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This prospective case-control study investigates whether serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), an established biomarker of reactive oxygen species-mediated DNA oxidation, is elevated in children with febrile seizures compared with healthy children, and whether it differs between simple and complex febrile seizure subtypes. Children presenting with a febrile seizure and age-matched healthy controls have serum 8-OHdG measured within 24 hours of seizure onset, alongside routine inflammatory markers (white-cell count, C-reactive protein) and haemoglobin. The primary aim is to determine whether acute oxidative DNA damage is detectable after febrile seizures and whether 8-OHdG levels distinguish simple from complex subtypes. The study is exploratory and hypothesis-generating; it is not designed to establish 8-OHdG as a clinically applicable diagnostic biomarker.
Febrile seizures are the most common convulsive events of early childhood. Oxidative stress contributes to seizure-induced neuronal injury, but clinical data on oxidative DNA damage across febrile seizure subtypes are limited. This single-centre, prospective case-control study was conducted at the paediatric emergency department of Kayseri City Training and Research Hospital between September and December 2021.
Participants were allocated to three groups: children with a simple febrile seizure, children with a complex febrile seizure, and age- and sex-matched healthy controls. After enrolment, a single venous blood sample was obtained from each child within 24 hours of seizure onset (or at presentation for controls). Serum was separated and stored at -80 °C until analysis.
Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) was quantified by a commercial enzyme-linked immunosorbent assay (ELISA), with all samples measured in duplicate. Routine laboratory parameters-white-cell count, haemoglobin, and C-reactive protein-and body temperature were recorded concurrently.
Serum 8-OHdG concentrations were compared among the three groups, and the ability of 8-OHdG to discriminate febrile seizure subtypes was explored. Pre-specified subgroup analyses examined complex febrile seizure patients with versus without febrile status epilepticus, and the relationship between 8-OHdG and inflammatory markers. The analysis was framed as exploratory; the study was not powered to validate 8-OHdG as a diagnostic test.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 Health Controls | Healthy controls (afebrile) n:57 Serum 8-OHdG measurement |
| |
| Group 2 SFC | Simple febrile seizure (SFC) n:50 Serum 8-OHdG measurement |
| |
| Group 3 CFC | Complex febrile seizure (CFC) n:49 Serum 8-OHdG measurement |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Group 1 Health Controls | Diagnostic Test | Single venous blood sample obtained from each participant; serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by enzyme-linked immunosorbent assay (ELISA) within 24 hours of seizure onset. This was an observational measurement only; no therapeutic intervention was administered. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary Outcome Measure | Title: Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration Description: Serum 8-OHdG concentration (ng/mL), quantified by ELISA, compared among children with simple febrile seizure, complex febrile seizure, and healthy controls, to determine whether acute oxidative DNA damage differs across these groups. Time Frame: Within 24 hours of seizure onset (single measurement) Unit of Measure: ng/mL | Time Frame: Within 24 hours of seizure onset (single measurement) |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary Outcome Measures |
|
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Inclusion Criteria:
4) Serum sample obtainable within 24 hours of seizure onset (seizure groups) Written informed consent provided by a parent or legal guardian
Exclusion Criteria:
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Children aged 6 to 72 months presenting to the paediatric emergency department of Kayseri City Training and Research Hospital (Kayseri, Türkiye). Three groups: simple febrile seizure, complex febrile seizure, and age- and sex-matched healthy controls. Participants were enrolled prospectively by convenience sampling from consecutive eligible admissions.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kayseri City Hospital | Kayseri | 38090 | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39395948 | Result | Wang Q, Sun W, Zhao J, Tong L, Li B. Development and validation of a nomogram for the estimation of the prognosis of patients presenting with a febrile seizure. BMC Pediatr. 2024 Oct 12;24(1):655. doi: 10.1186/s12887-024-05132-z. | |
| 36745963 | Result | Poorshiri B, Barzegar M, Afghan M, Shiva S, Shahabi P, Golchinfar Z, Yousefi Nodeh HR, Raeisi S. The effects of ketogenic diet on beta-hydroxybutyrate, arachidonic acid, and oxidative stress in pediatric epilepsy. Epilepsy Behav. 2023 Mar;140:109106. doi: 10.1016/j.yebeh.2023.109106. Epub 2023 Feb 4. |
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De-identified individual participant data underlying the published results (serum 8-OHdG concentrations, demographic and clinical variables, and laboratory parameters) are available from the corresponding author on reasonable request. Data will be shared with qualified researchers whose proposed use has been approved and for purposes consistent with the original ethics approval; a data-use agreement may be required.
Data will become available after publication of the main results and will remain accessible for 5 years thereafter, upon reasonable request to the corresponding author.
Qualified researchers may request access by contacting the corresponding author. Requests will be evaluated for scientific merit and consistency with the original ethics approval, and a data-use agreement may be required before de-identified data are shared.
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| ID | Term |
|---|---|
| D003294 | Seizures, Febrile |
| ID | Term |
|---|---|
| D012640 | Seizures |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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|
| Group 2 SFC | Diagnostic Test | Single venous blood sample obtained from each participant; serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by enzyme-linked immunosorbent assay (ELISA) within 24 hours of seizure onset. This was an observational measurement only; no therapeutic intervention was administered. |
|
| Group 3 CFC | Diagnostic Test | Single venous blood sample obtained from each participant; serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by ELISA within 24 hours of seizure onset. The same measurement was performed in all three groups (healthy controls, simple febrile seizure, and complex febrile seizure). This was an observational measurement only; no therapeutic intervention was administered. |
|
| Within 24 hours of seizure onset |
| 37767398 | Result | Fuchs M, Viel C, Lehto A, Lau H, Klein J. Oxidative stress in rat brain during experimental status epilepticus: effect of antioxidants. Front Pharmacol. 2023 Sep 12;14:1233184. doi: 10.3389/fphar.2023.1233184. eCollection 2023. |
| 38606600 | Result | Lewis DV, Voyvodic J, Shinnar S, Chan S, Bello JA, Moshe SL, Nordli DR Jr, Frank LM, Pellock JM, Hesdorffer DC, Xu Y, Shinnar RC, Seinfeld S, Epstein LG, Masur D, Gallentine W, Weiss E, Deng X, Sun S; FEBSTAT Study Team. Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study. Epilepsia. 2024 Jun;65(6):1568-1580. doi: 10.1111/epi.17979. Epub 2024 Apr 12. |
| 17509462 | Result | Akarsu S, Yilmaz S, Ozan S, Kurt A, Benzer F, Gurgoze MK. Effects of febrile and afebrile seizures on oxidant state in children. Pediatr Neurol. 2007 May;36(5):307-11. doi: 10.1016/j.pediatrneurol.2007.01.010. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |