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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 2  |  Page : 611-616

Serum zinc and iron levels in children with febrile seizures


1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Pediatrics, Ashmoun General Hospital, Menoufia, Egypt

Date of Submission02-Sep-2019
Date of Decision05-Oct-2019
Date of Acceptance07-Oct-2019
Date of Web Publication30-Jun-2021

Correspondence Address:
Mona A. Youssef El-Behairy
Shamma, Ashmoun, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_280_19

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  Abstract 


Objective
To assess serum zinc and iron levels in children with febrile seizures (FS) and their relation to clinical findings.
Background
Zinc and iron deficiencies are assumed to be common in children with FS.
Patients and methods
This case–control study was conducted on 80 Egyptian children (from 6 months to 5 years old) attending the emergency room and pediatric departments. The children were divided into group I which included 20 patients with FS and group II which included 20 patients with afebrile seizures; group III included 20 febrile patients without seizures or history of previous seizures; and group IV included 20 clinically healthy children, age and sex matched. Detailed history, thorough physical examination, routine investigations, and serum iron and zinc levels were done.
Results
There were statistically significant differences between group I (children with FS, n = 20), group II (children with afebrile seizures, n = 20), group III (children with febrile illness, n = 20), group IV (healthy children, n = 20) regarding zinc and iron levels. The mean serum zinc levels were significantly low in group I than the other three groups (68.25 ± 11.2, 96.1 ± 6.05, 99.3 ± 6.38, 97.2 ± 6.58, respectively) (P = 0.001). Also, the mean serum iron levels were significantly low in group I than the other three groups (0.43 ± 0.20, 0.88 ± 0.12, 0.86 ± 0.13, 0.83 ± 0.15, respectively) (P = 0.001).
Conclusion
Children with FS had significantly low serum zinc and iron levels in comparison with afebrile seizures, febrile patients, and healthy children.

Keywords: afebrile seizures, febrile illness, febrile seizures, serum iron, serum zinc


How to cite this article:
Mahmoud AT, Albassuoni MA, Abd El Nabi SA, El-Behairy MA. Serum zinc and iron levels in children with febrile seizures. Menoufia Med J 2021;34:611-6

How to cite this URL:
Mahmoud AT, Albassuoni MA, Abd El Nabi SA, El-Behairy MA. Serum zinc and iron levels in children with febrile seizures. Menoufia Med J [serial online] 2021 [cited 2024 Mar 28];34:611-6. Available from: http://www.mmj.eg.net/text.asp?2021/34/2/611/319683




  Introduction Top


The International League against Epilepsy defines febrile seizures (FS) as seizures occurring in childhood after 1 month of age, associated with a febrile illness that is not caused by an infection of the central nervous system or metabolic disturbance [1]. FS can be separated into two categories, simple and complex. A simple FS is isolated, brief, and generalized [2]. A complex FS is one with the focal onset one that occurs more than once during a febrile illness or one that lasts for more than 10–15 min [3]. The pathogenesis of FS is unknown in most of the cases, but various factors have been considered in the etiology as alteration in some elements and a genetic predisposition [4]. Zinc is an important micronutrient that plays a significant role in growth and development, immune system response, enzymatic activity of different organs, proteins and cellular metabolism, neurological functions, nerve impulse transmission, and hormone release [5]. Iron deficiency is one of the most frequent micronutrient deficiencies that affect at least one third of the population of the world. Anemia is the most common clinical manifestation of iron deficiency, but other organs and systems may also be affected. The effect of iron deficiency in the developing brain and mechanisms such as altered development of hippocampus neurons, impairment of energy metabolism, delayed maturation of myelin, slowed visual-evoked and auditory-evoked potentials and alterations in synaptic neurotransmitter systems including norepinephrine, dopamine, glutamate, gamma-amino butyric acid, and serotonin may be responsible for these symptoms [6]. Iron and zinc are nutritional elements needed not only for the synthesis of hemoglobin (Hb), but also essential for enzymes involved in neurochemical reactions, thus, iron and zinc deficiencies may predispose to other neurological disturbances like FS [7]. The aim of this study was to assess serum levels of zinc and iron in children with FS and their relations to clinical findings.


  Patients and methods Top


This case–control study was conducted on 80 children of 6 months to 6 years old, 47 men and 33 women to measure serum iron and zinc in children with FS, those with seizures without fever, those febrile without epileptic attacks in comparison to healthy children. The patients were collected from the pediatric departments of Menoufia University in the period from February 2017 till February 2018.

