Abstract / Summary
Differentiating simple febrile seizures (SFS) from complex febrile seizures (CFS) at initial presentation is critical for guiding clinical management, yet current practice relies on seizure histories that are often unreliable. This study aimed to develop and internally validate a nomogram incorporating IL-1β, IL-6, and vitamin D as an adjunctive tool for distinguishing CFS from SFS. This retrospective single-center study enrolled 219 children with febrile seizures (118 SFS, 101 CFS) between January 2023 and December 2024. Serum levels of IL-1β, IL-6, 25-hydroxyvitamin D, and other inflammatory biomarkers were measured within 30 min of admission. Multivariable logistic regression was applied to identify independent predictors. A nomogram was constructed, and model performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), calibration plots, and decision curve analysis (DCA) with 1000 bootstrap resampling iterations. Subgroup analysis by age (≤ 3 years vs. >3 years) and continuous interaction analysis were performed to evaluate the model’s consistency across age strata and to test for effect modification. Multivariable analysis identified IL-1β as independently associated with higher odds of CFS (adjusted OR = 1.085, 95% CI: 1.042–1.130, p < 0.001), whereas IL-6 (adjusted OR = 0.919, 95% CI: 0.890–0.948, p < 0.001) and 25-hydroxyvitamin D (adjusted OR = 0.889, 95% CI: 0.847–0.933, p < 0.001) were independently associated with lower odds of CFS. The combined model demonstrated excellent discriminative ability with an AUC of 0.860 (95% CI: 0.813–0.907), significantly outperforming each individual biomarker (all p < 0.05). At the optimal cutoff of 61.3%, sensitivity was 84.2% and specificity was 77.1%. Calibration was satisfactory (Hosmer–Lemeshow χ ² = 13.848, df = 8, p = 0.086), and DCA confirmed a positive net clinical benefit across clinically relevant threshold probabilities. Age-stratified and continuous interaction analyses demonstrated consistent model performance across age strata (AUC: 0.860 and 0.865 for ≤ 3 vs. >3 years subgroups, respectively; all p for interaction > 0.05). The nomogram integrating IL-1β, IL-6, and vitamin D demonstrated strong discriminative ability and clinical net benefit for distinguishing CFS from SFS. Its performance remained consistent across age subgroups and CFS subtypes, supporting its potential use as an adjunctive risk-stratification tool in centers where rapid multiplex cytokine testing is available. Not applicable.