This was a single-center, longitudinal cohort study. Vietnamese children were
prospectively identified for their first febrile seizures (FS) through the General
Pediatric Department and Neurology Department of Children's Hospital 2 in Ho Chi Minh
City between March and December 2023. This hospital is one of the largest tertiary
pediatric hospitals in southern Vietnam with 1,400 beds, and receives about 90,000
admissions every year, with 800-1,000 cases of initial FS. After recruitment, the
participants have been monitored for an average of two years to determine whether they
experience recurring FS or develop epilepsy.
Sample size and sampling:
The sample size was calculated using a specific formula to estimate the incidence of FS
recurrence in the cohort study. With the desired confidence level of 95%, an estimated
error of 0.1, and an expected incidence of 31.8% based on a similar study conducted by
Berg, the minimum sample size required was determined to be 385 participants. The sample
size was also estimated based on the number of events per predictor in regression models,
with at least 10 events per predictor recommended by Peduzzi et al. For the recurrent FS
outcome, we have 12 potential predictor variables including age of onset, male gender,
prematurity, low birth weight, neurodevelopmental abnormality, family history of FS or
epilepsy, temperature, duration of fever at the time of the seizure, and characteristic
of the first FS such as semiology, duration and number of seizures during the illness
yielding approximately 120 cases to achieve the required sample size for estimating
recurrence of FS. Besides that, we also have 16 potential predictor variables for the
subsequent epilepsy outcome, including the above factors adding to the number of FS, and
characteristics of all FS (first and recurrences). As such, we aimed to obtain at least
160 children. Finally, the overall sample size required at least 385 patients.
Convenience sampling was applied to recruit the participants. In detail, every weekday,
the list of inpatient reports of the General Pediatric Department and Neurology
Department on the electronic medical record database of Children's Hospital 2 was used to
identify all children who had been diagnosed with FS and admitted to these departments.
The investigator met with these children's parents or caregivers and asked a series of
screening questions to confirm that they had not previously experienced febrile or
unprovoked seizures. If the child had such a history, they were excluded from the study.
The patients were then followed up until they recovered and were discharged from the
hospital. At this point, the investigator made the final diagnosis of the first FS and
assessed whether any exclusion criteria applied. If the patients were eligible for the
study, the investigator obtained informed consent from their parents and proceeded to
gather study data.
Data collection
The standardized questionnaire solicited child-related data including the age of onset,
gender, perinatal history (i.e. age of gestation, birth weight, asphyxia, hospitalization
at the neonatal intensive care unit), medical history (previous neurological diseases),
family history of FS and epilepsy (including first relative and any relative);
seizure-related data including semiology, duration, and number of seizures during the
illness; and illness-related data including temperature, duration of fever at the time of
the seizure, and the cause of fever. The interviewer obtained a comprehensive description
of the seizure from either the parent or, if unavailable, from an eyewitness.
Descriptions were compiled from both medical records and interviews, and additional
clarification was sought, if necessary, by contacting the parent or witness again.
Particular note was taken of the presence of asymmetrical features involving a unilateral
arm, leg, or face (or some combination) or an eye deviation to one side, even if the fit
later became bilateral tonic-clonic. Those seizures were classified as focal-onset
seizures according to the ILAE classification in 2017. The presence of Todd's paresis
(paralysis of one limb or one side of the body or a gaze palsy in the immediate postictal
period) was considered indicative of a focal seizure. The study used medical records to
gather information on seizures, associated symptoms, diagnosis, and temperature.
At the time of the first FS, a detailed neurologic examination and Denver II
developmental screening test were conducted by a pediatrician. Test Denver II is a scale
to assess the psychomotor development of children under 6 years old, which is validated
and used in clinical practice in Vietnam. Test Denver II is a fairly comprehensive
assessment of child development and focuses on 4 areas: personal-social, fine
motor-adaptive, language, and gross motor. The interpretation of the test results
indicates an obvious developmental delay if there are delayed items in at least two
areas, with each area having a minimum of two items. A child is considered to have a
suspected developmental delay if there are delayed items in one area with at least two
items. If there are no signs of suspected or delayed development as described above, the
child is considered normal. Developmental Quotient (DQ) is a calculation that reflects
the rate of development in any given area and represents the percentage of normal
development present at the time of testing.
Developmental Quotient (DQ)= (Developmental age (DA))/(Chronological age (CA)) x 100%
Lumbar puncture was performed only in cases that were indicative of meningitis or
encephalitis, whereas neuroimaging (computerized tomography [CT] or magnetic resonance
imaging [MRI]) was performed on children with focal seizures, febrile status epilepticus,
or abnormal neurologic examination. Children who experience their first FS in our setting
usually do not undergo an electroencephalography (EEG).
Following the initial interview, parents were contacted every three months to determine
whether their child had experienced any further seizures and the circumstances under
which they occurred. If a febrile seizure recurs or an afebrile seizure occurs, parents
can report it immediately and directly to the investigator. Descriptions of the recurrent
seizures were obtained in the same manner as for the initial FS. Whenever possible, we
also obtained documentation of the recurrence from the medical record. Our goal was to
follow children for an average of two years from the initial FS. We considered a seizure
unprovoked if there were no acute precipitating circumstances to which the seizure could
reasonably be attributed. According to the ILAE practical clinical definition from 2014,
epilepsy is characterized by having two unprovoked seizures that are more than 24 hours
apart. Children were censored from further analysis if they experienced an unprovoked
seizure or were lost to follow-up.
Ethical considerations
The study protocol was approved by the Ethical Committee of Children's Hospital 2 (124/
GCN-BVNĐ2). and written consent was obtained from all participants. Informed consent was
obtained from all study participants and their parents/caregivers.