Association of Hypocalcemia and Hypomagnesemia with Febrile Seizures

Febrile seizures (FS) are a common neurological event in children, typically occurring between the ages of six months and five years. These seizures are triggered by a rise in body temperature due to fever, often caused by an underlying infection.[1] While the exact cause of febrile seizures remains unclear, several factors have been suggested to contribute, including genetic predisposition, immune responses, and disturbances in electrolyte balance.[2] Among these, abnormalities in serum electrolytes, particularly hypocalcemia and hypomagnesemia, have been frequently associated with febrile seizures, though the exact mechanism linking these deficiencies to seizures is still under investigation. In this context, this study aims to explore the relationship between hypocalcemia, hypomagnesemia, and febrile seizures in children, specifically focusing on their prevalence and potential role in triggering seizures.

Electrolyte imbalances, including disturbances in calcium and magnesium levels, are known to affect neural function, potentially lowering the threshold for seizures. Hypocalcemia, characterized by low calcium levels in the blood, has been documented as a potential cause of seizures, including febrile seizures, due to its effects on nerve cell excitability.[3] In a study, it was found that infants who experienced seizures due to hypocalcemia were also likely to have concomitant low magnesium levels, which could further exacerbate the neurological disturbances.[4] These findings highlight the importance of monitoring both calcium and magnesium levels in children presenting with febrile seizures, particularly in settings where electrolyte imbalances are common.

Magnesium, a vital cofactor in many enzymatic processes, plays a crucial role in maintaining neuronal stability. Studies have shown that hypomagnesemia, or low magnesium levels, can lead to neuronal hyperexcitability, a condition that increases the likelihood of seizure activity.[5] A study conducted a study that demonstrated a significant correlation between low serum magnesium levels and febrile seizures in children. Their research found that children with FS had significantly lower magnesium levels compared to those with fever but no seizures, indicating that magnesium deficiency could be a contributing factor to the development of seizures in febrile children.[6]

Furthermore, the relationship between hypocalcemia, hypomagnesemia, and febrile seizures is not merely coincidental but may reflect a more complex pathophysiological process.[7] For instance, hypocalcemia is often associated with secondary magnesium deficiency, as both electrolytes play interconnected roles in maintaining proper cellular function.[3] This interaction suggests that when one electrolyte level drops, the other may also be affected, increasing the risk of seizure activity. These findings are consistent with earlier studies that reported a higher incidence of seizures in children with combined deficiencies in calcium and magnesium.[8] This underscores the need for comprehensive electrolyte testing in children who present with febrile seizures.

In addition to electrolyte imbalances, genetic factors may also contribute to the occurrence of hypocalcemia and hypomagnesemia. Disorders such as familial hypomagnesemia with secondary hypocalcemia (FHSH) are rare genetic conditions that present with both low calcium and magnesium levels, often leading to refractory seizures in affected children.[8] Such conditions highlight the importance of genetic screening in children with recurrent febrile seizures, particularly in cases where standard treatment for electrolyte imbalances does not lead to resolution of symptoms.

In Pakistan, where the prevalence of febrile seizures is relatively high, electrolyte disturbances are a significant concern. A study conducted in Pakistan showed that iron deficiency anemia, another common nutritional deficiency, was strongly associated with febrile seizures.[9] Though this study focused on iron deficiency, it points to the broader issue of micronutrient deficiencies in the region, including calcium and magnesium, which are less frequently studied but may contribute to the pathophysiology of febrile seizures.[10] This adds weight to the need for further research on the role of electrolyte imbalances, particularly hypocalcemia and hypomagnesemia, in the development of febrile seizures in children in Pakistan.

The rationale for this study is based on the growing body of evidence suggesting that disturbances in calcium and magnesium homeostasis could increase the risk of febrile seizures in children. Despite some studies suggesting a link, there is still a lack of consensus on the exact relationship between these deficiencies and the occurrence of seizures. The objective of this study is, therefore, to determine the association of hypocalcemia and hypomagnesemia with febrile seizures. This research aims to provide a clearer understanding of how these electrolyte imbalances may act as risk factors for febrile seizures, ultimately contributing to the development of targeted prevention and treatment strategies in pediatric care. The objective of this study is to determine the association of hypocalcemia and hypomagnesemia with febrile seizures.

Overview and Patient Count

A total of 200 children were included in the study, divided equally into two groups: the case group consisting of 100 children with febrile seizures and the control group consisting of 100 children with fever but no seizures. The demographic characteristics of the participants, including age, gender, and other relevant variables, were recorded and are summarised in the following sections.

