Risk factors description of febrile seizures among pediatric patients: a retrospective study at King Abdulaziz University Hospital in Jeddah, Saudi Arabia

Introduction

Background

Febrile seizures (FS) are the most common childhood seizure type, occurring in 2% to 5% in children between 6 months to 5 years old (1,2). FS are seizures associated with fever (mostly more than 38 ℃) in the absence of central nervous system (CNS) infection, metabolic imbalance, and history of afebrile seizure (3). The exact pathophysiology of FS is unknown therefore multiple risk factors have been found including several genetic mutations (history of first or second-degree relative with a history of FS), High-grade fever of more than 40 ℃, recurrent episodes of fever (>4 per year), viral infection, and recent Immunization (1,4-6). Many studies have reported genetic and environmental risk factors for FS in children (6,7). Alterations in genes coding for gamma amino butyric acid (GABA) receptor and sodium voltage-gated channel alpha subunit (SCN1A) are known to be associated with FS (7,8). Moreover, a study identified another genetic cause including a duplication in the 17q12 chromosome (8). Other reported risk factors for the first FS are maternal factors like smoking, alcoholism, stress, premature birth, prolonged neonatal intensive care unit (NICU) stay, neonatal discharge after 28 days, parental perception of slow development, daycare attendance, FS in first-degree relatives, afebrile seizures in first-degree relatives, micro-nutrient deficiencies like iron and zinc deficiency (9-12). A case-control study that included patients with FS and a control group highlighted that the risk factors for the development of the first episode of FS are male gender, low serum calcium, sodium, blood sugar, and microcytic hypochromic anemia (13). Furthermore, seizure risk increases in those patients with high leukocyte counts, and high neutrophil counts (14). They can also vary significantly by region and ethnicity. Genetic predispositions differ between ethnic groups, affecting susceptibility to FS (15). Environmental factors such as climate, healthcare access, and prevalent infections all contribute to the incidence of FS (16). Furthermore, cultural practices influence healthcare-seeking behavior and management strategies (17). Socioeconomic disparities influence nutrition, healthcare access, and vaccination rates, all of which have an impact on FS risk (18). In some areas, higher rates of consanguinity can exacerbate genetic predispositions (19). Understanding these differences is critical for developing effective prevention and management strategies for diverse populations.

Rationale and knowledge gap

The limited research on FS conducted in Saudi Arabia presents a significant gap in understanding the prevalence and risk factors associated with this common pediatric condition within the local population. The scarcity of studies in Saudi Arabia addressing FS risk factors leaves healthcare providers and policymakers with inadequate data to develop targeted strategies for early identification, management, and prevention of FS in the local pediatric population.

Objective

Therefore, this retrospective study aimed to describe the risk factors that can predispose children to FS in King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. We present this article in accordance with the STROBE reporting checklist (available at https://pm.amegroups.com/article/view/10.21037/pm-24-35/rc).

Methods

Study design

This study employed a retrospective research design to investigate the factors associated with FS among pediatric patients at KAUH in Jeddah, Saudi Arabia. In our tertiary care center, the protocol for managing FS typically includes initial assessment based on the mode of entry of the patient (i.e., emergency department or outpatient clinics), clinical description to determine the nature of the seizure event, laboratory tests if indicated and including blood culture if a bacterial infection is suspected, lumbar puncture to be considered especially if signs of meningitis are presented, electroencephalogram (EEG) can be considered only with atypical features or recurrent complex seizures otherwise is not routinely recommended for simple FS, and neuroimaging only in cases of complex seizures or abnormal neurological findings while in simple FS it is not routinely conducted. Given the tertiary nature of our center and the amount of referral of complex cases, many tests are included in our patients in contrast to routine practice.

Inclusion criteria

The study included male and female pediatric patients aged 6 months to 6 years who were diagnosed with FS. FS were defined as convulsions occurring in association with fever in the absence of CNS infection at presentation (Figure 1), complex FS due to bacterial meningitis were included (as clinically approach always the bacterial meningitis is one of the most common differential diagnosis should be excluded or manage it as soon as possible).

Figure 1 Diagram chart of the inclusion and exclusion process.

Exclusion criteria

Patients with a history of non-FS, those known cases of epilepsy, or not documented fever at the presentation.

Data collection

Data for the study were retrieved on December 2023 from the KAUH data system [Vida-Cloud Solutions, 2023, version 1]. A retrospective review of medical records was conducted to gather relevant information on pediatric patients who met the inclusion criteria using the International Classification of Diseases (ICD)-10 codes related to FS. The timeframe included cases visiting from January 2013 to 2022. Data collected included demographic information, such as age and gender, as well as potential risk factors associated with FS.

