Febrile seizures are one of the most common neurologic disorders in the pediatric age group, affecting two to five percent of children between 6 months and 5 years of age with a peak incidence between 12 to 18 months [1, 2] The exact cause of the febrile seizure is not known, but several environmental and genetic factors have been implicated in etiology. Febrile seizures often occur in the context of roseola, herpes simplex, otitis media, shigella, or similar infections [3]. Many independent risk factors such as age, gender, genetic factors, fever, duration of seizure, family history, developmental history, recurrent seizures, perinatal exposure to drugs, history of maternal smoking, and alcohol consumption during pregnancy have been studied as potential risk factors for recurrent febrile seizures [4, 5] Iron Deficiency anemia was also studied as an etiological factor and found to be associated with increased incidence of febrile seizures [6, 7] Also, the maximum age of febrile seizure occurrence in second-year overlaps with the maximum prevalence of Iron Deficiency Anemia (IDA) in children.

The most common micronutrient deficiency worldwide (30%) is iron deficiency anemia, and in developing countries (50%), the prevalence is much higher. IDA was more prevalent in the 6–24 months age group [8]. As it is a preventable cause, the incidence of febrile fits can be decreased by treating nutritional anemia with diet and iron supplements [9]. The seizure threshold of a child may be altered by iron deficiency, as it reduces the metabolism of a few neurotransmitters, such as aldehyde oxidase and monoamine [10, 11] There is also a decrease in neuronal metabolic activity in iron deficiency anemia.18 Thus, iron deficiency, which is an easily correctable condition, is also postulated as a risk factor for febrile seizures in children.19 Considering the age of prevalence of IDA and FS, which are the same, the role of iron in the metabolism of neurotransmitters (such as GABA and serotonin) and some enzymes (such as monoaminoxidase and aldehyde), a relationship between IDA and FS is probable. The association between febrile seizures and iron-deficiency anemia has been scrutinized worldwide. The majority of studies have established the role of iron deficiency anemia as a leading risk factor for febrile seizures [12]. Whereas few have found no association between iron deficiency anemia and acute seizures [13]. Therefore, the present study was conducted to determine the association between iron deficiency anemia and febrile seizures among children under the age of 5 years

This cross-sectional study was done in the Department of Pediatrics, Tertiary Care Hospital, Nalgonda. Institutional Ethical approval was obtained for the study. Pretest counseling was given to parents/guardians in the vernacular language. Written and informed consent was taken from parents of children who participated in the present study.

Sample size calculation:  Based on the previous studies, the prevalence of febrile seizures was taken at 2%, Estimated prevalence (p) = 2% Confidence interval (CI) = 95%. [Zα/2 is the standard normal deviation, which is 1.96 at 95% confidence interval] Absolute precision (d) = 4%. Using the standard formula for proportion = [(Zα/2)2 × p × q] / d2

Sample size (n) = (Zα/2)2 × p × (1-p) / d2

= (1.96×1.96) ×2×98 / 4 x 4

= 752.95 / 16 = 47.05

The final sample size for the present study was rounded to 50.

Inclusion criteria

1. Age 6 – 60 months.
2. Presenting with febrile seizures including simple and complex febrile seizures
3. Febrile seizures including both 1st episode and recurrent episodes
4. Parents of children who gave consent for the study.

Exclusion Criteria:

1. Any chronic systemic illness (Cardiac, Renal, Metabolic, Malignancy, Rheumatological).
2. Neurodevelopmental delay
3. Previous afebrile seizures
4. Acute CNS infection
5. Children on iron therapy

After selecting the case based on the inclusion and exclusion criteria. A complete detailed history was taken and a general physical examination was done for all patients. Data was collected using a Predesigned, semi-structured questionnaire which includes age, sex, presenting complaint type and duration of seizures, socioeconomic classes, and comorbid illness (RTI, GIT infection, UTI, skin infections, others). After history taking and clinical examination, blood samples were collected from the patients for Hb, MCV, MCH, and serum ferritin. Based on lab investigations like complete blood picture, serum ferritin levels, and peripheral blood smear diagnosis of iron deficiency anemia was confirmed. Iron deficiency anemia had been considered as Haemoglobin <11.0 g/dL and mean corpuscular volume <70 μm3, MCH<25 pg/l, MCHC <30 g/dl, Serum ferritin <12 μg/L, (in the presence of infection <30 and in some cases in acute infection with raised CRP the values were much higher and in those the level of serum ferritin was not considered).

Statistical analysis

 All the available data was segregated, refined, and uploaded to an MS Excel spreadsheet and analyzed by SPSS version 22 in Windows format.  Continuous variables were reported as mean ± standard deviation (SD) while categorical variables were expressed as absolute values and percentages. A chi-square test and unpaired t-test were applied to find the significant difference between iron deficiency anemia and non-iron deficiency anemia in febrile seizure cases. A P-value less than 0.05 was considered statistically significant.

The majority of the children 44% in the study group belonged to the 13 – 24-month age group, followed by 34% in the 25 – 60-month age group. 22% of children belonged to the 6 – 12-month age group. The mean age of the study population was 23.5 ± 13.4 months with an age range of 7 – 56 months; 62% of the children were male and 38% were female. The gender ratio male to female in the study was 1.6:1. The mean duration of fever in the study group was 2.5 ± 1.6 days (range, 1–7 days). In 32% of children, the duration of fever was one day, followed by two days in 30% of children. In 18% of the cases, the duration of fever was > 3 days (Table 1).

Febrile seizures among 54% of children occur during the first day of a child's fever. Among 24% of children, the seizure onset was on the second day of fever, and in 22% it was on the third or more days of fever. At the time of admission, 8% had a temperature above 102°c, 42% had 101°c – 102°c and 40% had 99°c – 100°c. The body temperature was normal in 10% of children.

