Prevalence and association of iron deficiency anaemia in febrile seizures a prospective observational study

 

 

Abstract              Background: Iron deficiency anemia and febrile seizure are two common conditions in children world wide as well as in our country. iron deficiency is known to cause neurological symptoms like behavioural changes, poor cognition and attention span thereby it may be associated with another common neurological condition in childhood like febrile seizure. Materials And Methods: Observational study , looking for the prevalence of iron deficiency anemia in cases of febrile seizures. A minimum sample size of 350 cases of typical febrile seizure in children in age group of 6 months to 60 months are taken with a prevalence of iron deficiency anemia in febrile seizure was around 31.85 % at a confidence interval of 95%. Results: Out of 350 children enrolled 131 (37.4%) were female and 219 (62.6%)were males. Out of the 350 children’s 107 (30.6%)were  found have associated iron deficiency anaemia, which included 64(59.8%) of male and 43 (40.2%) Of females. Peak incidence of Febrile Seizures found maximum  between  13 to 18 months(39.4%). Conclusion : low serum iron levels and the presence of anemia can serve as strengthening factors for the Febrile seizures in children. Therefore, ID(Iron deficiency) can be added to the list of risk factors for febrile convulsions. Accordingly, children with FSs are suggested to be monitored for diagnosis and treatment of IDA. Furthermore, it is advisable to prescribe iron supplements earlier and more carefully to children who have important and well-known risk factors for febrile convulsion, such as family history of febrile convulsion.

 

INTRODUCTION

Febrile convulsion (FC) is the most common disorder in the nervous system of children and 2-5% of the total number of (or 4.8 out of every 1000) children become affected every year.¹ Febrile convulsion is defined as convulsion resulting from fever. It occurs in children of 6 months to 6 (full six) years of age, is accompanied by fever higher than 38°C, and does not involve symptoms of central nervous system infections or any other background causes.¹ Risk factors of this disorder include history of convulsion or FC in the family, head injuries, mothers who smoke or consume alcoholic beverages, and high fevers.^2,3,4,5,6 Since a risk of FC is the probability of its subsequent development into convulsion and epilepsy, various studies have been carried out with the purpose of identifying correctable risk factors to reduce the prevalence of FC and, hence, of epilepsy and convulsion.

Aims and Objectives: To determine the relationship between iron deficiency anaemia and febrile seizures. To find out the incidence of anemia in febrile seizure in males and females. To identify the peak age group of febrile seizures.

 

MATERIALS AND METHODS

Febrile seizures will be associated with iron deficiency anemia in at least about 30% of cases.

Source of study: The proposed study is a hospital based prospective observational study consisting of infants and children aged between 6 months to 5 years. They will be evaluated at Department of Paediatrics, Ayaan institute of medical sciences including both OP and IP cases.

Study duration:  01.10.2019 TO 01.10.2020. Study Design: Observational study, looking for the prevalence of iron deficiency anemia in cases of febrile seizures. Sample Size: A minimum sample size of 350 cases of typical febrile seizure in children in age group of 6 months to 60 months are taken with a prevalence of iron deficiency anemia in febrile seizure was around 31.85 % at a confidence interval of 95%. Sample size calculation for the present study was based on the case control study done by Sherjil A, US saeed Z, Shehzed S. Amjed R in which it was found that “31.85% of cases (50 out of 157) had iron deficiency anaemia whereas, 19.6% of controls (30 out of 153) were found to have iron deficiency anaemia as revealed by low levels of haemoglobin level, serum ferritin level. Mean Corpuscular Haemoglobin Concentration and Mean Corpuscular Volume¹⁵. Odds ratio was 1.93.” It was found that a minimum sample size required is 323. This was calculated using sample size for frequency in population on OpenEpi, version 3, open source calculator –SSPropor. However I am taking a sample size of 350 for better validation of results.

Sampling Method: Simple random sampling.

Inclusion Criteria: Children with typical febrile seizure between 6 months and 5 years.

Exclusion Criteria: Children aged < 6 months and > 5years. Children presenting with atypical febrile seizures. Children presenting with afebrile seizures or those having any signs of CNS infection. Those children with history of birth asphyxia/developmental delay/epilepsy. Those children on Iron supplementation therapy. Very sick children. Children those fall into Grade III PEM category on IAP charts. Family h/o Epilepsy/mental retardation.

Statistical Methods: Descriptive statistics, frequencies and percentages, chi square, SPSS window.

 

RESULTS

This study is a hospital based prospective observational study which includes 350 children in the age group of 6m to 60m with typical Febrile seizures. Out of 350 children enrolled 131 (37.4%)were female and 219 (62.6%)were males. Out of the 350 children’s 107 (30.6%)were found have associated iron deficiency anaemia, which included 64(59.8%) of male and 43 (40.2%) Of females. Peak incidence of Febrile Seizures found maximum between 13 to 18 months(39.4%). And the Peak incidence of Febrile Seizures with Iron deficiency anaemia was found at 13m to 18 months and 25 to 36 months as 25.2% and 26.2% respectively. 1^st episode of Febrile seizures was found to occur maximally during the age group of 13m to 18 months (51.1%). From the above data I conclude that there is a strong association between febrile seizures and iron deficiency Anaemia. (P <0.001).

