Febrile seizures are the most common seizure disorder in childhood, affecting approximately 2–5% of children worldwide, with the highest incidence between 6 months and 5 years of age [1]. They are defined as seizures occurring in association with fever in the absence of central nervous system infection, metabolic abnormalities, or previous afebrile seizures [2]. In India, febrile seizures account for a considerable proportion of pediatric emergency admissions and remain a major source of parental anxiety despite their generally favorable prognosis [3]. Although genetic susceptibility, fever, and inflammatory mediators are recognized contributors, nutritional deficiencies have increasingly been investigated as potential risk factors [4]. Iron deficiency anemia (IDA) is the most common micronutrient deficiency among children worldwide and is highly prevalent in low- and middle-income countries, including India [5]. Iron is essential for brain development, myelination, oxygen transport, and the synthesis of neurotransmitters such as dopamine, serotonin, and γ-aminobutyric acid (GABA) [6]. Deficiency of iron may impair neuronal metabolism and lower the seizure threshold during febrile illnesses [7]. Previous studies have reported conflicting findings regarding the association between iron deficiency anemia and febrile seizures, with some demonstrating a significant relationship while others found no association [8–10]. Considering the high prevalence of iron deficiency anemia and the inconsistent evidence regarding its role in febrile seizures, further evaluation is warranted. Identification of iron deficiency as a modifiable risk factor could facilitate early diagnosis and treatment, thereby reducing the burden of febrile seizures. Therefore, the present study was undertaken to evaluate the association between iron deficiency anemia and first febrile seizure in children by comparing hematological and biochemical indicators of iron status with those of febrile children without seizures.

Study design and setting A prospective hospital-based case-control study was conducted in the Department of Pediatrics of a tertiary care teaching hospital. Study participants A total of 100 children aged 6 months to 6 years were included in the study. Fifty children presenting with first febrile seizure constituted the case group, while fifty age- and sex-matched children with febrile illness without seizures served as the control group. Inclusion criteria Cases • Children aged 6 months to 6 years. • First episode of febrile seizure. • Fever (≥38°C) without evidence of central nervous system infection. Controls • Children aged 6 months to 6 years. • Febrile illness without seizures. • Age- and sex-matched with cases. Exclusion criteria Children with any of the following were excluded: • Previous febrile seizures. • Epilepsy or afebrile seizures. • Meningitis or encephalitis. • Developmental delay or neurological disorders. • Chronic systemic illnesses. • Hematological disorders other than iron deficiency anemia. • History of iron therapy during the previous three months. Data collection A detailed clinical history and physical examination were performed for all participants. Information regarding age, sex, duration of seizure, type of seizure, cause of fever, and family history of febrile seizures was recorded. Assessment of nutritional status Nutritional status was assessed according to the Indian Academy of Pediatrics (IAP) classification based on weight-for-age. Children were categorized as: • Normal nutrition • Grade I protein energy malnutrition (PEM) • Grade II PEM • Grade III PEM • Grade IV PEM Laboratory investigations Venous blood samples were collected before initiation of treatment. The following investigations were performed: • Hemoglobin (Hb) • Mean corpuscular volume (MCV) • Mean corpuscular hemoglobin (MCH) • Serum ferritin • Serum iron • Total iron-binding capacity (TIBC) • Serum transferrin Iron deficiency anemia was diagnosed based on low hemoglobin concentration with supportive biochemical evidence of iron deficiency, including low serum ferritin and serum iron, and elevated TIBC. Statistical analysis Data were analyzed using the Statistical Package for the Social Sciences (SPSS). Continuous variables were expressed as mean ± standard deviation and compared using Student's t-test. Categorical variables were expressed as frequency and percentage and analyzed using the Chi-square test. A P value <0.05 was considered statistically significant. Ethical considerations The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from the parents or legal guardians of all participating children before enrollment.

