mmj_37_19R8

Original article  1

1 1
2
Association of iron deficiency anemia with simple febrile 2
3 seizures: a hospital‑based observational case–control study 3
4
AQ7 Jehangir A. Bhata, Sajad A. Sheikhb, Zubair A. Wanic, Sami U. Bhatd, 4
5 5
AQ1 Roshan Araa
6 6
7 7
8
a
Department of Pediatrics, Kurji Holy Objectives 8
Family Hospital, Patna, Bihar,bDepartment To reveal the association of iron deficiency anemia with simple febrile seizures.
9 of Gastroenterology, Vikas Hospital Pvt 9
Ltd, Najafgarh, New Delhi, cDepartment of
Background
10 Iron deficiency anemia has aa defined role in a variety of neurological and psychological 10
Pediatrics, Government Medical College,
11 Srinagar, Jammu and Kashmir, dSchool problems in children such as stroke, behavioral, and cognitive problems. Therefore, it is 11
12 of Chemistry, Jiwaji University, Gwalior, hypothesized that iron deficiency anemia may have a role in febrile seizures. 12
Madhya Pradesh, India
13 Patients and methods 13
AQ2
14 Correspondence to Jehangir A. Bhat, MBBS, It was a hospital‑based observational case–control study conducted on 320 children of age
14
DCH, DNB, Department of Pediatric, Kurji group 6–59 months. Children were divided into groups. Cases (160) who presented with simple
15 Holy Family Hospital, Patna, Bihar, India
febrile seizures and controls (160) who had fever of short duration without any type of seizure
15
e‑mail: ajaalam333@gmail.com
16 or abnormal body movement. At the time of presentation to hospital, venous blood sample 16
17 Received 09 February 2019 for routine investigations along with complete blood count of all children included in study 17
AQ3
18
Accepted ???
were sent to laboratory. All data were tabulated and analyzed with relevant statistical tests. 18
19 Menoufia Medical Journal 2019, XX:1–4 Results 19
Iron deficiency anemia is prevalent more (nearly > 5 times) in children who has simple febrile
20 20
seizures than in normal children. Thus, evaluation for iron deficiency should be done in every
21 child who present with simple febrile seizure. 21
22 Conclusion 22
23 Iron deficiency was recorded in 42 and 12.5% of cases and controls, respectively. Statistically 23
24 significant association was seen between iron deficiency anemia and simple febrile 24
seizures (P = 0.001) with odds ratio of 5.139. All hematological parameters which define iron
25 25
deficiency anemia were low and statistically significant in cases as compared to controls.
26 26
27 27
Keywords:
28 complete blood count, hematological parameters, iron deficiency anemia, odds ratio, simple 28
29 febrile seizure 29
30 30
Menoufia Med J XX:1–4
31 31
© 2019 Faculty of Medicine, Menoufia University
32 1110‑2098 32
33 33
34 34
35 than 15  min, reoccurs within 24  h, and can be focal 35
Introduction
36 or generalized with postictal neurological deficit like 36
Brain consists of nerve cells that usually communicate
37 Todd’s palsy or with prior neurological deficit. Various 37
with each other through electrical activity, thus,
38 factors have been described in the pathophysiology of 38
39 controlling and regulating all voluntary and febrile seizures such as: 39
40 involuntary responses in the body. When region(s) of (1) Infections like bacterial and viral [2] 40
41 the brain receives a burst of abnormal electrical signals (2) Temperature susceptibility of immature brain [3] 41
42 that temporarily interrupt the normal electrical brain (3) Interleukins, circulating toxins association [4] 42
43 function, a seizure occurs. Transient occurrence of signs (4) Micronutrient deficiency and iron deficiency [5]. 43
44 and/or symptoms resulting from abnormal excessive or 44
45 synchronous neuronal activity in the brain is defined Role of micronutrients such as copper, zinc, 45
46 as a seizure. Febrile seizures are the seizures which are magnesium, and selenium [6] have been described 46
47 associated with fever of above 38°C  (100.4 F) which in association with febrile seizures. Micronutrients 47
48 occur above 6 and below 60  months of age, in the appear to play a vital role by their ability to modulate 48
49 absence of any central nervous infections, metabolic neurotransmission by acting on ion channels as well 49
50 disturbances, and any prior afebrile seizures  [1]. as coenzyme activity  [7]. Extensive research is going 50
51 Febrile seizures are divided into simple/typical and on to discover new risk factors which increase the 51
52 complex/atypical febrile seizures. Simple febrile 52
53 seizures are usually generalized tonic clonic type, lasting This is an open access journal, and articles are distributed under the terms 53
54 of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 54
less than or equal to than 15 min and does not reoccur License, which allows others to remix, tweak, and build upon the work
55 within 24 h in neurological and psychomotor normal non‑commercially, as long as appropriate credit is given and the new
55
56 children  [2,3]. Complex febrile seizures last more creations are licensed under the identical terms. 56