Table 1: IDA1

 

Table 2: IDA1 * sex Crosstabulation

 

Table 3: Chi-Square Tests

Table 4: IDA1 * Rage Crosstabulation

 Table 5: IDA1 * Rage Crosstabulation

 

Table 6: Chi-Square Tests

 

Table 7: Crosstab

 

Table 8: Crosstab

 

Table 9: Chi-Square Tests

 

Table 10

 

Table 11: Chi-Square Tests

 

Table 12: Episode * IDA1 Crosstabulation

 Table 13: Chi-Square Tests

 

Table 14

 

Table 15: Group Statistics

 

Table 16: Independent Samples Test

 

Table 17: Independent Samples Test

 

Table 18: Independent Samples Test

DISCUSSION

Iron deficiency anemia and febrile seizure are two common conditions in children worldwide as well as in our country. iron deficiency is known to cause neurological symptoms like behavioural changes, poor cognition and attention span. thereby it may be associated with another common neurological condition in childhood like febrile seizure. In the current study which is a hospital based prospective observational study where 350 children presented with typical febrile seizure in the age group of 6 months to 60 months were enrolled. out of which 131(37.5%) were females and 219(62.6%) were males. iron deficiency anemia was found to be associated with 30.6% of the subjects. Febrile seizure were found to be more prevalent in males (62.6%), in contrast in females(37.4%). Peak incidence of febrile seizure was found maximum (39.4%) at 13-18months. In accordance with our research, a Indian case control study by kumari et al. in 2012 suggested that highly significant association was found between iron deficiency and febrile seizure with crude odd’s ratio of 5.34 and adjusted odd’s ratio in the logistic regression analysis was 4.5with p<0.001.⁴ Also in another Indian study, by vaswani et al., in 2010 68% of cases were iron deficient compared to 30 % of controls indicating iron deficiency could be a potential risk factor for febrile seizure in children.⁵ A study by pisacane et al. Reported that anemia in their case group (30%) was higher than in hospital control group (14%) and healthy group(12%).⁰⁶ A study by Ur-Rahman and Billoo on 30 children with febrile convulsion and 30 children with other febrile illness indicated that iron deficiency anemia in their case group were significantly more common than in controls.⁷ A Kenyan case control study as well as the meta analysis of 8 case control studies that have examined the relationship between febrile seizure and iron deficiency, suggested that iron deficiency may be associated with an increased risk of febrile seizure in children.⁸

Iron deficiency and iron deficiency anemia may play an important role in inducing seizures from the following mechanisms:⁹

Decrease in GABA inhibitory neurotransmitter due to change in its metabolism. Reduction of enzymes such as monoamine and aldehyde oxidases. Impairment in oxygenation and energy metabolism of the brain.

In a study conducted in Thailand, the rate of thalassemic children with febrile convulsion was reported as being 4.4% less than the general population of children. the researchers suggested that it might be due to higher levels and the role of iron in brain metabolism, which leads to reduced occurrence of febrile convulsion in those children. This study of course could simply assess the role of increasing iron in relation to febrile seizure and cannot be an appropriate scale to measure iron deficiency anemia and febrile convulsion. On the other hand low risk of febrile convulsion in the patients could be due to several other clinical condition that they may have.¹⁰ On the other hand, some studies have reported findings that are not similar to the present study. for instance in Kobrinsky et al.’s study the febrile convulsion group suffered less from iron deficiency and it was concluded that iron deficiency could have a protective effect against febrile seizure.¹¹ In a study by Bidabadi , iron deficiency in febrile convulsion group (44%) was less than in the control group (48%), but since there was no significance difference , the protective effect of iron deficiency against febrile convulsion was not confirmed.¹² The possible explanation for these discrepancies are differences in age, nutritional habits, geographical area, sample size, general economic status and diagnostic criterion. Ferritin is an acute phase reactant and is non specific in any febrile disease.¹³ this is confirmed by the higher plasma ferritin levels in the patient groups than in the healthy group. fever can cause the lack of difference in ferritin levels between two patient groups. in any case, use of plasma ferritin cannot simply be an efficient criterion for the diagnosis of iron deficiency in febrile children.

 

CONCLUSION

Our findings suggest that low serum iron levels and the presence of anemia can serve as strengthening factors for the Febrile seizures in children. Therefore, ID(Iron deficiency) can be added to the list of risk factors for febrile convulsions. Accordingly, children with FSs are suggested to be monitored for diagnosis and treatment of IDA. Furthermore, it is advisable to prescribe iron supplements earlier and more carefully to children who have important and well known risk factors for febrile convulsion, such as family history of febrile convulsion. It would be worthwhile to conduct a study to follow up children with ID, who are stricken by febrile convulsions after the treatment of ID, in terms of the recurrence rate of febrile convulsion.

 

REFERENCES

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10. Auvichayapat P, Auvichayapat N, Jedsrisuparp A, Thinkhamrop B, Sriroj S, Piyakulmala T,et al. Incidence of Febrile Seizures in Thalassemic Patients.J Med Assoc Thai 2004:87(8):970-3.
11. Kobrinsky NL, Yager JY, Cheang MS, Yatscoff RW, Tenenbein M. Does iron deficiency raise the seizure threshold? J Child Neurol. 1995 Mar;10(2):105-9.
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