|Year : 2020 | Volume
| Issue : 3 | Page : 882-885
Association of iron deficiency anemia with simple febrile seizures: a hospital-based observational case–control study
Jehangir A Bhat1, Sajad A Sheikh2, Sami U Bhat3, Roshan Ara1
1 Department of Pediatrics, Vikas Hospital Pvt. Ltd, New Delhi, India
2 Department of Gastroenterology, Vikas Hospital Pvt Ltd, Najafgarh, New Delhi, India
3 School of Chemistry, Jiwaji University, Gwalior, Madhya Pradesh, India
|Date of Submission||09-Feb-2019|
|Date of Decision||23-Feb-2019|
|Date of Acceptance||05-Mar-2019|
|Date of Web Publication||30-Sep-2020|
Jehangir A Bhat
Department of Pediatrics Vikas Hospital Pvt Ltd, New Delhi
Source of Support: None, Conflict of Interest: None
To reveal the association of iron deficiency anemia with simple febrile seizures.
Iron deficiency anemia has aa defined role in a variety of neurological and psychological problems in children such as stroke, behavioral, and cognitive problems. Therefore, it is hypothesized that iron deficiency anemia may have a role in febrile seizures.
Patients and methods
It was a hospital-based observational case–control study conducted on 320 children of age group 6–59 months. Children were divided into groups. Cases (160) who presented with simple febrile seizures and controls (160) who had fever of short duration without any type of seizure or abnormal body movement. At the time of presentation to hospital, venous blood sample for routine investigations along with complete blood count of all children included in study were sent to laboratory. All data were tabulated and analyzed with relevant statistical tests.
Iron deficiency anemia is prevalent more (nearly > 5 times) in children who has simple febrile seizures than in normal children. Thus, evaluation for iron deficiency should be done in every child who present with simple febrile seizure.
Iron deficiency was recorded in 42 and 12.5% of cases and controls, respectively. Statistically significant association was seen between iron deficiency anemia and simple febrile seizures (P = 0.001) with odds ratio of 5.139. All hematological parameters which define iron deficiency anemia were low and statistically significant in cases as compared to controls.
Keywords: complete blood count, hematological parameters, iron deficiency anemia, odds ratio, simple febrile seizure
|How to cite this article:|
Bhat JA, Sheikh SA, Bhat SU, Ara R. Association of iron deficiency anemia with simple febrile seizures: a hospital-based observational case–control study. Menoufia Med J 2020;33:882-5
|How to cite this URL:|
Bhat JA, Sheikh SA, Bhat SU, Ara R. Association of iron deficiency anemia with simple febrile seizures: a hospital-based observational case–control study. Menoufia Med J [serial online] 2020 [cited 2020 Oct 20];33:882-5. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/882/296672
| Introduction|| |
Brain consists of nerve cells that usually communicate with each other through electrical activity, thus, controlling and regulating all voluntary and involuntary responses in the body. When region(s) of the brain receives a burst of abnormal electrical signals that temporarily interrupt the normal electrical brain function, a seizure occurs. Transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain is defined as a seizure. Febrile seizures are the seizures which are associated with fever of above 38°C (100.4 F) which occur above 6 and below 60 months of age, in the absence of any central nervous infections, metabolic disturbances, and any prior afebrile seizures . Febrile seizures are divided into simple/typical and complex/atypical febrile seizures. Simple febrile seizures are usually generalized tonic clonic type, lasting less than or equal to than 15 min and does not reoccur within 24 h in neurological and psychomotor normal children ,. Complex febrile seizures last more than 15 min, reoccurs within 24 h, and can be focal or generalized with postictal neurological deficit like Todd's palsy or with prior neurological deficit. Various factors have been described in the pathophysiology of febrile seizures such as:
- Infections like bacterial and viral 
- Temperature susceptibility of immature brain 
- Interleukins, circulating toxins association 
- Micronutrient deficiency and iron deficiency .
Role of micronutrients such as copper, zinc, magnesium, and selenium  have been described in association with febrile seizures. Micronutrients appear to play a vital role by their ability to modulate neurotransmission by acting on ion channels as well as coenzyme activity . Extensive research is going on to discover new risk factors which increase the incidence of febrile seizures like 25 hydroxy vitamin D, iron status, vitamin B6, etc.
