Indian Pediatr 2012;49: 17-19
Iron Deficiency as a Risk Factor for Simple
Febrile Seizures– A Case Control Study
P Leela Kumari, MKC Nair, SM Nair, Lalitha Kailas*
and S Geetha
From Clinical Epidemiology Resource and Training Centre (CERTC),
and *Department of Paediatrics, Medical College, Thiruvananthapuram,
Correspondence to: Dr Leela Kumari P, Assistant Professor
of Pediatrics, SAT Hospital, Medical College, Thiruvananthapuram, Kerala,
Received: September 24, 2010;
Initial review: October 25,
Accepted: January 11, 2011.
Published online: 2011, May 30.
Objective: To study the role of iron deficiency as a risk factor for
simple febrile seizures.
Design: Case control study.
Setting: Pediatric department of a tertiary care
Participants: 154 cases and 154 controls were
included in the study. Consecutive cases and concurrent controls were
selected. Cases were children of age group 6 months to 3 years presenting
with simple febrile seizures. Controls were children of same age group
presenting with short febrile illness but without any seizures.
Methods: After informed consent, detailed history
was taken and clinical examination done in both cases and controls and
blood investigations were done to diagnose iron-deficiency in both cases
and controls. Iron deficiency was diagnosed as per WHO criteria
(hemoglobin value <11g%, red cell distribution width of >15% and serum
ferritin value < 12ng/mL). Other explanatory variables, which can be the
potential confounders were also included in the study and considered for
Results: Highly significant association was found
between iron deficiency and simple febrile seizures in both univariate and
multivariate analysis. Crude odds ratio was 5.34 (CI 3.27- 8.73, P<0.001)
and adjusted odds ratio in the logistic regression analysis was 4.5 (CI
2.69- 7.53, P <0.001).
Conclusions: Iron deficiency is a significant risk
factor for simple febrile seizures in children of age group 6 months to 3
Key words: Febrile seizures, Hemoglobin, India, Iron deficiency,
Febrile seizure episodes are agonizing to the parent and
child and can cause psychological trauma to both . Iron deficiency is
the commonest micronutrient deficiency worldwide, and is a preventable and
treatable condition . Iron is needed for brain energy metabolism, for
metabolism of neurotransmitters and for myelination. Thus, iron deficiency
may alter the seizure threshold of a child
[8,9]. Iron deficiency is postulated as a risk factor for
febrile seizures in children and it is an easily correctable condition
[10,11]. We, therefore, studied the association between iron deficiency
and simple febrile seizures.
Febrile seizures are the
commonest cause of
seizures in children, occuring in 2-5% of children
. Complications like aspiration can occur
during each episode of seizures [2-5].
This case control study was done in the Department of
Pediatrics, SAT Hospital, Thiruvananthapuram during August 2009 to
February 2010. Ethical clearance was obtained for the study from the
Ethical committee, Medical College, Thiruvananthapuram. Cases were
children of age group 6 months to 3 years presenting with simple febrile
seizures to the Pediatrics Emergency Department and wards of the hospital
during the study period. Diagnostic criteria for simple febrile seizures
(based on AAP Clinical Practice Guidelines) included seizures associated
with fever and the seizures were generalized, short duration (less than 15
minutes), no recurrence of seizures within 24 hours, child is otherwise
neurologically healthy and without any neurological abnormality before and
after the episode of seizures, with age group between 6 months to 5 years
. Consecutive cases were selected for the study and concurrent controls
were selected from the same setting and included febrile children of age
group 6 months to 3 years who presented with short duration fever (<3
days) but without seizures. Cases and controls were selected in 1:1 ratio.
No matching was done. Children presenting with atypical febrile seizures,
afebrile seizures, those having any signs of central nervous system
infection, those with any chronic neurodevelopment problems, those who
were previously diagnosed cases of other hematologic problems like
hemolytic anemias, bleeding or coagulation disorders, haematologic
malignancy, those who were on iron supplementation, and very sick children
were excluded from the study.
After informed consent, detailed history was elicited
and physical examination was done. Hospital records were also examined for
relevant data. Blood investigations done to diagnose iron deficiency
included hemoglobin estimation and red cell distribution width (RDW) using
an automated hematology analyzer (Sysmex Kx -21) and serum ferritin
estimation using ELISA method (Acubind ELISA). Iron deficiency was
diagnosed by hematologic investigations of hemoglobin value <11g%, serum
ferritin value <12 ng/mL and RDW > 15% (WHO) . Other variables studied
included age of the child, sex, socioeconomic status, family history of
febrile seizure in first degree relatives, family history of epilepsy in
first degree relatives, consanguinity, neonatal hospital admissions (NICU
or special care nursery admissions), daycare attendance for more than one
month, prematurity (<37 weeks gestational), protein energy malnutrition (IAP
classification), immunization status of child, and Hib vaccine status.
