Iron deficiency anemia as a risk factor for simple febrile seizures
V O L .
Iron deficiency anemia as a risk factor for simple febrile seizures
Children Hospital Lahore 0
Children Hospital Lahore 0
Abdul Islam Hanif Hanif 0
0 Department of Pediatric Neurology Children Hospital lahore
Iron deficiency anemia as a risk factor for simple febrile seizures
1Department of Pediatric Neurology, 2Department of Pediatrics Medicine
Date of submission: January 11, 2017 Date of revision: May 21, 2017 Date of acceptance: June 1
OBJECTIVE: To determine the association of iron deficiency anemia with simple febrile seizures in children
presenting in a tertiary care hospital.
DESIGN: Case controls study.
Place & duration of study: Department of Pediatric Neurology, The Children's Hospital and Institute of Child health,
Lahore, Pakistan from June 1, 2012 to May
SUBJECTS & METHODS: A total 400 (200 cases & 200 controls) were included in the study. Children with febrile
seizures and controls were included without seizures. Informed consent was taken from parents of each child.
Children were divided into two groups, cases and controls, on the basis of presence or absence of seizures. Serum
ferritin level, Hb, HCT and MCV levels were assessed.
RESULTS: Mean Hb level in cases and controls were 9.86±2.28 and 9.48±1.86 mg/dl respectively. Mean RDW
among cases and controls was 28.82±10.78 and 31.10±15.97. Mean MCV value in cases and controls was
69.03±10.84 and 72.91±11.63 respectively. Mean HCT level in cases was 29.75±5.22 and in controls mean HCT
level was 32.85±11.86. Among cases 93(46.5%) children and among controls 56(28%) children had iron deficiency
anemia. Odds ratio of 2.235 shows that cases i.e. children who had iron deficiency anemia had 2.235 more
chances of seizures as compared to children without anemia.
CONCLUSION: Iron deficiency anemia is considered as a risk factor for febrile seizures in children. (Cases vs
controls 46.5% vs. 28%)
KEY WORDS: Iron deficiency anemia, Simple febrile seizures, Hemoglobin,
Febrile seizures (FS) are the commonest cause of
seizures in children, occurring in 2-5% of children with
lots of burden on health care system and cause of
anxiety for parents.1 Febrile Seizures episodes also
cause a great deal of agony and psychological
trauma to parents. About 2-7% of children who
develop FS proceed to develop epilepsy later in life.2
Iron deficiency is the commonest micro nutrient
deficiency worldwide, and is a preventable and
treatable condition.3 Iron deficiency is ranked at the
top of three global “hidden hungers” (Iron, Iodine,
Vitamin A: sub-clinical deficiency without visible signs
of deficiency) with about one fifth of world's
population children in the developing world, iron is the
most common single-nutrient deficiency.5
In Pakistan, prevalence of IDA is very high. According
to National Nutrition Survey of Pakistan 2011, 33.4%
children are suffering from IDA at national level.6 Iron
is needed for brain energy metabolism, for
metabolism of neurotransmitters and for my elination.
A lack of sufficient iron intake may significantly delay
the development of the central nervous system as a
result of alterations in morphology, neurochemistry,
Various studies showed that iron Deficient children
have more likelihood of developing FS.8-10 In one
study 31.85% children with FS had evidence of IDAas
compared to 19.6% without FS and a strong
association was obtained (p-value = 0.014). It was
concluded that children with FS are almost twice as
likely to have IDA as compared to children with a
febrile illness without seizures. IDA can be regarded
as a risk factor that predisposes to febrile seizures in
children.11 Instead of that. In some of the studies
these findings have not been confirmed.12
Kumari, et al. wrote that iron deficiency is also a risk
factor for febrile seizures in children 6 months to
P A K I S T A N J O U R N A L O F N E U R O L O G I C A L S C I E N C E S 3 6
three years of age showing a highly significant
association between iron deficiency and febrile
seizures. As expected, a family history of febrile
seizures or epilepsy in first degree relatives was also
linked to the occurrence of febrile seizures in these
children. The findings are consistent with another
recent case-control study from Kenya of children 3-156
months of age, which reported that iron deficiency is a
risk factor for simple febrile seizures but not for other
types of acute seizures.8,13
There is a debate going on whether there is an
association between iron deficiency and the risk for
febrile seizures or not. Several studies suggest a
positive correlation between iron deficiency and febrile
seizures; the iron dependent metabolism of several
neurotransmitters has been suggested as a possible
mechanism for this association. Conversely, other
studies have suggested a negative association or no
association between iron deficiency and febrile
According to one of local case control study, 31.85% of
cases had iron deficiency anemia whereas, 19.6% of
controls were found to have iron deficiency anemia.11
These results suggest that iron deficiency anemia was
less frequent among the cases with febrile convulsion,
as compared to the controls, and there is not a
protective effect of iron deficiency against febrile
Rationale of this study is to determine the association
of iron deficiency anemia with simple febrile seizures in
children presenting in a tertiary care hospital. Iron
deficiency anemia has high prevalence in Pakistan
and febrile seizures constitute a major burden of
PATIENTS AND METHODS
To determine the association of iron deficiency anemia
with simple febrile seizures in children presenting in a
tertiary care hospital
Following operational definitions will be used. Simple
febrile seizures are defined as brief (<15-minute)
generalized seizures that do not recur during a 24-hour
period in a febrile child (temp>100oC) who is otherwise
neurologically healthy and without evidence of any
neurologic abnormality before and after episode of
seizures and without any metabolic disturbance.