The aim of our study was to find the association of iron deficiency with simple febrile seizures, so that by modifying the iron status of children, incidence of simple febrile seizures can be reduced.
| Patients and Methods|| |
It was a prospective observational case–control study conducted on 320 children of age group 7–59 months in the City Max Hospital and Research Centre, Tohana, Haryana for a period of 2 years from May 2013 to April 2015. One hundred and sixty children who presented with simple febrile convulsion were considered for this study and 160 children for concurrent controls were selected from the same setting of the same age group who present with short duration of fever (<3 days) but without seizures. Simple febrile seizures were defined as per the American Academy of Pediatrics definition  [febrile seizures are the seizures which are associated with fever of above 38°C (100.4 F) which occur above 6 and below 60 months of age, in the absence of any central nervous infections, metabolic disturbances, and any prior afebrile seizures].
Children of the above-mentioned age group who presented with simple febrile seizure were included in this study.
Children having cerebral palsy, seizure disorder, chronic diseases, dysmorphic and syndromic features, on anticonvulsants, chronic diarrhea, and metabolic disorders were excluded. Children who presented with electrolyte imbalance (sodium, calcium, etc.), hypoglycemia, meningitis, and encephalitis were also excluded.
Iron deficiency was defined as per the WHO criteria : hemoglobin less than 11 g/dl, mean corpuscular volume (MCV) less than 72 fl, mean corpuscular hemoglobin (MCH) less than 25 pg, mean corpuscular hemoglobin concentration (MCHC) less than 30 g/dl, total iron-binding capacity more than 210 μg/dl, transferrin saturation less than 15%, red cell distribution width (RDW) of more than 15%, and serum ferritin less than 30 μg/l.
After proper consent from parents/guardians of the study children, blood samples of the study children were sent for investigations. Complete blood count was estimated by an automated hematology analyzer XP series (Sysmex Kx-21; Chu-ku, Kobe, Japan) and serum ferritin by ELISA method (AcuBind Ferritin; Tosoh India Pvt Ltd, Mumbai, Maharashtra, India). Proper ethical and scientific committee approval was taken before conducting this research.
All data were collected, tabulated, and analyzed by the Statistical Package for the Social Sciences software, statistical package, version 18 (SPSS Inc., Chicago, Illinois, USA). Discrete variables were expressed as n (%) and were compared using χ2 tests. Continuous variables are expressed as mean ± SD and compared by means of the unpaired, two-sided t test. Adjusted odds ratios and 95% CIs were calculated. Statistical significance was set at a P value of less than 0.05. Univariate and multivariate analysis were done of the several variables which are taken as part of th study (e.g., age, sex, socioeconomic class, past or family history of epilepsy, etc.) and logistic regression for discrete variables was applied.
Results and observations
In this study, cases and controls were matched for parameters which could affect the incidence of simple febrile seizures. The comparison revealed no significant difference with P value of more than 0.05 for all parameters [Table 1].
Hematological parameters when compared between cases and controls also showed significant statistical significance. Mean value with SD of various hematological parameters in cases and controls were:
- Hemoglobin (g/dl) of 10.24 ± 1.0 and 11.45 ± 1.5 (P = 0.005)
- MCV (fl) of 70 ± 7.8 and 88.54 ± 6.81 (P ≤ 0.001)
- MCH (pg) of 20.23 ± 2.3 and 28.26 ± 2.6 (P = 0.008)
- MCHC (g/dl) of 28 ± 4.2 and 34 ± 3.5 (P = 0.04)
- RDW (%) of 15.8 ± 1.2 and 13.3 ± 2.1 (P = 0.021).
Total iron-binding capacity (μg/dl), transferrin saturation (%), and serum ferritin (μg/l) of cases and controls were 340 ± 34, 14.2 ± 1.2, 38 ± 10, and 230 ± 20, 16 ± 1.0, and 42 ± 12, respectively. The P values were also significant (P < 0.05) [Table 2].
|Table 2: Comparison of hematological parameters between cases and controls|
Click here to view
Iron deficiency anemia was recorded in 68 (42%) cases and 20 (12.5%) of the controls. Statistical comparison of frequency of iron deficiency anemia between cases and controls showed an odds ratio of 5.17 and significant difference with a P value of 0.0001 at CI of 2.9444 to 9.0915 as shown in [Table 3].
