For healthcare professionals only


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

BMJ 1996; 313 doi: (Published 10 August 1996) Cite this as: BMJ 1996;313:343
  1. Alfredo Pisacane, senior lecturera,
  2. Renato Sansone, postgraduate traineea,
  3. Nicola Impagliazzo, postgraduate traineea,
  4. Angelo Coppola, postgraduate traineea,
  5. Paolo Rolando, paediatric consultantb,
  6. Alfonso D'Apuzzo, paediatricianb,
  7. Ciro Tregrossi, paediatricianb
  1. a Dipartimento di Pediatria, Universita di Napoli, Via Pansini 5, 80131 Naples, Italy
  2. b Divisione di Pediatria, Ospedale di Castellammare di Stabia, Naples
  1. Correspondence to: Dr Pisacane.
  • Accepted 24 April 1996

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)

View this table:


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. 1.
  2. 2.
  3. 3.
  4. 4.
  5. 5.
View Abstract