1110-2098 © 2019 Faculty of Medicine, Menoufia University DOI: 10.4103/mmj.mmj_37_19

 2  Menoufia Medical Journal, Volume XX | Number XX | Month 2019

1 incidence of febrile seizures like 25 hydroxy vitamin D, Proper ethical and scientific committee approval was 1
2 iron status, vitamin B6, etc. taken before conducting this research. 2
3 3
4 The aim of our study was to find the association of 4
5 iron deficiency with simple febrile seizures, so that Statistical analysis 5
6 by modifying the iron status of children, incidence of All data were collected, tabulated, and analyzed by the 6
7 simple febrile seizures can be reduced. Statistical Package for the Social Sciences software, 7
8 statistical package, version  18  (SPSS Inc., Chicago, 8
9 Illinois, USA). Discrete variables were expressed as n (%) 9
10 and were compared using χ2 tests. Continuous variables 10
11 Patients and methods are expressed as mean ± SD and compared by means of 11
12 It was a prospective observational case–control study the unpaired, two‑sided t test. Adjusted odds ratios and 12
13 conducted on 320 children of age group 7–59 months 95% CIs were calculated. Statistical significance was set 13
14 in the City Max Hospital and Research Centre, Tohana, at a P value of less than 0.05. Univariate and multivariate 14
15 Haryana for a period of 2 years from May 2013 to April analysis were done of the several variables which are 15
16 2015.One hundred and sixty children who presented taken as part of th study (e.g., age, sex, socioeconomic 16
17 with simple febrile convulsion were considered for this class, past or family history of epilepsy, etc.) and logistic 17
18 study and 160 children for concurrent controls were regression for discrete variables was applied. 18
19 selected from the same setting of the same age group 19
20 who present with short duration of fever  (<3  days) 20
Results and observations
21 but without seizures. Simple febrile seizures were 21
In this study, cases and controls were matched for
22 defined as per the American Academy of Pediatrics 22
parameters which could affect the incidence of simple
23 definition [1]  [febrile seizures are the seizures which 23
febrile seizures. The comparison revealed no significant
24 are associated with fever of above 38°C  (100.4 F) 24
difference with P  value of more than 0.05 for all
25 which occur above 6 and below 60 months of age, in 25
parameters (Table 1).
26 the absence of any central nervous infections, metabolic 26
27 disturbances, and any prior afebrile seizures]. 27
Hematological parameters when compared between
28 28
cases and controls also showed significant statistical
29 Children of the above‑mentioned age group who 29
significance. Mean value with SD of various
30 presented with simple febrile seizure were included in 30
hematological parameters in cases and controls were:
31 this study. 31
• Hemoglobin  (g/dl) of 10.24  ±  1.0 and
32 32
11.45 ± 1.5 (P = 0.005)
33 Children having cerebral palsy, seizure disorder, chronic 33
• MCV (fl) of 70 ± 7.8 and 88.54 ± 6.81 (P ≤ 0.001)
34 diseases, dysmorphic and syndromic features, on 34
• MCH  (pg) of 20.23  ±  2.3 and
35 anticonvulsants, chronic diarrhea, and metabolic disorders 35
28.26 ± 2.6 (P = 0.008)
36 were excluded. Children who presented with electrolyte 36
• MCHC (g/dl) of 28 ± 4.2 and 34 ± 3.5 (P = 0.04)
37 imbalance  (sodium, calcium, etc.), hypoglycemia, 37
• RDW (%) of 15.8 ± 1.2 and 13.3 ± 2.1 (P = 0.021).
38 meningitis, and encephalitis were also excluded. 38
39 39
Total iron‑binding capacity  (μg/dl), transferrin
40 Iron deficiency was defined as per the WHO saturation (%), and serum ferritin (μg/l) of cases and 40
41 criteria  [8]: hemoglobin less than 11  g/dl, mean controls were 340 ± 34, 14.2 ± 1.2, 38 ± 10, and 230 ± 20,
41
42 corpuscular volume  (MCV) less than 72 fl, mean 16 ± 1.0, and 42 ± 12, respectively. The P values were
42
43 corpuscular hemoglobin (MCH) less than 25 pg, mean 43
also significant (P < 0.05) (Table 2).
44 corpuscular hemoglobin concentration  (MCHC) less 44
45 than 30  g/dl, total iron‑binding capacity more than Iron deficiency anemia was recorded in 68 (42%) cases 45
46 210 μg/dl, transferrin saturation less than 15%, red and 20 (12.5%) of the controls. Statistical comparison 46
47 cell distribution width (RDW) of more than 15%, and of frequency of iron deficiency anemia between 47
48 serum ferritin less than 30 μg/l. cases and controls showed an odds ratio of 5.17 and 48
49 significant difference with a P value of 0.0001 at CI of 49
50 After proper consent from parents/guardians of the 2.9444 to 9.0915 as shown in Table 3. 50
51 study children, blood samples of the study children 51
52 were sent for investigations. Complete blood count 52
53 was estimated by an automated hematology analyzer 53
54 XP series (Sysmex Kx‑21; Chu‑ku, Kobe, Japan) and Discussion 54
55 serum ferritin by ELISA method  (AcuBind Ferritin; Our study found that the mean age of the cases was 55
56 Tosoh India Pvt Ltd, Mumbai, Maharashtra, India). 3.2 ± 1 years while for the control it was 3.6 ± 1.3 years 56
 Iron deficiency and simple febrile seizures Bhat et al.  3

1 Table 1 Comparison of demographic profile of study children (mean±SD) 1

2 Parameters Cases (n=160) (95% CI) Controls (n=160) (95% CI) P 2
3 Age (years) 3.2±1.2 (3.01‑3.38) 3.6±1.3 (3.39‑3.80) 0.987 3
Weight (kg) 15.2±2.3 (14.84‑15.55) 16.4±1.9 (16.10‑16.69 0.076
4 4
Height (cm) 90.3±12.3 (88.38‑92.21 91±11.7 (89.18‑92.81) 0.675
5 5
Previous history of febrile seizures 28 (17.5) 0
6 6
Family history of febrile seizure 24 (15) 7 (4.37) 0.432
7 Family history of epilepsy 12 (7.5) 4 (2.5) 0.432
7
8 Vaccination status (special focus on Haemophilus influenza) 126 (78.75) 132 (82.5) 0.087 8
9 Data are presented as mean±SD and n (%). CI, confidence interval.
9
10 10
11 11
Table 2 Comparison of hematological parameters between cases and controls
12 Parameters Cases (n=160) 95% CI Controls (n=160) 95% CI P
12
13 Hemoglobin (g/dl) 10.24±1.0 10.08‑10.39 11.45±1.5 11.21‑11.68 0.005* 13
14 MCV (fl) 70±7.8 68.79‑71.20 88±5.4 87.1‑88.83 <0.001* 14
15 MCH (pg) 20±2.3 19.65‑20.35 28±2.6 27.59‑28.40 0.008* 15
16 MCHC (g/dl) 28±4.2 27.38‑28.61 34±3.5 33.45‑34.54 0.04* 16
17 RDW (%) 15.8±1.2 15.61‑15.98 13.3±2.1 12.97‑13.62 0.021* 17
18 TIBC (μg/dl) 340±34 334.7‑345.26 230±20 226.9‑233 0.003* 18
19 Transferrin saturation (%) 14.2±1.2 14.01‑14.38 16±1.0 15.84‑16.15 <0.001* 19
Serum ferritin (μg/l) 38±10 36.45‑39.54 42±12 40.14‑43.85 0.008*
20 20
21 Data are presented as mean±SD. CI, confidence interval; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin 21
concentration; MCV, mean corpuscular volume; RDW, red cell distribution width; TIBC, total iron‑binding capacity. *Significant P.
22 22
23 23
24
Table 3 Prevalence of iron deficiency anemia among cases found by Sharma and Sharma [11] who found that 24
and controls
25 the mean serum ferritin level (ng/ml) was significantly 25
Iron deficiency anemia Present Absent
26 low in cases  (41.92  ±  20.37) as compared with 26
Cases 68 (42.5) 92 (57.5)
27 Controls 20 (12.5) 140 (87.5)
controls (66.26 ± 26.40) and values of hemoglobin (g/dl), 27
28 Odds ratio 5.1739 hematocrit  (%), and MCV  (fl) in children suffering 28
29 95% confidence interval 2.9444‑9.0915 from febrile seizures were significantly less than 29
30 Significance level P<0.0001* children in the control group. RDW (fl) in their study 30
31 Data are presented as n (%). *Significant P. was also significantly high in the case group compared 31
32 with the control group. Sherjil et  al. [12] also showed 32
33 and mean weight with an SD of 15.2 ± 2.3 in cases and significantly decreased levels of hemoglobin level, 33
34 of 16.4 ± 1.9 in controls. Similar results were found in serum ferritin level, MCHC, and MCV in children 34
35 other studies conducted by Pisacane et al. [9], Vaswani with simple febrile seizures. Aziz et al. [13] also found 35
