Invest Clin 62(2): 112 - 118, 2021 https://doi.org/10.22209/IC.v62n2a02

Corresponding author: Ayşe Tuğba Kartal. Ankara University Faculty of Medicine, Department of Pediatric Neuro-

logy, Ankara, Turkey. Phone: +90 0531 791 7064. E-mail: atugbakartal@gmail.com

Relationship between serum iron level

and febrile convulsion in children.

Ayşe Tuğba Kartal

and Zeynep Çağla Mutlu

Ankara University Faculty of Medicine, Division of Pediatric Neurology, Ankara, Turkey.

Kütahya Parkhayat Hospital, Department of Pediatrics, Kütahya, Turkey.

Key words: febrile convulsion; ferritin; fever; hemoglobin; iron.

Abstract. The aim of the present study was to evaluate the relationship

between febrile convulsion, serum iron levels and whole blood parameters. This

cross-sectional case-control study included patients aged 6 months-6 years-old

brought to the department of pediatrics of Kütahya ParkHayat Hospital with

febrile convulsions between January 2015 and December 2019. The patients

were divided into two groups as: febrile with convulsions (study group; n= 47)

and febrile without convulsions (control group; n= 35). Both groups were age

and sex-matched. Some blood parameters such as mean serum iron, ferritin,

Hb and MCV levels were used to compare the groups. Mean serum iron levels

of the study and control groups were 33.7 ± 2.1 μg/dL and 56.3 ± 7.4 μg/dL

(p<0.05), and serum ferritin levels were 27.3 ± 6.2 ng/mL and 31.1 ± 2.1 ng/

mL (p>0.05), respectively. Mean hemoglobin levels of the study and control

groups were 10.6 ± 1.7 g/dL and 11.1 ± 1.4 g/dL (p <0.05), and mean MCV

levels were 71.1 ± 1.2 fL and 73.2 ± 1.1 fL (p>0.05), respectively. In the light

of the findings of this study, the low serum iron and ferritin levels may be rein-

forcing factors for developing febrile convulsion. However, multicentre studies

with more patients are needed to reach a precise conclusion.

Iron level and febrile convulsion in children 113

Vol. 62(2): 112 - 118, 2021

Relación entre el nivel de hierro sérico y convulsiones febriles

en niños.

Invest Clin 2021; 62 (2): 112-118

Palabras clave: convulsión febril; ferritina; fiebre; hemoglobina; hierro.

Resumen. El objetivo del presente estudio fue evaluar la relación entre la

convulsión febril, el nivel de hierro en suero y los parámetros de sangre total.

Este estudio transversal de casos y controles incluyó pacientes de 6 meses a

6 años llevados a consulta al departamento de pediatría del Hospital Kütahya

ParkHayat con convulsiones febriles entre enero de 2015 y diciembre de 2019.

Los pacientes se dividieron en dos grupos: pacientes con convulsiones febriles

(grupo estudio; n= 47) y pacientes febriles sin convulsiones (grupo control; n=

35). Ambos grupos se emparejaron por edad y sexo. Para comparar los grupos

se utilizaron algunos parámetros sanguíneos, como los niveles medios de hierro

sérico, ferritina, Hb y MCV. Los niveles medios de hierro en suero de los grupos

de estudio y control se encontraron como 33,7 ± 2,1 μg / dL; 56,3 ± 7,4 μg /

dL (p <0,05), respectivamente. Los niveles de ferritina en suero fueron 27,3

± 6,2 ng / mL; 31,1 ± 2,1 ng / mL (p> 0,05), respectivamente. Los niveles

medios de hemoglobina del estudio y del grupo control fueron 10,6 ± 1.7 g/

dL; 11,1 ± 1,4 g/dLl (p <0,05), respectivamente, y los niveles medios de MCV

fueron 71,1 ± 1,2 fL; 73,2 ± 1,1 fL (p> 0,05), respectivamente. A la luz de

los resultados de este estudio, los bajos niveles de hierro y ferritina en suero

pueden ser factores de refuerzo para desarrollar convulsiones febriles. Sin em-

bargo, se necesitan estudios multicéntricos con más pacientes para tomar una

decisión precisa.

Received: 26-07-2020 Accepted: 17-01-2021

INTRODUCTION

The most common type of seizure in

children is febrile convulsion, which is gen-

erally characterized by a temperature of 38

°C or higher that occurs in children aged

6 months to 6 years and who do not have

evidence of intracranial infection, head trau-

ma, electrolyte imbalance, hypoglycemia

and drug use. Febrile convulsion peaks at

around 18 months, and its annual incidence

is 2%–5% (1). Febrile convulsion is classi-

fied into simple and complex types. Simple

febrile convulsion lasts for <15 min within

a 24-hour period, whereas the complex type

lasts for >15 min and occurs more than

once within a 24-hour period (2-4).