Iron deficiency anemia was labeled as if Hb<10gm/dl,
Hct<33%, RDW>17 and MCV<70fl in blood of febrile
child. It was a case control study conducted at
emergency and Neurology department of The
Children's Hospital and The Institute of Child Health
Lahore from January 1st, 2013 to September 20th 2013
with a sample size was of 400 children. There were 200
cases in each group is calculated with 80% power of
test, 5% level of confidence and taking expected
percentage of IDA i.e. 31.85% in cases and 19.6% in
controls in children with simple febrile seizures
presenting in a tertiary care hospital. We used
nonprobability, purposive sampling technique for sample
collection. Inclusion criteria was children aged 6
months to 5 years of either gender with febrile illness
CASES: Children with Seizures (as per operational
CONTROLS: Children without seizures
Exclusion criteria was children with atypical febrile
seizures (on clinical examination), afebrile seizures
(through history and medical record), children having
signs of CNS infection (clinical examination and
positive bacteria on CSF examination), children with
other chronic illnesses e.g. liver disease (AST>40IU,
ALT>40IU), kidney disease (creatinine>1.2gm/dl),
Cardiac problems (through medical record and
examination), h/o asthma, children already on iron
therapy (through medical record)
After approval from hospital ethical committee, 400
children fulfilling the selection criteria was included in
the study. Informed consent was taken from parents of
each child. Demographic details (name, age, sex,
weight and contact) were also being obtained.
Children were divided into two groups, cases and
controls, on the basis of presence or absence of
seizures. Then blood sample was drawn by a staff
nurse specially appointed for this job through a 5cc BD
syringe. Blood samples were sent to the laboratory of
the hospital for assessment of serum ferritin level, Hb,
Hct and MCV level in the blood. Reports were retrieved
and discussed with senior consultant pathologist. Iron
deficiency anemia was labeled (as per operational
definition). All this information was recorded on
predesigned proforma. Data was entered and analyzed
through computer based software i.e. SPSS version
17. Mean and standard deviation was calculated for
continues variables like age, weight, hemoglobin,
hematocrit, MCV and ferritin level. Frequency, Multiple
bar chart, Line chart and percentage was calculated for
qualitative variables like gender and IDA. Odds ratio
was calculated to see the association between iron
deficiency anemia and simple febrile seizures. OR>1
was considered statistically significant.
A total of 400 children were included in the study. 200
were cases and 200 were controls. Among cases
mean age was 2.08±1.07 years. While among controls
mean age was 3.21±1.69 years respectively. (Table-I)
cases shows that there were 130 male and 70 female
children while among controls there were 145 male
and 55 female children. Among cases 155 children
weight was <10 Kg and only 45 children weight was
>10 Kg. While in controls only 175 children weight was
<10Kg and 25 children's weight was >10Kg. Among
cases mean temperature was 101.28±1.16. Minimum
and maximum temperature in cases was 100 and 103.
Mean temperature among controls was 100.21±0.40.
Minimum and maximum temperature among controls
was 100 and 101 respectively. (Table-II) Mean Hb
level in cases and controls was 9.86±2.28 and
9.48±1.86 mg/dl. Minimum Hb among cases and
controls was 5.50 and maximum Hb was 13.50 and
13.30 respectively. (Table-III) Mean MCV value in
cases and controls was 69.03±10.84 and 72.91±11.63
respectively. Minimum value of MCV among cases and
controls was 15 and 86. Mean HCT level in cases was
29.75±5.22. Minimum and maximum level of HCT in
cases was 20 and 38 while in controls mean HCT level
was 32.85±11.86 with minimum and maximum value of
HCT as 28.50 and 80 respectively. Iron deficient
anemia was defined as per operational definition.
Among cases 93(46.5%) children and among controls
only 56(28%) children had iron deficiency anemia.
Among cases more children had iron deficiency
anemia as compared to that of controls. Odds ratio of
2.235 shows that cases i.e. children who had seizure
they had 2.235 more chances that will have iron
deficiency anemia s compared to that of those children
without seizure. All these results are statistically
significant with odd ratio of 2.235 (1.475-3.386).
Febrile convulsions are the ones that occur in the
presence of fever with no evidence of underlying CNS
infection based on history, clinical examination and
relevant laboratory tests. Febrile convulsions occur in
2-5% of all children with a recurrence rate of 30-40%.
