Febrile seizures are the most common type of seizure disorder in childhood, affecting 2–5% of children aged 6 months to 5 years [1]. They are defined by the International League Against Epilepsy (ILAE) as seizures occurring in association with fever (temperature ≥38°C) in the absence of central nervous system infection, metabolic disturbance, or prior afebrile seizures [2]. Febrile seizures are broadly classified into simple (generalized, lasting less than 15 minutes, and not recurring within 24 hours) and complex (focal, prolonged, or recurrent within 24 hours) [3].

The etiology of febrile seizures is multifactorial, with genetic predisposition, environmental triggers, and biochemical factors playing significant roles [4]. Iron deficiency has been proposed as one of the modifiable risk factors. Iron is essential for myelination, neurotransmitter synthesis (dopamine, serotonin, γ-aminobutyric acid), and oxygen transport to the brain [5]. Deficiency may lower the seizure threshold by impairing neurotransmission and cerebral oxygenation [6].

Serum ferritin, an intracellular iron storage protein, reflects total body iron stores and is considered the most sensitive laboratory indicator of iron deficiency [7]. However, ferritin is also an acute-phase reactant and can be elevated in infections and inflammation, complicating its interpretation in febrile illnesses [8]. Several studies have evaluated the relationship between serum ferritin and febrile seizures, but the results have been inconsistent — some report significantly lower ferritin levels in febrile seizure patients compared to febrile controls [9,10], while others find no such association [11].

Given the potential implications for prevention and management, further exploration in diverse populations is warranted. This study aims to determine the association between serum ferritin levels and febrile seizures in children aged 6 months to 5 years, and to assess whether ferritin levels differ with seizure type and duration.

MATERIALS AND METHODS

Study Design and Setting

This hospital-based case–control study was conducted in the Department of Pediatrics at Yadgir Institute of Medical Sciences, Yadgir, over five months from April 2025 to August 31, 2025. The study aimed to evaluate the association between serum ferritin levels and febrile seizures in children.

Study Population

A total of 50 children aged 6 months to 5 years were enrolled, comprising 25 cases and 25 controls.

• Cases: Children presenting with febrile seizures (simple or complex) as per the International League Against Epilepsy (ILAE) definition, i.e., a seizure accompanied by fever (≥38°C) without evidence of intracranial infection, metabolic disturbance, or history of afebrile seizures.
• Controls: Age- and sex-matched febrile children without seizures, attending the outpatient department or admitted for febrile illness during the same period.

Inclusion Criteria

Cases:

1. Children aged 6 months–5 years with a first or recurrent febrile seizure.
2. Fever onset within 24 hours of seizure episode.

Controls:

1. Children aged 6 months–5 years with febrile illness but no seizure history.

Exclusion Criteria (for both groups)

1. Evidence of central nervous system infection (meningitis, encephalitis).
2. Known neurological disorders or developmental delay.
3. Chronic systemic illness (e.g., thalassemia, chronic kidney disease).
4. Children already on iron supplementation or diagnosed with iron deficiency anemia under treatment.
5. Recent blood transfusion (within 3 months).

Sample Size and Sampling Technique

The sample size was fixed at 50 children, with 25 in each group, based on feasibility and study duration. Cases were selected consecutively from pediatric emergency/admission units, while controls were selected from febrile children visiting the outpatient department, matched for age (±6 months) and gender.

Data Collection

After obtaining written informed consent from parents/guardians, a detailed clinical history was recorded, including:

• Demographic details (age, sex)
• Presenting complaints
• Fever duration and grade
• Seizure characteristics (type, duration, number of episodes)
• Past medical history

A thorough general and systemic examination was performed.

Laboratory Investigations

Blood samples (3 mL) were collected under aseptic precautions within 24 hours of admission for:

1. Serum ferritin – measured using an enzyme-linked immunosorbent assay (ELISA) method.
2. Complete blood count – for hemoglobin, hematocrit, mean corpuscular volume (MCV), and red cell indices.
3. C-reactive protein (CRP) – to account for the acute phase reaction influence on ferritin levels.

