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ORIGINAL ARTICLE |
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Year : 2021 | Volume
: 34
| Issue : 2 | Page : 611-616 |
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Serum zinc and iron levels in children with febrile seizures
Ahmad T Mahmoud1, Maha A Albassuoni2, Sameh A Abd El Nabi1, Mona A. Youssef El-Behairy3
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 Submission | 02-Sep-2019 |
Date of Decision | 05-Oct-2019 |
Date of Acceptance | 07-Oct-2019 |
Date of Web Publication | 30-Jun-2021 |
Correspondence Address: Mona A. Youssef El-Behairy Shamma, Ashmoun, Menoufia Egypt
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/mmj.mmj_280_19
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 | | |
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 | | |
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 | | |
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 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 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 | | |
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 | | |
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 | | |
1. | Margaretha L, Masloman N. Correlation between serum zinc level and simple febrile seizure in children. Paediatr Indonesia 2010; 50:326–330. |
2. | Shinnar S, Glauser TA. Febrile seizures. J Child Neuro 2002; 17:1744–1752. |
3. | Waruiru C, Appleton R. Febrile seizures: an update. Arch Dis Child 2004; 89:751–756. |
4. | Jones T, Jacobsen SJ. Childhood febrile seizures: overview and implications. Int J Med Sci 2007; 4:110–114. |
5. | Mahyar A. The preventive role of zinc from communicable and non-communicable diseases in children. NCD Malaysia 2005; 4:21–25. |
6. | Johnston MV. Iron deficiency, febrile seizures and brain development. Indian Pediatr 2012; 49:13–15. |
7. | Bidabadi E, Mashouf M. Association between iron deficiency anemia and first febrile convulsion: a case–control study. Seizure 2009; 18:347–351. |
8. | Gencer H, Kafadar İ, Köse G, Yıldırmak Y. Relationship of febrile convulsion with iron deficiency anemia and zinc deficiency. J Acad Res Med 2016; 6:94–97. |
9. | Singh P, Mehta V. Is iron deficiency anaemia a risk factor for febrile seizures: a case control study. Int J Contemp Ped 2016; 3:1307–1311. |
10. | Fallah R, Tirandazi B, Ferdosian F, Fadavi N. Iron deficiency and iron deficiency anemia in children with first attack of seizure and on healthy control group: a comparative study. Iran J Child Neurol 2014; 8:18–21. |
11. | Afsharkhas L, Tavasoi A. Renal function in children with febrile convulsions. Iran J Child Neurol 2014; 8:57–61. |
12. | Sharawat IK, Singh J, Dawman L, Singh A. Evaluation of risk factors associated with first episode febrile seizure. J Clin Diag Res 2016; 10:10–13. |
13. | Mikati MA, Hani AJ. Seizures in childhood. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, (eds). Nelson textbook of pediatrics. 20 th ed. Philadelphia, PA: Elsevier; 2016. 4303–4307. |
14. | Kafadar İ, Akıncı AB, Pekun F. The role of serum zinc level in febrile convulsion etiology. J Pediatr Inf 2012; 6:90–93. |
15. | Ehsani F, Vahid-Harandi M, Kany K. Determination of serum zinc in children affected by febrile convulsion and comparison with control group. J Iran Med Sci Univ 2006; 12:219–276. |
16. | Izumi Y, Ishii K, Akiba K. Hypozincemia during fever may trigger febrile convulsion. Med Hypoth 1990; 32:77–80. |
17. | Pannerselvam K, Raju P, Mani S, Reddy SM, Sekar P. Serum zinc levels in children with simple febrile seizures. Int J Contemp Ped 2017; 2:424–427. |
18. | Kumar L, Chaurasiya OS, Gupta AH. Prospective study of level of serum zinc in patients of febrile seizures, idiopathic epilepsy and CNS infections. People's J Sci Res 2011; 4:1–4. |
19. | Ganesh R, Janakiraman L. Serum zinc levels in children with simple febrile seizure. Clin Pediatr 2008; 47:164–166. |
20. | Çelik K, Güzel E, Nalbantoğlu B, Güzel S, Özkul A, Elevli M, et al. Serum zinc levels in convulsions: Deficiency is indeed a risk factor manager?. Turk Klinikleri J Pediatr 2012; 21:1–6. |
21. | Kafadar İ, Akinci AB, Pekun F. The role of serum zinc level in febrile convulsion etiology. J Pediatr Infect 2012; 6:90–94. |
22. | Lozoff B, Beard J, Connor J. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006; 64:34–43. |
23. | Akbayram S, Cemek M, Büyükben A. Major and minor bio-element status in children with febrile seizure. Bratisl Lek Listy 2012; 113:421–423. |
24. | Modaresi M, Mahmoudian T, Yaghini O. Is iron insufficiency associated with febrile seizure? Experience in an Iranian hospital. J Comprehensive Pediatr 2012; 3:21–24. |
25. | Fallah R, Tirandazi B, Ferdosian F. Iron deficiency and iron deficiency anemia in children with first attack of seizure and on healthy control group: a comparative study. Iran J Child Neurol 2014; 8:18–23. |
26. | De Benoist B, Darnton-Hill I, Davidsson L, Fontaine O, Hotz C. Conclusions of the joint WHO/UNICEF/IAEA/IZiNCG interagency meeting on zinc status indicators. Food Nutr Bull 2007; 3:480–484. |
[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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