A total of 100 children were enrolled in the study, comprising 50 children with first febrile seizure (cases) and 50 children with febrile illness without seizures (controls). The demographic characteristics of the two groups were comparable. The results focused on seizure characteristics, etiology of fever, nutritional status, hematological parameters, iron profile, and final diagnosis. Table 1. Average duration of seizures among the study participants Duration Cases (n=50) Controls (n=50) P value <5 min 39 (78.0%) 0 <0.001 5–10 min 11 (22.0%) 0 <0.001 >10 min 0 2 (4.0%) 0.495 The majority of seizures (78%) lasted for less than five minutes, while the remaining 22% lasted between five and ten minutes. None of the children experienced seizures lasting more than ten minutes. These findings indicate that most episodes were short-lasting and consistent with simple febrile seizures. Table 2. Type of seizure observed in the study population Seizure Type Cases (n=50) Controls (n=50) P value Generalized tonic-clonic seizure 49 (98.0%) 2 (4.0%) <0.001 Focal seizure 1 (2.0%) 0 1.000 Tonic 0 0 NS Clonic 0 0 NS Complex partial 0 0 NS Atonic 0 0 NS Febrile status epilepticus 0 0 NS Generalized tonic-clonic seizure was the predominant seizure type, accounting for 98% of cases. Only one child (2%) presented with a focal seizure. None of the children had tonic, clonic, atonic, complex partial seizures, or febrile status epilepticus. Table 3. Etiology of fever among cases and controls Etiology Cases (n=50) Controls (n=50) P value Upper respiratory tract infection 41 (82.0%) 42 (84.0%) 0.338 Acute gastroenteritis 9 (18.0%) 8 (16.0%) 0.790 Post-vaccination fever 0 0 NS Upper respiratory tract infection was the most common cause of fever in both groups, accounting for more than four-fifths of patients. Acute gastroenteritis was the second most common etiology. No febrile seizure occurred following routine immunization. There was no statistically significant difference in the etiology of fever between cases and controls. Table 4. Nutritional status according to IAP classification Nutritional Status Cases (n=50) Controls (n=50) P value No PEM 37 (74.0%) 20 (40.0%) 0.001 Grade I PEM 9 (18.0%) 6 (12.0%) 0.401 Grade II PEM 5 (10.0%) 14 (28.0%) 0.022 Grade III PEM 0 2 (4.0%) 0.495 Grade IV PEM 0 0 NS Most children in the febrile seizure group had normal nutritional status (74%). Grade II protein-energy malnutrition was significantly more common among controls than cases. Overall, nutritional status did not appear to explain the observed differences in iron parameters between the two groups. Table 5. Comparison of hematological parameters Parameter Cases (Mean ± SD) Controls (Mean ± SD) P value Hemoglobin (g/dL) 8.92 ± 1.18 9.55 ± 0.96 <0.001 MCV (fL) 67.03 ± 15.63 84.12 ± 13.78 <0.001 MCH (pg) 30.60 ± 13.81 37.32 ± 9.57 0.006 Children with febrile seizures had significantly lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin compared with febrile controls. These findings indicate a higher prevalence of microcytic hypochromic anemia among children with febrile seizures. Table 6. Comparison of iron profile between cases and controls Parameter Cases (Mean ± SD) Controls (Mean ± SD) P value Plasma ferritin (µg/L) 45.00 ± 64.09 54.22 ± 24.02 <0.03 Serum iron (µg/dL) 77.65 ± 44.71 95.20 ± 38.08 0.037 TIBC (µg/dL) 434.86 ± 125.18 354.14 ± 103.10 0.001 Serum transferrin (mg/dL) 248.64 ± 64.43 290.42 ± 49.62 <0.001 Children with first febrile seizure demonstrated significantly lower plasma ferritin and serum iron concentrations compared with controls. Total iron-binding capacity was significantly elevated among cases, indicating depleted iron stores. Serum transferrin levels also differed significantly between the two groups. Overall, the biochemical profile supported the presence of iron deficiency among children with febrile seizures. Table 7. Final diagnosis among study participants Diagnosis Cases (n=50) Controls (n=50) P value Iron deficiency anemia with febrile illness/febrile seizure 29 (58.0%) 9 (18.0%) <0.003 Febrile seizure without iron deficiency anemia 21 (42.0%) 0 <0.001 Other febrile illnesses 0 41 (82.0%) <0.001 Iron deficiency anemia was diagnosed in 58% of children with first febrile seizure compared with only 18% of children with febrile illness without seizures. This difference was statistically significant (P < 0.003), indicating a strong association between iron deficiency anemia and the occurrence of first febrile seizure.