Sample size was calculated using Epi Info program based
on the assumptions that alpha error 5%, beta error 20% i.e. power of study
80%, Odds ratio 2, and prevalence of exposure (iron deficiency) in the
non-ill group (controls) 30% (obtained from a pilot study) provided a
value of 153 children in each group. Data were entered in MS Excel,
cleaned and completeness checked. Analysis was done using SPSS Version 11.
Analysis includes univariate analysis for crude odds ratio and confidence
interval, bivariate analysis for confounding and interaction and
multivariate analysis for adjusted odds ratio.
154 cases and 154 controls were included in the study.
The average age of cases and controls was 17.5±8.81 and 17.6±8.54 months,
respectively. Variables found to be significantly associated with simple
febrile seizures on univariate analysis included iron deficiency, family
history of febrile seizures in first degree relatives, family history of
epilepsy in first degree relatives, daycare attendance, and prematurity (Table
I). Significant variables were considered for multivariate analysis.
Variables found to be significant in multivariate analysis included iron
deficiency (adjusted odds ratio 4.5, 95% CI 2.69- 7.53, P=0.001),
family history of febrile seizures in first degree relatives (adjusted
odds ratio 2.44, 95%CI 1.26- 4.73, P=0.008), family history of
epilepsy in first degree relatives (adjusted odds ratio 2.21, 95% CI
1.11-4.38, P value 0.02), daycare attendance (adjusted odds ratio
2.80, 95% CI 1.29- 6.06, P= 0.009), and prematurity (adjusted odds
ratio 2.58, 95% CI 1.19-5.62, P=0.01).
TABLE I Relation of Various Study Variable with Simple Febrile Seizures in Children Between 6 mo and 3 y
||Crude Odds Ratio (CI)
H/O febrile seizure
Immunized for age
H/o: history of; NICU: Neonatal Intensive Care Unit.
Iron deficiency was found as a significant risk factor
for simple febrile seizures in children of age group 6 months to 3 years
in our study. In the study done by Pisacane, et al. , among
children of the same age group, similar results were noted and the odds
ratio was 3.3 (95% CI of 1.7-6.5). Iron status was measured by hemoglobin,
MCV and serum iron in that study. Dawn, et al.  also found
similar results with children with febrile seizures almost twice likely to
have iron deficiency compared to controls.
In the study by Daoud, et al. , the
significance of iron status as a possible risk factor was evaluated. The
mean serum ferritin level in the cases was 29.5 mcg/L, much lower than the
values in the controls (53.5 mcg/L). Similar observations were made in a
study done by Vaswani, et al.  from Mumbai. The mean serum
ferritin level was significantly low in children with first febrile
seizures (31.9±31.0 mcg/L) as compared to controls (53.9±56.5 mcg/L) (P=0.003).
However, no significant difference was noted in the mean hemoglobin value
of cases (9.4±1.2 g/dL) and controls (9.5±1.0 g/dL) (P=0.7), or in
the mean value of blood indices. In our study, iron deficiency was
diagnosed by three criteria i.e. hemoglobin, red cell distribution
width, serum ferritin, and all three parameters were significantly
different among cases and controls.
The strength of our study included standardized
criteria for diagnosing febrile seizures, and iron deficiency, elimination
of incidence prevalence bias, concurrent enrollment of controls and cases,
and no recall bias regarding exposure. The study does have some
limitations. As it was a hospital-based study the prevalence of exposure
and outcome variables may be different from a community setting. Serum
ferritin, a nonspecific acute phase reactant can rise in any inflammatory
conditions, although both cases and controls were having fever at the time
of enrollment. Iron deficiency and lead poisoning may be associated. Blood
lead levels could not be determined in our subjects.
We report iron deficiency as a modifiable risk factor
for simple febrile seizures in Indian children of age group 6 months to 3
years. Early detection and timely correction of iron deficiency may be
helpful for prevention of simple febrile seizures in children of this age
Contributors: PLK collected, analyzed and
interpreted the data, performed literature review and drafted the
manuscript. MKCN designed the study, supervised data collection and
analysis, reviewed and approved the final manuscript. SMN assisted in data
analysis. LK was the pediatrician in charge of study participants and
supervised data collection, SG assisted in data collection and analysis.
Funding: None; Competing Interest: None
What This Study Adds?
• Iron deficiency is a significant risk factor for simple febrile
seizures in children 6 mo - 3 y age.
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