 Demographic Characteristics

The age of the participants ranged from 6 months to 60 months, with a mean age of 28.45±11.72 months. The gender distribution was fairly balanced, with 51% (n = 102) of the participants being male (51.0%) and 49% (n = 98) being female (49.0%). The demographic characteristics are presented in Table 1 below.

 Table 1: Demographic Characteristics of Participants

 Electrolyte Levels and Prevalence of Imbalances

The mean serum calcium level in the entire study population was 8.67±0.86 mg/dL. Notably, 36% (n = 72) of the children had hypocalcemia, defined as a serum calcium level of less than 8.5 mg/dL. In the case group, 41% (n = 41) had hypocalcemia, while 31% (n = 31) of the control group had hypocalcemia. This difference was not statistically significant (p = 0.775).

 The mean serum magnesium level was 2.02±0.26 mg/dL. In total, 27% (n = 54) of the children exhibited hypomagnesemia (serum magnesium <1.7 mg/dL), with 30% (n = 30) in the case group and 24% (n = 24) in the control group. Again, the difference was not statistically significant (p = 0.596).

 Table 2: Prevalence of Electrolyte Imbalances

 Association Between Electrolyte Imbalances and Febrile Seizures

The association between hypocalcemia and febrile seizures was analysed using a chi-square test. The results revealed that there was no significant association between hypocalcemia and febrile seizures (p = 0.775). Similarly, the analysis of the relationship between hypomagnesemia and febrile seizures also showed no statistically significant association (p = 0.596). These findings suggest that although both hypocalcemia and hypomagnesemia are common in children with febrile seizures, they do not significantly influence the occurrence of seizures in this population.

 Comorbidities and Other Confounding Variables

The study also considered potential confounding variables, such as underlying infections and comorbidities, which may have affected the relationship between electrolyte imbalances and febrile seizures. Among the children with febrile seizures, 23% (n = 23) had a history of respiratory infections, while 17% (n = 17) had a family history of seizures. Among the children in the control group, 18% (n = 18) had respiratory infections, and 10% (n = 10) had a family history of seizures. However, these factors were not found to significantly influence the occurrence of seizures in either group (p > 0.05).

Table 3: Comorbidities and Confounding Variables

 Chi-Square Test Results

Chi-square tests were performed to evaluate the association between hypocalcemia, hypomagnesemia, and febrile seizures. The p-values obtained were 0.775 for hypocalcemia and 0.596 for hypomagnesemia, indicating no significant association. These results are summarised in Table 4.

 Table 4: Chi-Square Test Results

 The following figures visualise the distribution of electrolyte imbalances and their relationship with febrile seizures. The charts support the statistical findings presented above, showing that there is no significant difference in the prevalence of hypocalcemia or hypomagnesemia between the case and control groups.

This study aimed to investigate the association of hypocalcemia and hypomagnesemia with febrile seizures in children aged 6 to 60 months. The results showed that while both hypocalcemia and hypomagnesemia were prevalent among children with febrile seizures, the statistical analysis indicated no significant association between these electrolyte imbalances and the occurrence of febrile seizures. The chi-square test for hypocalcemia and seizure recurrence yielded a p-value of 0.775, and for hypomagnesemia and seizure recurrence, the p-value was 0.596. Additionally, other confounding variables, such as a history of seizures and underlying infections, did not significantly impact the results. Despite the observed prevalence of these electrolyte imbalances, the study concluded that they do not significantly contribute to the onset of febrile seizures in the Pakistani population studied.

 The novelty of this study lies in its local context, as it is one of the few studies examining the relationship between electrolyte disturbances, specifically hypocalcemia and hypomagnesemia, and febrile seizures in Pakistani children. While electrolyte imbalances are well-documented in febrile seizures, there has been limited research exploring this relationship in Pakistan. The findings of this study contribute to the understanding of the clinical significance of electrolyte disturbances in febrile seizures within the local context, particularly given the high rates of febrile seizures in children in Pakistan. Furthermore, the study employed a robust methodology and included a substantial sample size, ensuring that the findings are reliable and relevant to clinical practice in the country.

 Globally, many studies have explored the association between hypocalcemia, hypomagnesemia, and febrile seizures. Research from the United States and Europe has consistently shown that electrolyte imbalances, including hypocalcemia and hypomagnesemia, are commonly observed in children with febrile seizures.[12] However, these studies have also reported varying results, with some finding a significant association between low serum calcium and magnesium levels and the occurrence of febrile seizures, while others have not observed any such relationship.[6] The current study's findings align with these international results, as no significant association was observed in the Pakistani cohort.