Ethical consideration

Approval of the study protocol by Ethical Scientific Committee of Faculty of Medicine, Menoufia University was obtained and written consents were taken from the parents of children before their enrollment in the study.

Inclusion criteria

Children (6 months–5 years) with seizures whether simple or complex, febrile or afebrile.

Exclusion criteria

Children with known zinc and iron supplementation.

Method of sampling

A measure of 3 cm3 sample of venous blood was collected by sterile syringes; 1 ml was put on EDTA for performing complete blood count by using a Coulter cell counter; the rest of the blood was kept in plain tubes, left to clot and serum was separated by centrifugation; the resultant serum was stored at −20°C till the time of serum zinc and iron assay.

All patients were subjected to the following: detailed history taking with special emphasizes on the duration of fever, type of convulsions, duration of FS, what relieves the seizures, frequency of attacks, number of fits, and immunization history. Clinical examination: general examination and systemic examination specially neurological laboratory investigations: complete blood count using a coulter cell counter, quantitative C-reactive protein. Quantitative determination was done by using a full automated chemistry analyzer; random blood sugar and serum electrolytes (sodium, potassium, and calcium) were measured by an AU480 system from Beckman Coulter (Brea, California, USA. Beckman Coulter, Inc. USA) using a biochromatic (405–510 nm) rate technique to exclude other causes of seizures (hypoglycemia, hypocalcemia, hypokalemia, hyponatremia, or hypernatremia). Serum iron and serum zinc was assessed by colorimetric measures. Other investigations such as lumbar puncture, electroencephalogram, and neuroimaging were done when indicated.

Statistical analysis

Data were collected, tabulated, and statistically analyzed using an IBM Personal Computer with the Statistical Package for Social Sciences, version 22 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were presented in the form of mean, SD, range; and qualitative data were presented in the form of numbers and percentage. χ2 test was used to study the association between two qualitative variables. Student's t test was used for comparison between two groups having quantitative variables. Kruskal–Wallis test (nonparametric test) was used for comparison between three or more groups not normally distributed having quantitative variables. Analysis of variance test is used to check if the means of two or more groups are significantly different from each other. Post-hoc test was used to determine if the relationships between groups were significant. P value less than 0.05 was considered statistically significant.


  Results Top


There were no significant statistical differences between the four groups regarding age and sex of children [Table 1]. Also, there were no significant statistical differences between the four studied groups of children regarding their serum Na, K, Ca, and glucose levels [Table 2]. This study has shown that there is significant differences between four groups in Hb level; it is low in children with FS in comparison to children with group II with a P value of 0.001, group III with a P value of 0.016; and group IV with a P value of 0.03; and also the mean total leukocyte count of children with FS was significantly higher than group IV and those with group II, P value 0.001, but not significantly higher in comparison to group III, while C-reactive protein was significantly higher in groups I and III with a P value of 0.001 in comparison with group IV [Table 3].
Table 1: Age and sex among the four studied groups

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Table 2: Serum electrolytes and random glucose among the studied groups

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Table 3 Complete blood count and C-reactive protein findings among the four studied groups

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Serum zinc levels in children with FS (group I) were significantly low in comparison with groups II, III, and IV (P = 0.001). There were no significant differences in serum zinc level between children with group II and both groups III and IV. Also, serum iron levels in children with FS (group I) were significantly low in comparison with groups II, III, and IV (P = 0.001) and there were no significant statistical differences of serum iron levels between children with afebrile seizures (group II), febrile children (group III), and healthy control (group IV) [Table 4]. Serum zinc on a cutoff more than 79.0 ng/ml has a sensitivity of 80% and specificity of 100% for prediction of FS with positive predictive value (PPV) = 100% and negative predictive value (NPV) = 83%, so we can consider serum zinc as a good negative test for FS. Also, serum iron on a cut off more than 0.551 ng/ml has a sensitivity of 75% and specificity of 95% for prediction of FS with PPV = 94% and NPV = 79%, so we can consider serum iron as a good negative test for FS [Table 5] and [Figure 1].
Table 4: Serum zinc and iron level in the four studied groups

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Table 5: Agreement (sensitivity, specificity, and accuracy) to predict febrile seizures patients (vs. febrile group III and control group IV) of zinc and iron

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Figure 1: ROC curve for serum zinc to predict febrile seizure patients (vs. febrile group III and control group IV).ROC, receiver operating characteristic.

