Scatter dot plots of serum copeptin and prolactin values in the three study groups.

<p>Medians and interquartile ranges are also presented. Between-group comparisons were performed with Mann-Whitney U test. * Serum copeptin values in 4 cases (range 208–306 pmol/L) are outside the copeptin-axis limits of the graph. FS: febrile seizures; ES: epileptic seizures</p

Copeptin as a Serum Biomarker of Febrile Seizures

<div><p>Background and Objectives</p><p>Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion.</p><p>Methods</p><p>This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. Clinical Trial Registration: NCT01884766.</p><p>Results</p><p>Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; <i>p</i> <0.001), with no differences between febrile and epileptic seizures (21.4 pmol/L [16.1-46.6]; p = 0.728). In a multivariable regression model, seizures were the major determinant of serum copeptin (<i>beta</i> 0.509; <i>p</i> <0.001), independently of clinical and baseline laboratory indices. The area under the receiver operating curve for copeptin was 0.824 (95% CI 0.753-0.881), significantly higher compared to prolactin (0.667 [0.585-0.742]; <i>p</i> <0.001). The diagnostic accuracy of copeptin increased with decreasing time elapsed since the convulsive event (at 120 min: 0.879 [0.806-0.932] and at <60 min: 0.975 [0.913-0.997]).</p><p>Conclusions</p><p>Circulating copeptin has high diagnostic accuracy in febrile seizures and may be a useful adjunct for accurately diagnosing postictal states in the emergency setting.</p></div

Diagnostic performance of selected copeptin cut-off values.

<p>* optimal criterion according to the sum of sensitivity and specificity.</p><p>Diagnostic performance of selected copeptin cut-off values.</p

Copeptin dependencies in febrile children with or without seizures.

<p>Unadjusted and adjusted effect of each factor was calculated by simple and multivariable linear regression analysis using serum copeptin values (after logarithmic transformation) as the dependent variable. Only factors with statistically significant unadjusted effects were considered for the adjusted models.</p><p>* children with epileptic seizures are excluded.</p><p>Copeptin dependencies in febrile children with or without seizures.</p

Characteristics of study groups.

<p>Data are presented as median (IQR) unless stated otherwise.</p><p>*Blood analysis results at presentation.</p><p>^†p <0.05,</p><p>^‡p <0.01, and</p><p>^§p <0.001 for comparisons between febrile seizures and controls.</p><p>^¶p <0.05,</p><p>^**p <0.01, and</p><p>^††p <0.001 for comparisons between febrile and epileptic seizures.</p><p>Between-group comparisons were performed with Mann-Whitney U, chi square or Fisher's exact test as appropriate. ED: emergency department; URTI: upper respiratory tract infection; LRTI: lower respiratory tract infection; UTI: urinary tract infection.</p><p>Characteristics of study groups.</p

Receiver operating characteristic curves of serum copeptin and prolactin.

<p>(A) In controls (n = 69) and in children with febrile seizures irrespectively to the time of presentation (n = 83); (B) In controls (n = 69) and in children with febrile seizures presented <120 minutes since the event (n = 53); (C) In controls (n = 69) and in children with febrile seizures presented <60 minutes since the event (n = 14).</p