Febrile seizures in one-five aged infants in tropical practice: Frequency, etiology and outcome of hospitalization.

BACKGROUND: Convulsive seizures are the common neurological emergencies in developing regions.
OBJECTIVES: The aim was to determine the prevalence, causes and outcome of seizures in childhood. PATIENTS AND METHODS: Participants were children aged 1-5 years old, admitted consecutively with a history of febrile convulsions or were presented seizures with fever during hospitalization, in two pediatric university hospitals. The prospective study covered a period from January to December 2013. At admission, emergency care and resuscitation procedures were provided according to the national guidelines. The history included the number and a parental description of seizures. Children with epilepsy, any central nervous system infections and other disease were excluded.
RESULTS: We have recorded 3647 children. Among them, 308 (8.4%) infants had presented with febrile seizures including 174 males and 134 females admitted to both pediatric hospitals (Tokoin University Teaching Hospitals: 206/3070, Campus University Teaching Hospitals: 102/577). Infants from 1 to 3 years age were the most common affected and constituted 65.9% of all patients. The months of September, December and January had recorded the high frequency of admission due to seizures. Regarding the seizures type, generalized tonic-clonic seizures were predominant (46.4%) followed by tonic seizures (17.2%) and status epilepticus in 9%. The etiologies were marked by falciparum malaria (52.3%), and other infections in 47.7%. At discharge, we have noted 11% (34/308) with neurodevelopmental disabilities, 6.7% of epilepsy and 9.7% (30/308) of death.
CONCLUSION: The febrile seizure in child younger 5 years is an indicator of severe malaria in tropical nations. The campaign for "roll back malaria" must continue in developing countries to avoid long-term gross neurological deficits.

Introduction

Worldwide, febrile seizures are the most common type of acute seizures in children.[123] Febrile seizures occur in 2–7% of individuals before age 5 years.[4567] The syndrome of febrile seizures is defined as seizures associated with fever in the absence of central nervous system (CNS) infection or acute electrolyte imbalance in a young child.[89] Differentiation of febrile seizures from acute symptomatic seizures secondary to CNS infection or seizures triggered by fever in children with epilepsy is essential. In tropical countries, seizures are common, but the prevalence of febrile seizures, which have a poorer outcome, may be higher than Western countries.[31011] Sepsis is the principal etiology in developed nations while malaria is the leading cause in sub Saharan Africa.[23512] Epidemiological and clinical studies have reported that most children with simple febrile seizures have normal development and intelligence.[131415] However, some children with complex febrile seizures are at risk for long-term neurodevelopmental and cognitive impairment in these regions.[58161718] This study aimed to determine the frequency, etiology and the outcome of febrile seizures among children admitted in two university pediatric hospitals.

Patients and Methods

Study participants

Participants were children (aged 1–5 years old), admitted with an incident of febrile convulsions or were presented seizures with fever during hospitalization, in two pediatric centers (Tokoin University Teaching Hospitals [TUTH] and Campus University Teaching Hospitals [CUTH]). The study covered a period of 1-year from 1 January to 31 December 2013. These pediatric services admit about 12,000 children (9000 in TUTH and 3000 in CUTH) <15 years annually. The both centers are the national referral hospital for children health.

Admission procedures

Study participants were recruited consecutively as they presented to hospitals. At admission, emergency care and resuscitation procedures (correction of hypoglycemia, hypovolemia, and oxygen and anticonvulsant therapy) were administered according to the national guidelines. Parents were then invited to sign a consent form to participate in the study. Children with epilepsy and any other disease or CNS infections were excluded. The history included the number and a parental description of seizures. Level of consciousness was determined using the Blantyre Coma Scale. Status epilepticus was defined as a seizure lasting 30 min or longer or as three or more seizures from which the patient did not regain consciousness after 1-h.[115] Febrile seizure was defined as seizures associated with fever (temperature ≥38°C) in the absence of CNS infection or acute electrolyte imbalance in a young child.[1] A sample venous blood was drawn for a full routine analyzes, and plasma from children with life threatening conditions was obtained for acid base status, electrolytes and creatinine. Severe anemia was defined as hemoglobin <50 g/L and metabolic acidosis as a base deficit >8. Hypokalemia was defined as plasma K+ <3.0 mmol/L, hyperkalemia as K+ >5.0 mmol/L, hyponatremia as Na+ <125 mmol/L and impaired renal function as plasma creatinine >80 μmol/L. Lumbar punctures were performed for all admissions according to a standard protocol except the contraindication cases to exclude any CNS involvement.[19] A child was said to have malaria as a primary diagnosis if she/he had asexual forms of Plasmodium falciparum parasites detected on blood films. Malaria was treated with parenteral quinine and in case of sepsis empirical antibiotic treatment was given.

The Medical Research Institute of the university hospital had approved the present study.

