Article Figures & Data
Figures
- Fig. 1.
Recruitment of the study participants.
- Fig. 2.
Events terminating follow-up time at risk (see “Methods,” Statistical Analysis).
- Fig. 3.
Cumulative probability over time of a first febrile seizure recurrence by treatment group (intention to treat).
Tables
Ibuprofen n = 111 (100%) Placebo n = 119 (100%) Demographic characteristics Female gender 41 (37%) 49 (41%) Age at study entry1-a 1.9 (1.4–2.4) 1.9 (1.4–2.7) First-degree family history of febrile seizures* 27 (24%) 32 (27%) Family history of any seizures 44 (40%) 49 (41%) Day-care attendance 39 (35%) 49 (41%) First born 70 (63%) 59 (50%) Caucasian origin 67 (60%) 78 (66%) Immunization completed1-b 85 (77%) 88 (74%) Initial seizure characteristics Age at onset1-a 1.4 (1.1–1.9) 1.5 (1.0–2.1) FSE1-c 8 (7%) 12 (10%) Focal type1-d 16 (14%) 10 (8%) Multiple type1-e,* 47 (42%) 40 (34%) Rectal temperature below 40.0°C* 55 (50%) 66 (56%) Previous recurrent febrile seizures Previous recurrent febrile seizures* 39 (35%) 45 (38%) Time lapse between last seizure and study entry1-a 0.10 (0.05–0.21) 0.07 (0.04–0.18) Number of risk factors 1 66 (60%) 66 (56%) 2 33 (30%) 44 (37%) ≥3 12 (11%) 9 (8%) ↵F1-a In years, median (25th–75th percentiles).
↵F1-b According to the national guidelines for immunization in the Netherlands.
↵F1-c Febrile status epilepticus, seizure duration ≥30 min.
↵F1-d Focal onset of the seizure or postictal Todd's paresis.
↵F1-e Seizure recurrence within 24 hours.
↵* Risk factor for febrile seizure recurrence discussed in “Patients”.
Ibuprofen n = 271 (100%) Placebo n = 284 (100%) Fever episodes without febrile seizure recurrence Fully compliant 164 (61%) 183 (64%) Not fully compliant Parents did not give the study medication and did not report fever promptly 17 (6%) 6 (2%) Parents deviated from the prescribed dose: 54 (20%) 56 (20%) and gave additional acetaminophen 4 (1%) 3 (1%) and gave diazepam rectal solutiona 1 (<1%) – Fever episodes with febrile seizure recurrence Fully compliant 13 (5%) 17 (6%) Not fully compliant Parents did not give the study medication, because fever was not recognized
before the seizure occurred11 (4%) 11 (4%) Parents did not give the study medication for other reasons 7 (3%) 8 (3%) * Administered of the parents' own accord to prevent febrile seizure recurrence.
Note: Antibiotic treatment for suspected bacterial infection of the respiratory tract was prescribed for 8 children (1 in the ibuprofen group and 7 in the placebo group). Two children received continuous antibiotic prophylaxis because of preexisting vesicoureteral reflux (1 in the ibuprofen group vs 1 in the placebo group).
Ibuprofen Group Placebo Group All fever episodes 271 284 At fever onset 39.1 (38.7–39.4) 39.0 (38.7–39.3) At 6 (±2) hours after fever onset 38.2 (37.3–39.0) 38.9 (38.2–39.3) Fever episodes with recurrence Intention-to-treat analysis 31 36 At fever onset 39.0 (38.7–39.7) 39.4 (38.8–39.7) At febrile seizure recurrence 39.9 (39.0–40.3) 39.6 (39.1–40.0) Per-protocol analysis 13 17 At fever onset 39.0 (38.6–39.1) 39.5 (38.7–39.8) At febrile seizure recurrence 40.1 (39.9–40.4) 40.0 (39.4–40.3) Note: Median temperatures, Celsius (25th–75th percentiles).
- Table 4.
Previous Randomized Controlled Studies of Prevention of Febrile Seizure Recurrences, Including Antipyretic Treatment
Camfield, 1980 Schnaiderman, 1993 Uhari, 1995 Treatment groups (number of children) Single daily dose of phenobarbital per os 5 mg/kg plus antipyretic instruction of the parents (n = 39) versus antipyretic instruction including oral antipyretics only (n = 40) Prophylaxis of acetaminophen orally 15–20 mg/kg per 4-hourly dose (n = 53) versus sporadic usage of acetaminophen of a similar oral dose contingent at fever >37.9°C (n = 51) Diazepam 0.2 mg/kg 8-hourly during fever >38.5°C (n = 81), of which the first dose to be given rectally and additional doses per os, versus placebo (n = 80); additional: cross-over per fever episode with acetaminophen 10 mg/kg 6-hourly during fever >40.0°C (route of administration not reported) versus placebo Temperature measurements Oral and rectal measurements by the parents at home Rectal measurements by nurses or parents during hospitalization Measurements by the parents at home (oral or rectal) Outcome measure First febrile seizure recurrence in the same or following fever episodes First febrile seizure recurrence in the same fever episode (multiple type) Number of febrile seizure recurrences in any of the following fever episodes Body temperature Body temperature Maximum study duration 12 mo One fever episode 2 y Patient inclusion Simple initial febrile seizure Simple initial febrile seizure Simple or complex initial febrile seizure Major difficulties in the evaluation of the results No standardization of the antipyretic treatment4-a No placebo control group of antipyretic treatment No standardization of the antipyretic treatment4-b No placebo control group of antipyretic treatment Noncomparable outcome measure Results 2 of the 39 patients using phenobarbital plus antipyretic instruction and 10 of the 40 patients with only instruction had a recurrent febrile seizure4-c 4 of the 53 children using ongoing prophylaxis vs 5 of the 51 children in the sporadic-use group had a recurrent seizure in the same fever episode 9 of the 173 fever episodes were associated with a recurrence in the acetaminophen group vs 14 of the 170 fever episodes in the placebo group4-d Efficacy of antipyretic preventive treatment as concluded Not effective Not effective Not effective ↵F4-a All parents received instructions about fever control; no standardized dose per kilogram of bodyweight was administered.
↵F4-b All parents were allowed to administer extra antipyretics whenever they believed they should.
↵F4-c Survival analysis was performed to compare seizure recurrence in the phenobarbital-plus-instruction group and the instruction-only group (P < .02, log-rank).
↵F4-d Survival analysis was performed to compare seizure recurrence in the diazepam group and the placebo group (P = .41, log-rank).
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