Generally the children, 6 months to 5 years of age are
more prone to this disease. However, age for peak
incidence is 14 to 18 months which overlaps with that
of iron deficiency a.emia which is from 6 to 24
In developing countries 46-66% of children less than 4
years of age are anemic and 50% of them have iron
deficiency anemia. Its prevalence among the Pakistani
children is nearly 65%.19 It is established that iron is a
key player in various metabolic transactions, therefore,
must be provided at sufficient levels to sustain the
normal functioning of the body. Iron is also essential for
enzymes involved in neurochemical reactions.
However its deficiency can affect several organs and
cause malfunctioning of different systems of the body
including neurological symptoms like behavioral
changes, poor attention span and hearing deficits in
Febrile convulsion is one of the most common
childhood emergency presented in emergency rooms
with a frequency of about 2-5% in America and Europe
and 6-9% in Japan. It is slightly more common in males
and the predominant age for seizures in children is
found to be between 6 months to 5 years.21
Factors increasing the risk of recurrence are a family
history of febrile convulsions, first attack at the age less
than 12 months, and the intensity and duration of the
fever. Iron deficiency is one of the most prevalent
nutrition associated clinical problems in the world.
Emerging data from various studies reflects that 2.5-5
billion people including infants between 6 and 24
months of age are affected with this disorder. In a
number of studies a possible association of iron
deficiency and febrile seizures has been reported.22,23
In this study mean age of cases and controls was
2.08±1.07 and 3.21±1.69 years. While gender
distribution shows that among cases there were 130
male and 70 female children while among controls
there were 145 male and 55 females. Overall male
children were dominating females in this study. In
contrast, some studies show contradiction to our
findings and those cited elsewhere. Bidabadi et al
found that mean age of the cases was 22.86 (months)
while that of control was 21.91 months. On the similar
grounds, the studies of Susan et al show evidence of
divergent results as compared to our findings; the
mean age of cases was found to be 39 months and the
mean age of controls was 35 months.24
According to the results of a local case control study in
which association between iron deficiency anemia and
febrile seizures in children was determined. Results of
the study shows that 31.85% of cases (50 out of 157)
had iron deficiency anemia whereas, 19.6% of controls
(30 out of 153) were found to have iron deficiency
anemia as revealed by low levels of hemoglobin level,
serum ferritin level, mean corpuscular hemoglobin
concentration and mean corpuscular volume. Odds
ratio was 1.93.11,25 These results are consistent with the
results reported by Sherjil A. However Odds Ratio of
this study was higher as that of reported by Sherjil A as
well as percentage of iron deficiency anemia was also
Results of an Iranian case control study showed iron
deficiency anemia as 44% in cases and 48% in
controls. These results suggest that iron deficiency
anemia was less frequent among the cases with febrile
convulsion, as compared to the controls, and there is
not a protective effect of iron deficiency against febrile
convulsions.12 Results of this study are contradicting to
the results reported by Bidabadi E. An Indian case
control study showed iron deficiency anemia among
cases as 63.6% and 24.7% among controls with an
Odds ratio of 5.34(3.27-8.73). Keeping these findings
in mind the author concluded that Iron deficiency is a
significant risk factor for simple febrile seizures in
children of age group 6 months to 3 years.8,25
An Indian case control study showed iron deficiency
anemia among cases as 63.6% and 24.7% among
controls with an Odds ratio of 5.34(3.27-8.73). Keeping
these findings in mind the author concluded that Iron
deficiency is a significant risk factor for simple febrile
seizures in children of age group 6 months to 3
Results of local study from Rawalpindi and by Ghasem
Miri-Aliabad are similar to the results of this study.
While Derakhshanfar H reported resutls are
contradcited to the results of this study.11,27
A recent study from Rawalpindi Pakistan determined
the association of iron deficiency anemia with febrile
seizures. Among cases 64% had low serum ferritin
level while among controls 42% had low serum ferritin
Another Iranian study reported that iron deficiency
anemia in 44.6% cases in contrast to 58.4% controls
Ghasem Miri-Aliabad from Iran in his study reported
iron deficiency anemia as 44% and 36% among cases
and controls.30 Results of this study is consistent with
the results of Indian study but Odds ratio reported by
Indian study was high than that of this study. i.e. 5.34
and in this study.12,31
To conclude, it becomes important to evaluate iron
deficiency anemia among children who had febrile
seizures to prevent immediate complications, public
health burden and cost of medical care bear either by
parents and government. Among developing
countries, anemia is more prevalent among children
with febrile seizures. Moreover, iron plays an important
role in normal brain development and metabolism;
consequently its down regulation may halt many
substantive physiological functions and could lead to
initiation of febrile convulsions.
Iron deficiency anemia is considered as a risk factor
for children with febrile seizures. Results shows
twice the risk of iron deficiency anemia for children
with febrile seizures. Treatment with oral iron therapy
is cost effective and easy remedy to prevent further
episodes of febrile seizures.
AGE FOR CASES & CONTROLS
(age in years)
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