Hyponatremia and Recurrent Febrile Seizures During Febrile Episodes: A Meta-Analysis

Several studies have investigated the potential effects of hyponatremia on recurrent febrile seizures (RFS) during febrile illness. Because findings were inconsistent across studies, we aimed to evaluate the serum sodium levels in febrile seizures (FS) of children with or without RFS during the same episode. We conducted electronic searches in three databases (PubMed, EMBASE, Cochrane Library) and one scholarly search engine (Google Scholar) up to June 2021 for studies on FS. Screening was done based on the titles and abstracts of primary studies. Then, eligibility was reviewed based on the abstracts. Finally, in order to match the inclusion and exclusion criteria, full-text articles were evaluated by two authors and inconsistencies were discussed. Data extraction was carried out by two independent authors. The extracted variables were author's name, article title, journal name, year of publication, study location, study design, sample size, and mean and standard deviation of blood Na concentration in FS. We performed a risk of bias assessment of included studies using the Newcastle-Ottawa Scale (NOS). The effect size was calculated using the standardized mean difference (SMD), and random-effects models were used for the analysis. A total of 12 articles were included with a single outlier. This analysis suggested that serum sodium level was lower in patients with RFS during the same febrile episode than in those with single FS, with SMD of -0.70, (n=1784; 95% CI: -1.03, -0.36; Z=-4.10, p<0.01; I(2) 86.67%, p<0.01). In the sensitivity analysis, no significant change was observed in pooled SMD. The optimal cutoff value of serum sodium level was 134.72 mmol/L with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.61, 1.00), with sensitivity of 80.0% and specificity of 70.0%. This result indicated a significant association between hyponatremia and RFS during the same febrile episode. Decreased serum sodium levels may be involved in seizure recurrence and may play a role in FS pathogenesis.