Iron deficiency is the most common nu-

tritional disorder worldwide, and it is most

frequently observed in children aged 6–24

months and in adolescents (5). Clinical find-

ings depend on the severity of anemia, age,

and presence of comorbidities. Iron is in-

volved in the synthesis of many proteins and

enzymes, and it also participates in the elec-

tron transport system (6). Unexplained fa-

tigue and pallor of the conjunctivae and skin

are the most common symptoms of iron de-

114 TuğbaKartalandÇağlaMutlu

Investigación Clínica 62(2): 2021

ficiency anemia (7). In some cases, diagnosis

is based only on serum iron and hemoglo-

bin (Hb) levels (8). In severe cases, cardiac

systolic murmur, hemodynamic instability,

breath-holding attacks, dyspnea at rest, and

syncope can be observed (8). In prolonged

cases, changes in epithelial cells, such as

atrophic glossitis, cheilitis, dry mouth and

hair loss, can be seen (9). Additionally, some

neurological problems (e.g., impaired psy-

chomotor and mental development) and

attention-deficit/hyperactivity disorder may

be found (10).

In recent studies, the relationship be-

tween iron deficiency and febrile convul-

sion draws attention (11, 12). It has been

shown that iron affects energy metabolism,

the neurotransmitter system and myelin

development in the brain. These effects of

iron deficiency may negatively affect brain

development (13). Additionally, according

to some authors, excessive amounts of pro-

inflammatory cytokines are released during

fever, and this phenomenon may aggravate

the negative effects of iron deficiency toward

the brain (6,13,14). However, there are not

enough studies to support this relationship

yet.

The aim of the present study was to

evaluate the relationship between febrile

convulsion and serum iron level, and some

blood parameters.

MATERIALS AND METHODS

This cross-sectional case–control study

included patients aged 6 months to 6 years

that were taken to the department of pedi-

atrics of ParkHayat Hospital with febrile con-

vulsions between January 2015 and Decem-

ber 2019. The electronic medical recording

system and patients’ files were used to get

information about the patients, and the cas-

es were selected according to the inclusion

and exclusion criteria

. The patients were di-

vided into two groups as: with febrile convul-

sion (study group; n= 47) and fever without

convulsion (control group; n= 35).

Febrile convulsion was diagnosed ac-

cording to the American Academy of Pedi-

atrics guidelines. Febrile convulsions are

defined as a type of seizure that occurs in

children between 6 months - 6 years olds, as-

sociated with fever (greater than 38°C), but

without acute intracranial infection, meta-

bolic disturbance or long-term neurological

conditions (15).

Inclusion and exclusion criteria for the

febrile convulsion group: patients aged 6

months to 6 years, and patients with a first

simple convulsion episode were included to

the study. Children under 6 months and over

6 years of age, patients with two or more

complex febrile convulsions, pchildren that

received iron treatment in the last three

months, with chronic inflammatory disease,

neurodevelopmental retardation, hemato-

logical disease, intestinal malabsorption syn-

drome and with missing data, were excluded

from the study.

Inclusion and exclusion criteria for con-

trol group: patients with the same age and

gender who were brought to the department

of pediatrics due to any febrile illness (with-

out any seizure) were included to the study.

The patients with central nervous system in-

fection or who had any seizure were exclud-

ed from the study.

Whole blood parameters (hemoglobin

(Hb), mean corpuscular volume (MCV), red

cell distribution width (RDW)) were mea-

sured with an automatic blood count device

LH 750 (Beckman Coulter, Miami, USA).

Iron and ferritin were determined with a Co-

bas C501 (ROCHE Berlin, Germany) analyz-

er. Anemia was defined by Hb levels of <10.5

g/dL in patients aged 6 months to 2 years

and by Hb levels of <11.5 g/dL in patients

aged 2–5 years (16). The normal ferritin lev-

el was set at >12 ng/mL, and the normal se-

rum iron level was considered to be >40 μg/

dL for children aged <1 year and >50 μg/dL

for those aged >1 year (17).

The study protocol was approved by the

local ethics committee and conducted ac-

cording to the Helsinki declaration. Given

Iron level and febrile convulsion in children 115

Vol. 62(2): 112 - 118, 2021

by Ethics Committee of Kütahya University

of Health Sciences (2020/07-03).

Statistic analysis

Data analysis was performed by using

the IBM SPSS 21.0 package program. Con-

tinuous variables were expressed as means ±

standard deviations and the qualitative vari-

ables in absolute frequiencies and percent-

ages. The independent samples t-Test and

chi-square tests were used to compare the

groups. A p-value less than 0.05 was consid-

ered statistically significant.

RESULTS

The demographic and laboratory char-

acteristics of the participants in the study

are presented in Table I. There were no dif-

ferences (p ≤0.05) in the mean age and the

male/female ratio of the study and control

groups. Mean serum iron level of the study

and control groups was found as 33.7 ± 2.1

μg/dL and 56.3 ± 7.4 μg/dL (p<0.05), re-

spectively, and serum ferritin level was found

as 27.3 ± 6.2 ng/mL and 31.1 ± 2.1 ng/

mL (p >0.05), respectively. Mean hemoglo-

bin level of the study and control groups was

found as 10.6 ± 1.7 g/dL and 11.1 ± 1.4

g/dL (p<0.05), respectively, and mean MCV

level was found as 71.1 ± 1.2 fL and 73.2 ±

1.1 fL (p >0.05), respectively.

