizure and occur in 2-4% of all children.¹ A family history of convulsions; maternal smoking; and alcohol consumption during pregnancy have been associated with febrile seizures,^{2 3} but the risk factors remain largely unknown.

Iron is involved in the metabolism of several neurotransmitters, and monoamine and aldehyde oxidase are reduced in iron deficiency anaemia⁴, which is common during the second and the third year of life and has been associated with behavioural and development disturbances.⁵ Thus we investigated the association between iron deficiency anaemia and febrile seizures by a case-control study.

Patients, methods, and results

All 156 children aged 6-24 months admitted to Castellammare di Stabia Hospital, Naples, between 1 January 1993 and 30 June 1995 with diagnosis of febrile convulsions were enrolled in the study. They were healthy children without previous afebrile seizures or central nervous system disease. A febrile convulsion was defined as a seizure that occurred while the child had a rectal temperature of at least 38.3°C or an axillary temperature of at least 37.8°C documented either in the emergency department or in the history. Two groups of controls were selected: a random sample of children admitted to the same ward with diagnosis of respiratory and gastrointestinal infection during that period, and a group of healthy children randomly selected from the provincial birth register for an iron deficiency survey in Greater Naples during 1994.

Routine haematological investigations were performed for hospitalised patients at hospital admission and for population controls at the Department of Paediatrics of Naples. Data were collected from clinical records by two medical students unaware of the study hypothesis.

Iron deficiency anaemia was defined as the presence of haemoglobin concentration <105 g/l, mean corpuscular volume <70 fl, and serum iron concentration of <5.4 µmol/l. In our population of this age group the prevalence of anaemia is about 10%; we assumed that a prevalence of 20-25% among cases would be clinically relevant. Relative risk was calculated by odds ratio and 95% confidence interval by Cornfield's method.

No differences in distribution of gender, maternal age and education, birth weight and type of birth were found among study groups. Mean age was 15 (SD 5.6) months for cases, 12.4 (5) months for hospital controls, and 13 (2) months for population controls. Anaemia was significantly more common in cases (30%) than hospital (14%) and population (12%) controls (table 1).

Table 1--Haemoglobin concentrations in children with febrile seizures and controls. Values are numbers (percentages)
------------------------------------------------------------------------------------------------------------------------
                                                Hospital controls                        Population controls
------------------------------------------------------------------------------------------------------------------------
                       No (%)                                 Odds ratio                               Odds ratio
Haemoglobin          of cases              No (%)          (95% confidence            No (%)        (95% confidence
concentration (g/l)  (n = 146)            (n = 146)            interval)             (n = 147)          interval)
------------------------------------------------------------------------------------------------------------------------
>/=105                102 (70)             125 (86)          1                       130 (88.4)       1
<105                   44 (30)              21 (14)          2.6 (1.4 to 4.8)         17 (11.6)       3.3 (1.7 to 6.5)

Comment

The association between iron deficiency anaemia and febrile seizures has not been described before, and chance or unknown confounding are possible explanations. None the less, selection bias as well as confounding by social class do not seem likely in this study.

Fever can worsen the negative effects of anaemia or of iron deficiency on the brain and a seizure can occur as a consequence. Alternatively, anaemia can be associated with the severity of a febrile illness, and more severe cases could be more likely to get seizures. None the less, febrile seizures usually occur early in the illness, before haemoglobin concentration has a chance to drop as a result of infection.

Funding: Departimento di Pediatria, Universita di Napoli Federico II.

Conflict of interest: None.

1. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from birth. I. Prevalence and recurrence in the first five years of life. BMJ 1985;290:1307-10.
2. Nelson KB, Ellenberg JH. Prenatal and perinatal antecedents of febrile seizures. Ann Neurol 1990;27:127-31. [Medline]
3. Cassano PA, Koepsell TD, Farwell JR. Risk of febrile seizures in childhood in relation to prenatal maternal cigarette smoking and alcohol intake. Am J Epidemiol 1990;132:462-73. [Abstract/Free Full Text]
4. Parks YA, Wharton BA. Iron deficiency and the brain. Acta Paediatr Scand 1989;55(suppl 361):71-7.
5. Walter T, De Andraca I, Chadud P, Perales CG. Iron deficiency anemia: adverse effects on infant psychomotor development. Pediatrics 1989;84:7-17. [Abstract/Free Full Text]

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