8-OHdG and Oxidative Stress in Febrile Seizures

Serum 8-Hydroxy-2'-Deoxyguanosine (8-OHdG) and Oxidative DNA Damage in Children With Simple and Complex Febrile Seizures: An Exploratory Prospective Case-Control Study

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.

Inclusion Criteria:

1. Age between 6 and 72 months
2. Presentation with a febrile seizure (simple or complex) to the paediatric emergency department, OR healthy age- and sex-matched child (control group) 3) For seizure groups: a seizure occurring in the context of fever, meeting clinical criteria for simple or complex febrile seizure

4) Serum sample obtainable within 24 hours of seizure onset (seizure groups) Written informed consent provided by a parent or legal guardian

Exclusion Criteria:

1. Central nervous system (CNS) infection (e.g., meningitis, encephalitis)
2. Known epilepsy or prior afebrile seizures
3. Neurodevelopmental delay
4. Chronic systemic illness
5. Use of antioxidant supplements within the preceding 3 months
6. Incomplete clinical or laboratory data