Fever etiologies of febrile convulsion and

control groups were compared in Table II.

DISCUSSION

Iron has many biological effects, and

it is involved in important neurological pro-

cesses, such as neurotransmitter metabo-

lism, myelin formation, and brain energy

metabolism (18). According to some experi-

mental studies, in the case of iron deficien-

cy, along with that of gamma-aminobutyric

acid, iron concentration decreases in some

brain regions (hypothalamus, mesencepha-

lon, thalamus, hippocampus, and corpus

striatum) (19,20).

In the present study, serum ferritin and

iron levels were lower in the febrile convul-

sion group than in the control group; al-

though a significant difference was observed

only for iron. Similar results were found by

Hameed et al. and Fallah et al. Their results

TABLE I

THE DEMOGRAPHIC AND LABORATORY CHARACTERISTICS OF THE STUDY PARTICIPANTS.

Variable Febrile Convulsion Group (47)

Ẋ±SD

Control Group (35)

Ẋ±SD

Age (months) 24.3±1.1 25.4± 2.1 0.411

Gender % (n)

Female

Male

59.6 (28)

40.4 (19)

57.1 (20)

42.9 (15)

0.337

Hb (g/dL) 10.4±1.7 11.1±1.4 0.031

MCV (fL) 71.1±1.2 73.2± 1.1 0.401

RDW (%) 15.4±1.3 14.8±1.1 0.356

Ferritin (ng/mL) 27.3±6.2 31.1±2.1 0.053

Iron (μg/dL) 33.7±2.1 56.3±7.4 0.002

( ): Number of cases.

Ẋ±SD: mean ± standard deviation.

Hb: hemoglobin; MCV: mean corpuscular volume; RDW: red cell distribution width.

116 TuğbaKartalandÇağlaMutlu

Investigación Clínica 62(2): 2021

showed that serum ferritin and iron levels

were significantly lower in the febrile con-

vulsion group than in the control group (15,

21). By contrast, Kobrinsky et al. found that

serum ferritin level was lower in the control

group consisting of febrile patients without

convulsion, and they suggested that iron

deficiency is a protective factor for febrile

convulsion in acute febrile infection (22).

We speculate that the number of partici-

pants, the case selection, and the regional

nutritional habits of patients (the patients

included in our study has a diet unique to

the Mediterranean cuisine) may have caused

the differences in the results obtained in the

above studies.

In terms of Hb and MCV values, con-

flicting results were reported by different au-

thors who compared patients who had febrile

convulsion with those who had fever without

convulsion (1, 23). In a Turkey-based study,

Nalbantoglu et al. compared 94 patients with

febrile convulsion and 70 individuals with fe-

ver without convulsion, and they found that

the groups significantly differed in terms of

Hb levels. Mean corpuscular volume value

was lower in the febrile convulsion group,

but this difference was not significant (24).

In another study carried out by Aziz et al.

from Pakistan, Hb and MCV values were sig-

nificantly lower in patients with febrile con-

vulsion (25). Compared with these studies,

the India-based study conducted by Mehta et

al. did not find any significant difference be-

tween the groups, although the Hb and MCV

values were lower in febrile convulsion group

(26). In our study, Hb value was significantly

lower in the patients with febrile convulsion,

a finding that is similar to that of the first

two studies. Mean corpuscular volume value

was also found to be lower in the febrile con-

vulsion group, but this difference was not

significant. The differences in the results of

the abovementioned studies were possibly

due to the number of patients included.

According to the literature, febrile con-

vulsion usually develops due to an upper re-

spiratory infection (27, 28). Consistent with

this information, upper respiratory tract

infections were the most common etiolog-

ic factor causing febrile convulsion in the

study of Chung et al. (33%) and Delpisheh et

al. (42,3%) (29, 30). Our results are also in

agreement with the findings of these studies.

Our study has limitations, including its

retrospective nature, its relatively few and

heterogeneous participants, its inclusion of

ferritin, which is an acute phase reactant,

and its failure to account for the patients’

nutritional habits.

On the basis of the present findings,

low serum iron and ferritin levels may be

considered as reinforcing factors for the de-

velopment of febrile convulsion. Therefore,

TABLE II

COMPARISON OF FEVER ETIOLOGY OF GROUPS.

Fever etiology Febrile Convulsion Group (47)

% (n)

Control Group (35)

% (n)

Upper respiratory tract infection 44,6 (21) 42,8 (15) 0.413

Acute otitis media 19,1 (9) 20 (7) 0.447

Lower respiratory tract infection 8,5 (4) 11,4 (4) 0.323

Gastroenteritis 17 (8) 17,1 (6) 0.319

Urinary tract infection 4,2 (2) 2,8 (1) 0.367

Influenza 6,3 (3) 5,7 (2) 0.403

(n ): Number of cases.

Iron level and febrile convulsion in children 117

Vol. 62(2): 112 - 118, 2021

the evaluation of the iron status should be

encouraged in children with febrile convul-

sion, and iron supplementation is possibly

beneficial in the treatment and prevention

of febrile convulsion in children.

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