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  Discussion Top


In this study, the mean ages of the studied groups were 1.83 ± 0.97, 2.54 ± 1.21, 2.30 ± 1.25, and 2.19 ± 1.13 years in groups I, II, III, and IV, respectively, with no statically significant differences between the four groups regarding age with a P value of 0.287 and sex of children with a P value of 0.452. This agrees with Gencer et al. [8], the mean age of their patients with FS was 25.8 ± 11.9 months. Also, with Singh and Mehta [9], the mean age of their FS group was 27.33 ± 14 months. There was no statistical difference in distribution as per age, sex, socioeconomic strata, and malnutrition in both groups. Also Fallah et al. [10] found no statistically significant differences as regards sex distribution, mean age, and weight. In this study, there were no significant statistical differences between the four groups regarding serum electrolytes and glucose, which agrees with Afsharkhas and Tavasoi [11]. In contrast to our study, Sharawat et al. [12] found that serum sodium, serum calcium, and random blood sugar values of FS patients were significantly lower than controls, while Mikati and Hani [13] considered that a low sodium level at the time of seizures attack is associated with higher risk of recurrence of FS within the following 24 h. Regarding laboratory findings in our study, we found significant differences between four groups in Hb level; it is low in children with FS in comparison to children with afebrile seizures (group II) with a P value of 0.001, fever group (group III) with a P value of 0.016, and healthy (group IV) with a P value of 0.03. This agrees with Sharawat et al. [12] who found that Hb level among children with FS was significantly lower than control groups as they found that more than 60% of children with FS had iron-deficiency anemia and they observed that low serum iron level was a risk factor for first FS. In the present study, serum zinc levels in children with FS (group I) were significantly low in comparison with groups II, III, and IV. There were no significant statistical differences in serum zinc level between children with afebrile seizures (group II) and both febrile children (group III) and healthy control (group IV). The reason for reduction of serum zinc level in patients affected with FS is not clear. However, fever and acute infection may have some roles in developing such condition [14]. It is believed that the release of tumor necrosis factor and interleukin II during fever or tissue injury may result in reduction of serum zinc level [15]. Izumi et al. [16] proposed that the hypozincemia during fever trigger the NMDA receptor, one of the members of glutamate family of receptors, which may play an important role in the initiation of epileptic discharge during FS. Our results are in agreement with Pannerselvam et al. [17] who found that serum zinc levels were low in the FS group than the control. Also, Kumar et al. [18] and Ganesh and Janakiraman [19] found that mean serum zinc levels were significantly lower in children with FS as compared with controls. In contrast to our study, Çelik et al. [20] and Kafadar et al. [21] found that there were no significant statistical differences between group I and control groups.

In our study, serum iron levels in children with FS (group I) were significantly low in comparison with other groups. There were no significant statistical differences of serum iron levels between groups II, III, and IV. The present study agrees with the study of Lozoff B et al. [22] and Akbayram et al. [23] as they found statistically significant differences between FS patients and control groups as serum iron was less in the patient group than in the control group, while Modaresi M et al. [24] found that serum iron levels in children with both febrile and afebrile seizures were lower than in the control group. Iron deficiency may play an important role in inducing seizures from the following mechanisms: decrease of gamma-amino butyric acid inhibitory neurotransmitter due to change in its metabolism; change in neuron metabolism; reduction of enzymes such as monoamine and aldehyde oxidases; and impairment in oxygenation and energy metabolism of the brain [25].

In this study, serum zinc on a cutoff more than 79.0 ng/ml has a sensitivity of 80% and specificity of 100% for prediction of FS with PPV = 100% and NPV = 83%, so we can consider serum zinc as a good negative test for FS. In the study of De Benoist et al. [26], serum zinc level of less than 65 μg/dl was taken as a cutoff for zinc deficiency. Also, serum iron on a cutoff more than 0.551 ng/ml has a sensitivity of 75% and specificity of 95% for prediction of FS with PPV = 94% and NPV = 79%, so we can consider serum iron as a good negative test for FS. Association between FS and iron deficiency is explored all over the world, the results are conflicting.


  Conclusion Top


Children with low serum zinc and iron levels are more prone to get FS than children with normal serum zinc and iron levels. Both low levels of serum zinc and iron are considered as risk factors for FS; their correction may lessen the risk.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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