Data analysis

The recommended sample size was calculated using a non-probability sampling technique to achieve a 95% confidence interval (CI) with a 5% margin of error using Raosoft Sample Size Calculator software. A minimum suggested sample of 200 was proposed and we included a total of 173 patients. IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, NY, USA) was used to analyze data. Descriptive statistics were used to summarize categorical variables, including frequencies, to describe the demographic characteristics of the study population. Continuous variables were described using measures of central tendency (mean) and dispersion [standard deviation (SD)] for normally distributed data. Missing data from the files was obtained by directly contacting the parents or legal guardian of patients. For the analytical statistics, the Chi-square test was utilized to examine the associations between categorical variables and FS. A P value less than 0.05 was considered statistically significant.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics of King Abdulaziz University (No. 266-23) and individual consent for this retrospective analysis was waived.

Results

We included a total cohort of 173 patients. Table 1 presents the patient characteristics and clinical history of the pediatric patients included in the study. The mean age of the patients was 36.17 months (SD =17.98). Among the patients, 58.4% were male and 41.6% were female. The majority of patients (56.6%) experienced their first episode of FS, while 43.4% had a previous history of FS. Among those who had previous seizures, the mean age at the first episode was 16.57 months (SD =11.61). The duration of seizures was more than 5 minutes in 68.8% of cases, while 31.2% had seizures lasting less than 5 minutes. Generalized seizures were observed in 89.6% of cases, while 10.4% had focal seizures. Recurrence within 24 hours was reported in 19.1% of cases, and febrile status epilepticus was present in 71.1% of cases. Developmental delay was reported in 56.6% of cases, with the majority (93.9%) affecting all domains. Most patients (84.4%) were up to date with their vaccinations, while 15.6% had delayed vaccinations. Table 2 provides information on environmental and family factors. Among the patients, 30.6% attended daycare, while the majority (85.0%) were born full term. A small percentage (16.8%) had a neonatal nursery stay of more than 30 days. Consanguinity of parents was reported in 54.3% of cases. Family history of FS was present in 6.9% of cases, with the father (30.0%) and mother (30.0%) being the most commonly affected family members. Family history of epilepsy was reported in 5.2% of cases. Table 3 presents fever characteristics and diagnostic findings. The most common cause of fever among the patients was upper respiratory tract infection (52.6%), followed by bacterial meningitis (6.9%), and gastroenteritis (5.8%). The peak temperature during FS was less than 39 ℃ in 80.3% of cases. Positive meningeal signs were observed in 5.8% of cases. Among the patients who underwent imaging, 55.5% had normal findings, while the remaining patients showed various abnormalities such as brain atrophy (16.2%) and hydrocephalus (9.2%). EEG findings were normal in 90.8% of cases, with a small percentage showing slow background (2.9%) or epileptiform discharge (4.0%). To assess the associations between different variables and FS, various statistical analyses were conducted including seizure type and gender (P=0.45), whether it was the first episode of FS (P=0.92), average duration of seizure (P=0.46), history of recurrence within 24 hours (P=0.78), presence of febrile status epilepticus (P=0.12), developmental delay (P=0.10), vaccination status (P=0.58), daycare attendance (P=0.79), gestation (P=0.11), neonatal nursery stay of more than 30 days (P=0.19), consanguinity of parents (P=0.11), family history of FS (P=0.81), cause of fever (P=0.67), peak temperature (P=0.34), or presence of positive meningeal signs (P=0.27) (Table 4).

Discussion

Key findings

The results of this retrospective study provide important insights into the characteristics and risk factors associated with FS among pediatric patients in Jeddah, Saudi Arabia. FS are a prevalent neurological condition in children (20,21), and it is possible to prevent and control them with more knowledge of the contributing variables. The study revealed that a significant proportion of the patients enrolled in the research encountered FS for the first time. This finding suggests that FS frequently occur as an isolated incident. This discovery aligns with other research indicating that a significant proportion of FS in children are transient in nature and do not exhibit recurrent patterns (21,22). Nevertheless, it is important to acknowledge that a considerable percentage of the participants in this research had a prior medical record of FS, suggesting that recurrent FS may manifest in certain instances. Additionally, generalized seizures were more prevalent than focal seizures among the individuals, according to the study. Focal seizures arise in a particular region of the brain, whereas generalized seizures first affect both hemispheres. This finding is consistent with prior investigations that indicate generalized seizures constitute the prevailing form of FS among younger patients (20,23). Differentiating between focal seizures and generalized seizures is critical, given that the latter could potentially signify an underlying structural anomaly in the brain and so necessitate more examination (24). More than half of the cases documented developmental delay, with the majority of affected individuals exhibiting deficits across all areas of development. This finding underscores the possible correlation between FS and neurodevelopmental consequences (25,26).