All laboratory analyses were conducted in the institutional central laboratory, following standard operating procedures.

Statistical Analysis

Data were entered into Microsoft Excel and analyzed using Statistical Package for the Social Sciences (SPSS) version 21.1. Continuous variables were expressed as mean ± standard deviation (SD) and compared using Student’s t-test. Categorical variables were presented as frequencies and percentages, and compared using Chi-square or Fisher’s exact test. A p-value of <0.05 was considered statistically significant.

RESULTS AND OBSERVATIONS

Table 1: Age and Gender Distribution

Table 2: Fever Profile

Table 3: Type of Febrile Seizure in Cases

Table 4: Recurrence of Febrile Seizures

Table 5: Serum Ferritin Levels in Cases and Controls

Table 6: Hematological Parameters

Table 7: Relationship Between Serum Ferritin Levels and Seizure Type

Table 8: Relationship Between Serum Ferritin Levels and Seizure Duration

DISCUSSION

In this hospital-based case–control study, we observed that children with febrile seizures had significantly lower mean serum ferritin levels compared to age- and sex-matched febrile controls without seizures (48.6 ± 18.4 ng/mL vs. 92.3 ± 25.7 ng/mL, p < 0.001). Low ferritin levels (<30 ng/mL) were found in 24% of cases, while none of the controls had ferritin below this threshold. These findings suggest that reduced iron stores may be associated with an increased risk of febrile seizures.

Our results are consistent with several previous studies. Kumari et al. [9] and Naveed-ur-Rehman et al. [10] both reported significantly lower ferritin levels in febrile seizure cases compared to controls, supporting the hypothesis that iron deficiency lowers the seizure threshold. The biological plausibility lies in iron’s role in myelination and neurotransmitter synthesis — deficiency may alter neuronal excitability, predisposing to seizures [5,6].

We also found that ferritin levels were significantly lower in children with complex febrile seizures compared to simple seizures (39.2 ± 19.6 ng/mL vs. 52.1 ± 17.3 ng/mL, p = 0.04) and in those with seizure duration >5 minutes (p = 0.05). This suggests a possible dose–response relationship, where greater iron deficiency is linked with more severe seizure presentations. Similar associations between iron status and seizure complexity have been reported by Hartfield et al. [12] and Pisacane et al. [13].

Interestingly, while hemoglobin levels were also lower in cases than controls (p = 0.04), other hematological indices (MCV, hematocrit) and inflammatory marker (CRP) did not differ significantly. This indicates that ferritin, rather than general anemia, may have a more direct association with febrile seizures. Since ferritin is an acute-phase reactant, both groups’ febrile state could elevate levels to some extent; yet, the marked difference between cases and controls supports a genuine underlying iron deficiency in the seizure group.

Contradictory results in the literature do exist. For example, Kobrinsky et al. [11] found no association between iron status and febrile seizures, possibly due to differences in population characteristics, nutritional status, or timing of ferritin measurement relative to fever onset.

Limitations of our study include the relatively small sample size and lack of dietary iron assessment. Additionally, as ferritin is influenced by inflammation, even with CRP measurement, some confounding cannot be excluded.

Clinical implications: Early detection and correction of iron deficiency in at-risk children may reduce febrile seizure incidence and severity. Further multicenter studies with larger cohorts and longitudinal follow-up are recommended to clarify causality and assess preventive strategies.

CONCLUSION
This study demonstrates a significant association between lower serum ferritin levels and the occurrence of febrile seizures in children aged 6 months to 5 years. Children with febrile seizures had markedly reduced ferritin compared to age- and sex-matched febrile controls, with the lowest levels observed in complex seizures and longer seizure durations. These findings suggest that iron deficiency may lower the seizure threshold and influence seizure severity. Early screening and correction of iron deficiency could be considered as part of preventive strategies in children at risk for febrile seizures.

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