Iron deficiency as a risk factor for simple febrile seizures--a case control study.
ABSTRACT To study the role of iron deficiency as a risk factor for simple febrile seizures.
Case control study.
Pediatric department of a tertiary care teaching hospital.
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.
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 <11 g%, red cell distribution width of >15% and serum ferritin value <12 ng/mL). Other explanatory variables, which can be the potential confounders were also included in the study and considered for analysis.
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).
Iron deficiency is a significant risk factor for simple febrile seizures in children of age group 6 months to 3 years.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Febrile seizure is one of the most common neurological conditions of childhood. Several theories, such as iron deficiency anemia have been proposed as the pathogenesis of this condition. The aim of this study was to find the association between iron deficiency anemia and febrile seizures in children aged 6 months to 3 years admitted in Valie Asr hospital in Zanjan. Hemoglobin (Hb), mean corpuscular volume (MCV), serum iron (SI), total iron binding capacity (TIBC) and SI/TIBC ratio were assessed in one hundred children with febrile seizures and compared to the values of one hundred healthy children presenting in a heath care center in the same period as the control group. A total of 6% of cases had iron deficiency anemia which was similar to the control group. In the case group SI/TIBC ratio below 12% was seen in 58% of children which was significantly higher than that of the control group (29%). The results of this study suggest that although anemia was not common among febrile seizure patients, iron deficiency was more frequent in these patients.Iranian journal of child neurology. 01/2012; 6(4):27-31.
- [Show abstract] [Hide abstract]
ABSTRACT: Febrile seizure (FS) is the most common childhood seizures which occur in 2-5% of children. Studies about association between iron deficiency and febrile seizure have shown contradictory results. The purpose of this study was to compare the iron status of children with first febrile seizure and healthy control group. In an analytic case-control study , iron status of 6 to 60 months old admitted children with first FS to Shahid Sadoughi Hospital from December 2011 to August 2012 was evaluated and compared with healthy age and sex matched control children whom were referred for routine health care to primary health care center of Azadshar Yazd, Iran. Forty five (44%) girls and 55 boys with a mean age of 23.7 ± 14.3 months were evaluated. In children with FS , hemoglobin level (11.46 ± 1.18 g/dl vs. 11.9 ± 0.89 g/dl, p= 0.042) , serum iron levels (48.91 ± 22.96 μg/dl vs. 75.13 ± 35.57 μg/dl , p= 0.001) and serum ferritin level (38.52 ± 11.38 ng/ml vs. 54.32 ± 13.46 ng/ml, p= 0.001) were lower than in healthy children group . Iron deficiency (48% vs. 28% , odds ratio 4.3, p=0.03) and iron deficiency anemia (22% vs. 10% , odds ratio = 3.16, p= 0.04) were more frequent in children with FS. Based on the result of this study, iron deficiency could be an important risk factor for development of febrile convulsion. Evaluation of iron status is encouraged to be performed in children with febrile seizure.Iranian journal of pediatric hematology and oncology. 01/2013; 3(1):200-3.
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.
ebrile 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]. Febrile
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
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, Kerala, India.
Correspondence to: Dr Leela Kumari P, Assistant Professor of Pediatrics, SAT Hospital, Medical College, Thiruvananthapuram,
Kerala, India. firstname.lastname@example.org
Received: September 24, 2010; Initial review: October 25, 2010; Accepted: January 11, 2011.
17VOLUME 49__JANUARY 16, 2012
Published online: 2011, May 30. PII: S09747559INPE10000285-1
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 teaching
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 analysis.
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
Conclusions: Iron deficiency is a significant risk factor for
simple febrile seizures in children of age group 6 months
to 3 years.
Key words: Febrile seizures, Hemoglobin, India, Iron
R R R R R E E E E E S S S S S E E E E E A A A A A R R R R R C C C C C H P H P
H PH P
H P A A A A A P P P P P E E E E E R R R R R
Accompanying Editorial: Page 13-14
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
LEELA KUMARI, et al.