The present study evaluated the association between iron deficiency anemia and first febrile seizure in children. Most seizures lasted less than five minutes, indicating that the majority were simple febrile seizures. Similar observations have been reported in previous studies, which showed that most febrile seizures are generalized, short-lasting, and self-limiting [11,12]. Generalized tonic-clonic seizure was the predominant seizure type in the present study. This finding is comparable with earlier reports, where generalized seizures constituted the majority of febrile seizure episodes [11,13]. The predominance of generalized seizures supports the typical clinical profile of simple febrile seizures. Upper respiratory tract infection was the most common cause of fever in both cases and controls. Viral respiratory infections are recognized as common precipitants of febrile seizures because they are frequently associated with rapid elevation of body temperature and increased production of inflammatory mediators [14,15]. The similar distribution of febrile illnesses in both groups suggests that factors other than the type of infection, particularly iron status, may contribute to seizure susceptibility. Nutritional assessment showed that most children had normal nutritional status, while a smaller proportion had varying grades of PEM. Similar findings have been reported in previous pediatric studies, which observed that febrile seizures can occur even in children with apparently normal nutritional status [16]. Therefore, the association observed in the present study is unlikely to be explained solely by generalized malnutrition. Children with febrile seizures had significantly lower hemoglobin, MCV, and MCH values than controls, indicating the presence of microcytic hypochromic anemia. Similar reductions in hematological indices have been reported by Daoud et al., Hartfield et al., and Vaswani et al., who demonstrated a higher prevalence of iron deficiency among children with febrile seizures [17–19]. The biochemical parameters of iron status further supported these findings. Serum ferritin and serum iron were significantly lower, whereas TIBC was significantly higher in children with febrile seizures. Low ferritin reflects depleted body iron stores, while elevated TIBC is a characteristic feature of iron deficiency. Comparable results have been documented in previous case-control studies evaluating iron status in febrile seizure patients [17–20]. In the present study, 58% of children with first febrile seizure had iron deficiency anemia compared with 18% of febrile controls, demonstrating a statistically significant association between iron deficiency anemia and febrile seizures. Similar findings have been reported in several studies, which concluded that iron deficiency may act as an independent risk factor for febrile seizures [8,9,18,19]. Iron is essential for neurotransmitter synthesis, myelination, and cerebral oxygen transport; therefore, deficiency of iron may lower the seizure threshold during febrile illnesses [6,7,20]. Overall, the findings of the present study indicate that iron deficiency anemia is significantly associated with first febrile seizure and support the role of iron deficiency as a potentially modifiable risk factor in children presenting with febrile seizures.

The present case-control study demonstrated a significant association between iron deficiency anemia and first febrile seizure in children aged 6 months to 6 years. Children with febrile seizures had significantly lower hemoglobin, MCV, MCH, serum ferritin, and serum iron levels, while TIBC was significantly higher compared with febrile controls. Iron deficiency anemia was present in more than half of the children with first febrile seizure, suggesting that depleted iron stores may increase susceptibility to seizures during febrile illnesses. Routine evaluation of iron status in children presenting with a first febrile seizure may facilitate early diagnosis and treatment of iron deficiency and may help reduce the occurrence of febrile seizures in susceptible children.

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