 In the global context, studies have indicated that electrolyte disturbances, particularly hypocalcemia and hypomagnesemia, can lead to an increased risk of febrile seizures. For example, a study found that hypocalcemia in children with febrile seizures was a contributing factor, particularly in the presence of complex febrile seizures.[3] However, similar studies conducted in Western countries have often shown mixed results, with some indicating a direct correlation and others finding no significant effect.[13].

 In contrast, the findings of this study support the position taken by some European studies, which found no significant relationship between electrolyte imbalances and febrile seizures.[12] This contrast in findings between studies in different geographical locations can be attributed to variations in population characteristics, environmental factors, healthcare access, and clinical practices. In Pakistan, where nutritional deficiencies, including calcium and magnesium, are prevalent, it may be useful for clinicians to consider these factors when managing febrile seizures, even though this study did not find a significant correlation.

 Globally, there have been numerous studies on electrolyte imbalances in febrile seizures, with significant contributions from Europe and the United States. Research found that serum magnesium deficiency was significantly associated with febrile seizures,[6] with children having lower serum magnesium levels being more likely to experience seizures. Similarly, studies in the United States and Europe have reported a link between hypocalcemia and the frequency and severity of febrile seizures.[3],[13] However, these studies primarily focused on different populations with different clinical profiles and healthcare settings.

 On the other hand, studies from low-resource settings, including some countries in Africa, have shown a higher prevalence of hypocalcemia and hypomagnesemia in children with febrile seizures due to nutritional deficiencies, which is a common concern in developing countries.[14] The local literature has reported similar findings, albeit with a focus on other causes such as iron deficiency, which could potentially explain the underlying mechanisms of febrile seizures in Pakistan.

As far as our review of local literature goes, this study is unique in its focus on hypocalcemia and hypomagnesemia in relation to febrile seizures in Pakistani children. While there have been studies in Pakistan examining the prevalence of febrile seizures,[9] no significant research has been conducted specifically exploring the role of electrolyte imbalances like hypocalcemia and hypomagnesemia in febrile seizures. This gap in research is particularly important given the high rates of febrile seizures in children in Pakistan, with studies suggesting that approximately 8% to 10% of children experience febrile seizures, which is notably higher than in Western countries.[15].

 This study offers a valuable contribution to the growing body of literature by providing insights into the role of electrolyte disturbances in febrile seizures in Pakistan. The findings of this research can be useful in guiding future studies and improving clinical management of febrile seizures in children, particularly in under-resourced healthcare settings where electrolyte imbalances may be more prevalent.

 In local Pakistani literature, febrile seizures have been widely reported as a common paediatric condition, with studies indicating that iron deficiency is a common co-morbidity.[9] However, electrolyte disturbances like hypocalcemia and hypomagnesemia have not received as much attention. The findings from this study could prompt future research into the role of calcium and magnesium imbalances in febrile seizures in Pakistan and help clinicians consider these factors in diagnosis and treatment.

 Study Limitations and Future Directions

While this study provides important insights, it has several limitations. First, the study was conducted in a single hospital setting, which limits the generalizability of the findings to other regions or settings within Pakistan. Second, the cross-sectional design of the study means that causal inferences cannot be made regarding the relationship between electrolyte imbalances and febrile seizures. Future longitudinal studies with larger sample sizes and multi-centre data collection would be beneficial in confirming the findings and addressing these limitations.

 Additionally, the study did not account for other potential confounding variables such as diet, environmental factors, and genetic predispositions, all of which could contribute to electrolyte imbalances and febrile seizures. Further research examining these factors in a more comprehensive manner would provide a more nuanced understanding of the underlying mechanisms of febrile seizures in children.

In conclusion, this study aimed to explore the association between hypocalcemia, hypomagnesemia, and febrile seizures in children aged 6 to 60 months in Pakistan. The results revealed that while both hypocalcemia and hypomagnesemia were prevalent among children with febrile seizures, there was no significant association between these electrolyte disturbances and the occurrence of seizures. This finding suggests that while electrolyte imbalances are common in children with febrile seizures, they may not be the primary contributing factors to seizure onset in this population. The study’s results contribute to the existing body of literature on febrile seizures, offering valuable insights in the local Pakistani context. However, given the limitations of a single-centre study and the cross-sectional design, further research through larger, multicenter prospective studies is recommended to confirm these findings and explore other potential contributing factors.