                                 *Significant

The most common type of febrile seizure in the study group was a simple seizure (94%) given in Table 3. In the present study, 6% of the patients had complex febrile seizures. The most common cause of febrile seizures in children was LRTI (45.7%), followed by acute gastroenteritis (20%), and UTRI (14.3%). Other common causes of febrile seizures in the children were ASOM (8.6%), UTI (8.6%), and PIMS (2.9%).

The mean hemoglobin of children in the present study was 11.17 ± 1.67 gm/dl. Based on the WHO cut-off values, anemia was present in 42% of cases (Table 4). The mean serum ferritin in the study population was 42.30 ± 25.39 µg/l. The mean MCV was 71.34 ± 5.47. The mean MCH in the study population was 24.29 ± 2.33 µg/dl. Among 50 febrile seizure cases, hemoglobin level was then 11g/dl in 42%, mean corpuscular volume < 70 fl in 36%, serum ferritin was low in 36%, and mean corpuscular hemoglobin <25 Pg/l in 48% of cases. Among 50 febrile seizure cases, 54% had iron deficiency anemia.

Among the 27 iron deficiency anemia cases, 44.5% belonged to 13 – 24 months, and 29.6% belonged to 6 – 12 months. No statistically significant association was found between age and iron deficiency anemia in febrile seizure cases. Among the 27 iron deficiency anemia cases, 63% were male and 37% were female. There was no statistically significant association between sex and iron deficiency anemia in febrile seizure cases. Among children with a history of febrile seizures, 84.6% had iron deficiency anemia, and among children with no history of febrile seizures, 43.2% had iron deficiency anemia. There was a statistically significant association between iron deficiency anemia and a history of febrile seizures.

In 54% of children, the duration of febrile seizure was ≤ 5 min, and in 32% it was 6 – 10 min. The mean duration of febrile seizure in the present study was 7.2 ± 3.8 mins (Table 5). There was a history of febrile seizures in 26% of children. In 2 cases there were 3 or more episodes of febrile seizures in the past. Out of 50 children, a family history of febrile seizures was present in 10% of cases.

Febrile seizures (FS), are usually benign and a common cause of childhood convulsion however, it is a source of significant parental concern. Iron deficiency anemia has been increasingly investigated recently as a potential risk factor for febrile seizures. Iron plays an important role in neurotransmitter metabolism, myelination, and brain energy modulation. This cross-sectional study evaluated 50 children aged 6 – 60 months presenting with FS and admitted to our tertiary care hospital. The mean age of the cohort at the onset of seizure was 23.5 ± 13.4 months, and most of the cases (44%) were found to occur between the ages of 13 – 24 months. These findings were in concordance with studies of Kumar et al [14], Sharif et al. [15], and Shah et al. [16] where they found a similar distribution by age in cases of FS. The results of our study showed male preponderance (62%) which was similar to findings reported in other several studies [17, 18], Although few of the studies have reported female dominance [19] this could be because of the distribution of cases and geographical locations and pattern of referral to tertiary care centers which may not reflect the true incidence.  The mean duration of fever before the development of seizures was 2.5 ± 1.6 days and most of the seizures occurred within the duration of 24 hours of onset of fever (54%) cases. Similar findings have been reported by Kumar et al. [18] and Shah et al. [16] where the occurrence of seizures was within 24 hours of fever. In this study, we found that Simple febrile seizures were predominant (94%) cases, which is in agreement with the findings of Shah G. et al. [16].

The common cause of fever in this study was respiratory tract infection followed by gastroenteritis. A similar picture has been reported by Kumar et al. Jang et al. [20] and Ghasemi et al. [13] in their respective studies. The average duration of seizure was 7.2 ± 3.8 minutes with 54% of cases lasting for ≤ 5 minutes. Ghosal et al. [21] and Shah et al. [16] have shown similar findings in their studies. In our study, the evaluation of history shows that 26% of cases had a history of febrile seizures and family history shows that 10% had a family history of febrile seizures similar findings have been reported by other similar studies in this field [15, 16]. The mean hemoglobin concentration in our cases was 11.17 ± 1.67 g/dL, and 42% of children were anemic. Similar observations have been reported by Addil et al. [17] and Sultan et al. [22]. The mean corpuscular volume in the cases was (71.34 ± 5.47 fl), and mean corpuscular hemoglobin (24.29 ± 2.33 pg), and serum ferritin (42.30 ± 25.39 µg/L) were consistent with other studies [20, 23]. We found that 54% of FS cases had iron deficiency anemia similar to the finding reported by Shaik et al. [24] and Sultan et al. [22] they observed higher odds of FS in anemic children as compared to normal. However, Sausan et al. [25] and Sadeghzadeh et al. [26] did not report such findings which shows that it remains an unresolved controversy. The study revealed a statistically significant correlation between IDA and past FS history along with seizure duration even though no association emerged due to age gender or seizure type. This data was similar to the findings published by Shah G et al. [16] and Saha AK et al. [27]. The research findings indicate that patients with IDA tend to experience chronic seizures and develop recurring FS episodes thus supporting the IDA-FS intensity relationship. The study results showed that IDA affected more than half of the patients with FS. Further research needs to be conducted through multicentric studies to prove a link between iron deficiency and the pathophysiology of FS.

This study found a high prevalence (54%) of iron deficiency anemia among children with febrile seizures. This suggests that a potential association between the two may exist. While no significant relationship was observed with age, gender, or seizure type, iron deficiency was significantly associated with longer seizure duration and a history of previous febrile seizures. These findings support the hypothesis that iron deficiency may influence seizure characteristics. Routine screening and correction of iron deficiency in young children may be beneficial in reducing the severity and recurrence of febrile seizures. Further large-scale studies are recommended to validate these observations.

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