| Discussion|| |
Our study found that the mean age of the cases was 3.2 ± 1 years while for the control it was 3.6 ± 1.3 years and mean weight with an SD of 15.2 ± 2.3 in cases and of 16.4 ± 1.9 in controls. Similar results were found in other studies conducted by Pisacane et al., Vaswani et al., and Kumari et al.. This study revealed that iron deficiency anemia has a significant association with simple febrile seizures and prevalence of anemia is approximately more than five times in children who had simple febrile seizures than in children without simple febrile seizures. Thus, iron deficiency can be considered as a significant risk factor for the occurrence of simple febrile seizures. This finding is supported by the study of Kumari et al., who showed 63.6% of children who presented with simple febrile seizures had significant iron deficiency anemia with crude odds ratio of 5.34 (3.27–8.73). Similar results were shown by Pisacane et al.  with odds ratio of 3.3 (95% CI of 1.7–6.5). Sharma AK et al.  found that in children with febrile seizures there is almost twice higher prevalence of iron deficiency than controls. Sherjil et al.  showed 31.85% of cases had iron deficiency anemia with an odd ratio of 1.93. Literally all hematological parameters which were evaluated in our study for comparison with simple febrile seizures were significantly low in cases as compared with controls. Similar findings were found by Sharma and Sharma  who found that the mean serum ferritin level (ng/ml) was significantly low in cases (41.92 ± 20.37) as compared with controls (66.26 ± 26.40) and values of hemoglobin (g/dl), hematocrit (%), and MCV (fl) in children suffering from febrile seizures were significantly less than children in the control group. RDW (fl) in their study was also significantly high in the case group compared with the control group. Sherjil et al.  also showed significantly decreased levels of hemoglobin level, serum ferritin level, MCHC, and MCV in children with simple febrile seizures. Aziz et al.  also found that in their study mean hematocrit, red blood cells, MCV, MCH, MCHC, and RDW had statistically significant difference between the two groups (simple febrile seizure group vs. normal group).
To conclude, our study revealed significant association of iron deficiency anemia with simple febrile seizures. Thus, iron deficiency anemia should be considered as a risk factor which increases the incidence of simple febrile seizure.
We recommend evaluation for iron status of every child who present with simple febrile seizures and treat it, if iron deficiency is diagnosed such that the incidence of simple febrile seizures can be decreased.
The authors are highly thankful to the hospital administration and parents of the study children, who gave permission to conduct this research. The authors also thank senior and junior colleagues for their valuable support.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kliegman RM, Stanton BF, Geme JWSt, Schor NF. Nelson textbook of Pediatrics; 20th
South Asian edition; Reed Elsevier India Private Limited; 2016. Vol 3; Part XXVII; Chapter no. 590: 2823–2829.
Millichap JG, Millichap JJ. Role of viral infections in the etiology of febrile seizures. Pediatr Neurol 2006; 35
Holtzman D, Obana K, Olson J. Hyperthermia-induced seizures in the rat pup: a model for febrile convulsions in children. Science 1981; 213
Virta M Hurme M, Helminen M. Increased plasma levels of pro- and anti-inflammatory cytokines in patients with febrile seizures. Epilepsia 2002; 43
Kumari PL, Nair MK, Nair SM, Kailas L, Geetha S. Iron deficiency as a risk factor for simple febrile seizures-a case control study. Indian Pediatr 2011; 49
Amiri M, Farzin L, Moassesi ME, Sajadi F. Serum trace element levels in febrile convulsion. Biol Tr Elem Res 2010; 135
Fukahori M, Itoh M, Oomagari K, Kawasaki H. Zinc content in discrete hippocampal and amygdaloid areas of the epilepsy (El) mouse and normal mice. Brain Res 1988; 455
World Health Organization. Iron deficiency anaemia
. Geneva: Assessment, Prevention and Control. A Guide for Program Managers. WHO/NHD/013; 2001.
Pisacane A, Sansone R, Impagliazzo N, Coppola A, Rolando P, D'apuzzo A, et al
. Iron deficiency anaemia and febrile convulsions: case-control study in children under 2 years. BMJ 1996; 313
Vaswani RK, Dharaskar PG, Kulkarni S, Ghosh K. Iron deficiency as a risk factor for first febrile seizure. Indian Pediatr 2009; 47
Sharma AK, Sharma R. Evaluating the association between iron deficiency and simple febrile seizure in children aged 6 months to 5 years: a case control study. Int J ContempPediatr 2018; 5
Sherjil A, Saeed Z, Shehzad S, Amjad R. Iron deficiency anaemia – a risk factor for febrile seizures in children. J Ayub Med Coll Abbottabad 2010; 22
Aziz KT, Ahmed N, Nagi AG. Iron deficiency anaemia as risk factor for simple febrile seizures: a case control study. J Ayub Med Coll Abbottabad 2017; 29
[Table 1], [Table 2], [Table 3]