IRON DEFICIENCY AND FEBRILE SEIZURES
18VOLUME 49__JANUARY 16, 2012
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
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
Cases (n=154) Controls (n=154)Crude Odds Ratio (CI) P value
Age 17 mo
86(55.8%) 87(56.5%) 1.027 (0.6551.610) 0.909
Social Class 4 115(74.7%)109(70.8%)1.217 (0.737-2.01) 0.443
Full Term 124(80.5%)142(92.2%) 2.86 (1.41-5.83)0.003
NICU admission46 (29.9%) 37 (24%) 1.35 (0.81-2.23) 0.248
Family H/O febrile seizure40 (26%)20 (13%)2.35 (1.30-4.25) 0.004
Family H/O epilepsy36 (23.4%)17 (11%) 2.46 (1.31-4.60)0.004
Daycare attendance32 (20.8%)12 (7.8%) 3.1 (1.53-6.29)0.001
Not Immunized for age29(18.8%)27(17.5%) 1.09 (0.61-1.99)0.768
No Hib vaccine 110(71.4%) 105(68.2%)1.17 (0.72-1.89) 0.535
Iron deficiency98 (63.6%) 38 (24.7%) 5.34 (3.27-8.73) 0.001
Malnutrition62 (40.3%) 52(33.8%) 1.32 102(66.2%)0.238
H/o: history of; NICU: Neonatal Intensive Care Unit.
19VOLUME 49__JANUARY 16, 2012
LEELA KUMARI, et al.
IRON DEFICIENCY AND FEBRILE SEIZURES
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 stated.
1. Johnston MV. Seizures in childhood. In: Kleigman RM,
Behrman RE,Jenson HB, Stanton BP. Nelson Text Book of
Pediatrics 18th Edition Philadelphia: Saunders Elsevier;
2. American Academy of Pediatrics. Febrile seizures.
3. American Academy of Pediatrics, Steering Committee on
Quality Improvement and Management. Classifying
recommendations for clinical practice guidelines.
4. American Academy of Pediatrics. Committee on Quality
improvement, Subcommittee on Febrile Seizures. The
long-term management of a child with simple febrile
seizures. Pediatrics. 1999; 103:1307-9.
5. Lynnet GS, Ingrid ES. Febrile seizures. BMJ.
6. Waruiru C, Appleton R. Febrile seizures: an update.Arch
Dis Child. 2004;89:751-6.
7. World Health Organization. Iron Deficiency Anemia.
Assessment, Prevention and Control. A Guide for Program
Managers. WHO/NHD/013;Geneva: 2001.
8. Beard JL. Iron deficiency alters brain development and
functioning. J Nutr. 2003; 133:1468-72.
9. Jyoti B, Seth PK. Effect of iron deficiency on developing
rat brain. Indian J Clin Biochem. 2002;17:108-14.
10. Wike WM, Kiser WR. Iron deficiency anemia and febrile
convulsions. BMJ. 1996;313: 1205.
11. Ansun N, Shasi S. Susceptibility to febrile Seizures: More
than just a faulty thermostat. Canadian J Neurol Sci.
12. Pisacane A, Roland P, Sansone R, Impagliazzo N, Coppola
A, D’ Appuzo A. Iron Deficiency anaemia and febrile
convulsions: A case control study. BMJ. 1996;313:343.
13. Dawn SH, Jonatan T, Jerome Y, Don S. The association
between iron deficiency and febrile seizures in childhood.
Clin Pediatr. 2009;48:420-6.
14. Daud AS, Batieha A, Ekteish A, Gharaibeh N, Ajlouni S,
Hijazi S. Iron status: a possible risk factor for first febrile
seizures. Epilepsia. 2002;43:740-3.
15. Rajwanti KV, Praveen GD, Swati K, Ghosh K. Iron
deficiency as a risk factor for first febrile seizure. Indian
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 group.
WHAT THIS STUDY ADDS?
•Iron deficiency is a significant risk factor for simple febrile seizures in children 6 mo - 3 y age.