Results

We have recorded 3647 children. Among them, 308 (8.4%) infants aged one to 5 years had presented with febrile seizures including 174 males and 134 females admitted to both pediatric hospitals (TUTH: 206/3070, CUTH: 102/577). Infants from 1 to 3 years age were the most common affected and constituted 65.9% of all patients. The months of September, December and January had recorded the high frequency of admission due to seizures. Regarding the seizures type, generalized tonic-clonic seizures were predominant (46.4%) followed by tonic seizures (17.2%) and status epilepticus (9%). The etiologies were marked by falciparum malaria (52.3%), and other infections (bacterial meningitis, eruptive fever, respiratory tract infections and gastroenteritis) in 47.7%. At discharge, we have noted 11% (34/308) with neurodevelopmental disabilities, 6.7% of epilepsy and 9.7% (30/308) of death. Table 1 showed the demographic and clinical parameters of infants. Figure 1 had presented the monthly distribution of admissions of children with febrile seizures.

Table 1

Demographic and clinical features of children with febrile seizures

Figure 1

Monthly distribution of admission in children with febrile seizures

Discussion

Methodology

This prospective study was conducted in two pediatrics university teaching hospitals in the urban area. The study focused on children aged 1–5 years old with febrile seizures but had some weakness. Some children who died while being transferred from home to hospital were not included. We were unable to collect patients who could not afford care facilities or were more likely to attend basic hospitals or traditional healers. Some parents were not able to give all information regarding birth history and seizures description. Added to this, relatives had more difficulties to honor specific analyzes requested and bought drugs. All these recruitment bias had reduced the sample size. These findings may not reflect the real frequency of febrile seizures in the whole country. However, the consistency of our results with previous studies provides some validity to the data.

Frequency, age, sex and monthly distribution of febrile seizures

The frequency of febrile seizure is 8.4%, much lower than 26.2% reported in 1995 at the University teaching hospital of Kara,[18] but similar to that reported in industrialized countries.[147] In developed nations, febrile seizures occur in 2–8% of children before age 5 years.[14678] In sub Saharan Africa, febrile seizures occur in the average of 16% ±11% and a maximum of 38%.[3] In Ethiopia, one hospital based study found an incidence of 13.6 per 1000 live births, and in Kenyan rural children, the incidence was 95 per 100,000/year in children <5 years.[2021]

This reduction in the prevalence of febrile seizures may be partly the result of improved in the early management and especially the education of the population to change behavior towards child with fever and convulsions. Another reason of reduction of the prevalence can be the result of multiple campaigns against malaria conducted by government and health associations. However, many efforts remain to be done in poor resources nations to improve children health care.

Febrile seizures were more common in children younger than 5 years (77.3%), with a peak around 1–3 years. The male predominance was reported by several authors with rates ranging from 55% to 56%, respectively.[19192223]

Regarding the monthly distribution of seizures, an increase was observed between September and January, with 61.22% of cases whereas in other country, seizures increased in frequency from August to March.[24] These peaks were closely related to the impact of malaria at its high transmission period in the rain season of the year in our region.

Clinical forms of convulsions

The clinical seizures-type in the child is highly polymorphic. We identified 46.4% of generalized tonic-clonic seizures (GTCS), 17.2% of tonic seizures and status epilepticus was noted in 9% of cases, rates similar to those reported in previous study,[17] but less than those from some regions of world where GTCS occurred in 65–99%.[1141525] For several authors, there is a controversy whether tonic-clonic seizures are more common than tonic seizures in children with febrile seizures.[111420] GTCS form still prominent in infant and child whereas focal seizures occur frequently in newborns.[2026]

Etiology of febrile seizures

The combination of fever and convulsions in infants is one of the most common emergency in the tropical countries.[3424] The febrile convulsions constitute more than half (65.4% of admissions) of seizures occurring in children. The main diseases associated with seizures in the context of high temperature were infections, including severe falciparum malaria (52.3%) and bacterial meningitis (14.9%). Hypoxic/ischemic encephalopathy, prematurity, twinning and family history of epilepsy was reported as risk factors for febrile seizures. In this study, 60.4% of patients had no antecedent history (personal and family), which could be taken as a risk factor. In tropical African nations, falciparum malaria remains the dominant etiology of febrile seizures and neurological emergencies in children as reported by several authors in previous studies.[35212227] In Maghreb region, Europe and Japan, the etiologies were respiratory tract infections, eruptive fevers or gastroenteritis.[1928] Early management of any acute fever in the tropical countries is a major means to prevent febrile convulsions and later life epilepsy and neurodevelopmental disabilities.

Outcome of febrile seizures

The treatment of convulsions is both symptomatic and etiologic. The prognosis depends on the etiology and severity of seizures. In this study, symptomatic treatment was conducted with diazepam and phenobarbital. At discharge, 30 cases (9.7%) of psychomotor retardation with epilepsy, and 11% of deaths were noted among children with febrile seizures. Long-term follow-up of infants suffering from febrile seizures is marked by epilepsy, neurodevelopmental and cognitive impairment and behavioral disturbance.[5121820,29] Safety outcome needs good behavior changing towards malaria prevention and appropriated management of children with febrile seizures.

Conclusion

Febrile seizures prevalence is going down in children <5 years in our country. It is dominated by generalized tonic-clonic seizures. The outcome is marked by gross neurodevelopmental and cognitive disabilities. This low prevalence must be kept down by improving care facilities and strengthen caregiver's capacities to avert long-term neurological impairment.