36 et  al.  [10], and Kumari et  al.  [5]. This study revealed that in their study mean hematocrit, red blood cells, 36
37 that iron deficiency anemia has a significant association MCV, MCH, MCHC, and RDW had statistically 37
38 with simple febrile seizures and prevalence of anemia is significant difference between the two groups 38
39 approximately more than five times in children who had (simple febrile seizure group vs. normal group). 39
40 simple febrile seizures than in children without simple 40
41 febrile seizures. Thus, iron deficiency can be considered To conclude, our study revealed significant association 41
42 as a significant risk factor for the occurrence of simple of iron deficiency anemia with simple febrile seizures. 42
43 febrile seizures. This finding is supported by the study of Thus, iron deficiency anemia should be considered as 43
44 Kumari et al. [5], who showed 63.6% of children who a risk factor which increases the incidence of simple 44
45 presented with simple febrile seizures had significant febrile seizure. 45
46 iron deficiency anemia with crude odds ratio of 46
47 5.34 (3.27–8.73). Similar results were shown by Pisacane 47
Recommendations
48 et  al. [9] with odds ratio of 3.3 (95% CI of 1.7–6.5). 48
We recommend evaluation for iron status of every child
49
AQ4 Dawn  et  al. [11] found that in children with febrile 49
who present with simple febrile seizures and treat it, if
50 seizures there is almost twice higher prevalence of 50
iron deficiency is diagnosed such that the incidence of
51 iron deficiency than controls. Sherjil et al. [12] showed 51
simple febrile seizures can be decreased.
52 31.85% of cases had iron deficiency anemia with an 52
53 odd ratio of 1.93. Literally all hematological parameters 53
54 which were evaluated in our study for comparison Acknowledgements 54
55 with simple febrile seizures were significantly low in The authors are highly thankful to the hospital 55
56 cases as compared with controls. Similar findings were administration and parents of the study children, who 56
 4  Menoufia Medical Journal, Volume XX | Number XX | Month 2019

1 gave permission to conduct this research. The authors 6 Amiri M, Farzin L, Moassesi ME, Sajadi F. Serum trace element levels in 1
febrile convulsion. Biol Tr Elem Res 2010; 135:38–44.
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A, et al. Iron deficiency anaemia and febrile convulsions: case‑control
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study in children under 2 years. BMJ 1996; 313:343.
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13 12 Sherjil  A, Saeed  Z, Shehzad  S, Amjad  R. Iron deficiency anaemia  –  a 13
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