Comparison with similar research

Multiple studies have established a correlation between FS and developmental delay or cognitive impairment (27-30). The specific causal association between FS and developmental delay, which requires further exploration, is still unknown. In our cohort, only four individuals were identified with FS attributed to electrolytic disorders, representing a prevalence of 2.3%. The rarity of this occurrence aligns with the general understanding of its infrequency. Given its secondary relevance within the study, detailed elaboration on management strategies in the inclusion criteria was deemed unnecessary. Nevertheless, the management of such cases typically involves initial monitoring and stabilization, followed by laboratory investigations to ascertain any electrolyte imbalances. Interventions for correction encompass the administration of hypertonic saline (3% NaCl) for severe hyponatremia, cautious use of hypotonic fluids for hypernatremia, calcium gluconate for hypocalcemia, and intravenous dextrose for hypoglycemia. These targeted approaches address the specific electrolyte disturbances observed in patients diagnosed with FS due to electrolytic disorders. Upper respiratory tract infections were identified as the most prevalent etiology of fever among the participants in the research. This result aligns with other research that suggests respiratory tract infections, namely viral infections, are the prevailing cause of FS (31). Healthcare practitioners must possess knowledge regarding this correlation in order to administer suitable preventive and therapeutic interventions for youngsters afflicted with respiratory tract infections who are susceptible to FS. With regard to the diagnostic findings, a significant proportion of the patients had EEG results that were normal. This suggests that FS frequently do not manifest as observable irregularities in the electrical activity of the brain. This discovery aligns with prior research that has documented typical EEG readings in the majority of younger patients affected with FS (27-29). Nevertheless, a minority of the patients had atypical EEG characteristics, including epileptiform discharges or a sluggish background. A subset of children with FS may have an underlying propensity to epilepsy or other neurological disorders, according to these results; hence, additional assessment and follow-up are crucial.

Implications and actions needed

In general, this research makes a valuable contribution to the extant body of knowledge concerning FS by elucidating the attributes and risk factors that are linked to such episodes in pediatric patients residing in Jeddah, Saudi Arabia. The results emphasize the significance of acknowledging FS as a prevalent disorder in children, frequently manifesting as solitary incidents. Subsequent research is necessary to elucidate the underlying mechanisms and potential long-term consequences of the correlation between FS and developmental delay. It is imperative that healthcare professionals possess knowledge regarding prevalent precipitants of FS, including upper respiratory tract infections. By doing so, they can administer suitable interventions and educate parents and caregivers concerning the prevention and management of FS. It is critical to recognize and address the limitations inherent in this research.

Strengths and limitations

The limitations of this study include its retrospective which makes it susceptible to intrinsic constraints, including recollection bias and insufficient medical data including the specific domain of developmental delay. Furthermore, the research was carried out only within a single institution, perhaps constraining the applicability of the results to the wider populace. Subsequent investigations ought to strive to do prospective studies with control groups that encompass more substantial sample sizes and a broader demographic in order to delve deeper into the determinants of risk and enduring consequences linked to FS.

Conclusions

In conclusion, the research conducted on FS in pediatric patients in Jeddah, Saudi Arabia, yields significant contributions to our understanding of the attributes and risk factors linked to this particular medical illness. The results of this study add to the current body of knowledge regarding FS and emphasize the necessity for more investigations to gain a more comprehensive understanding of the fundamental mechanisms, long-term consequences, and risk factors linked to such conditions. Generalized seizures were more common than focal seizures, emphasizing the importance of distinguishing seizure types, as generalized seizures may indicate underlying structural brain anomalies that warrant further investigation. A significant link between FS and developmental delays was discovered, highlighting the need for additional research into the relationships and recommending routine developmental screenings in affected children. Upper respiratory tract infections emerged as the primary trigger for FS, indicating a critical area for preventive care through parental education on fever management and infection control. Although normal EEG results were prevalent, a minority of patients exhibited atypical findings such as epileptiform discharges, suggesting a predisposition to epilepsy, which warrants careful monitoring and follow-up. To improve clinical practice, it is crucial to provide ongoing training for healthcare providers on the latest FS research and management strategies, while also encouraging multicenter, prospective studies to explore the mechanisms and long-term outcomes of FS across diverse populations for broader applicability.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://pm.amegroups.com/article/view/10.21037/pm-24-35/rc

Data Sharing Statement: Available at https://pm.amegroups.com/article/view/10.21037/pm-24-35/dss

Peer Review File: Available at https://pm.amegroups.com/article/view/10.21037/pm-24-35/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://pm.amegroups.com/article/view/10.21037/pm-24-35/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics of King Abdulaziz University (No. 266-23) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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