Retrospective studies | Population | Etiology | Treatment | Add-on therapy | Outcome |
---|---|---|---|---|---|
Abend et al. [38] | N = 23 late preterm and term | N = 8 HIE N = 4 genetic N = 3 malformative N = 3 infections N = 2 cryptogenic N = 2 stroke N = 1 tumor | N = 18 PHB (dose: N/A) N = 1 PHE (dose: N/A) N = 4 LEV (10–20 mg/kg) | N = 13 LEV as 2nd line (dose: N/A) N = 5 LEV as 3rd line | Seizure cessation in 7/23 (30%); seizure reduction (> 50%) in 1/23. |
Khan et al. [39] | N = 22 term | N = 12 HIE N = 2 IVH N = 2 CNS infections N = 6 various | N = 16 PHB (dose: N/A) N = 3 LEV (dose: N/A) | N = 19 received LEV as 2nd (N = 16), 3rd (N = 2) or 4th (N = 1) line | 7 of 22 patients (32%) achieved complete cessation of seizures after administration of the loading dose, 14 (64%) achieved cessation of seizures by 24 h, 19 (86%) by 48 h, and all 22 (100%) by 72 h |
Khan et al. [40] | N = 12 preterm | N = 5 HIE N = 3 IVH N = 3 N/A N = 1 HSV encephalitis | N = 9 PHB (dose: N/A) N = 3 LID (dose: N/A) | N = 12 LEV (dose: N/A) | 4 patients (36%) reached seizure cessation after the loading dose, 9 (82%) by 24 h, 10 (91%) by 48 h, and 10 subjects (91%) by 72 h. |
Rakshabhuva- nkar et al. [41] | N = 8 term and preterm | N = 5 HIE N = 2 IVH N = 1 N/A | N = 8 PHB (dose: N/A) N = N/A PHE (dose: N/A) | N = 8 LEV (10 mg/kg) | LEV’s effectiveness in 6/8 patients. |
Lo Yee Yau et al. [42] | N = 12 preterm and term | N = 6 HIE N = 3 CNS infections N = 1 hypoglicemia N = 2 metabolic | N = 12 PHB (dose: N/A) | N = 8 MDZ as 2nd line AED and LEV as 3rd line. N = 4 were given LEV as 2nd line AED. | LEV’s efficacy: 75% of patients treated. No side effects reported. |
Maljevic et al. [43] | N = 10 | KCNQ 3 mutations | N = 1 PYR N = 2 LEV N = 1 OXC | N = 1 LEV (65 mg/kg) N = 1 OXC (20 mg/kg) | 1 was seizure free after one dose of LEV. 1 was seizure free after day 20 on LEV. 1 was seizure free on OXC. |
Shin et al. [44] | N = 18 term and preterm | N = 12 HIE N = 1 CNS N = 1 IVH N = 4 malformative | N = 18 PHB or PHE (dose: N/A) | N = 18 LEV after PHB failure (N = 1 only LEV N = 11 LEV + PHB N = 6 PHE + LEV) | 94% of patients had seizure cessation within the first week from LEV’s introduction, and 89% remained seizure-free under LEV monotherapy at 1 month. |
Han et al. [45] | N = 37 preterm | N = 15 HIE N = 6 GMH N = 14 IVH N = 1 malformative N = 1 meningitis | LEV (40–60 mg/kg) | N = N/A PHB (20 mg/kg) N=N/A PHE, MDZ, TPM, VPA as 3rd line. | Seizure cessation in 21 patients (57%) with LEV alone. Seizure cessation in 9 infants (24%) after LEV + PHB. 7 required third-line AED. |
Venkatesan et al. [46] | N = 32 term | HIE | N = 23 PHB N = 2 LEV N = 2 MDZ (doses: N/A) | N = 23 LEV as 2nd line N = 2 LEV as 3rd line after PHB and MDZ failure | 84% of the patients treated with LEV achieved seizure cessation within 72 h. |
Rao et al. [47] | N = 44 term | HIE | N = 23 PHB N = 2 LEV | N = 10 LEV as 2nd line | 50% of patients treated with levetiracetam became seizure-free after 40 h, and 100% achieved seizure freedom between 100 and 120 h. |
Van der Broek et al. [48] | N = 31 term | HIE | N = 31 PHB (20 mg/kg) | / | PHB’s efficacy: 66%. |
Boylan et al. [49] | N = 14 term and preterm | N = 4 HIE N = 3 IVH N = 3 metabolic N = 1 meningitis N = 3 mild asphyxia | N = 14 PHB (20–40 mg/kg) | N = 4 CLZ N=N/A PHE (doses: N/A) | PHB was only effective in 29% of patients, those with normal background EEGs or mild to moderate background abnormalities and low seizure burden. |
Spagnoli et al. [50] | N = 91 term and preterm | N = 45 HIE N = 21 IVH N = 4 malformative N = 12 metabolic disorders N = 4 CNS infection N = 1 genetic N = 4 N/A | N = 91 PHB (20 mg/kg) | N = N/A PHE 20 mg/kg as 2nd line N = N/A MDZ 0.15 mg/kg as 3rd line | PHB was effective alone in 62.6% of patients. |
Hakeem et al. [51] | N = 11 term and preterm | N = 6 HIE N = 3 IVH N = 1 CNS N = 1 N/A | N = 2 oral cloral hydrate (30 mg/kg) N = 7 PHB (20 mg/kg) N = 2 DZP (1 to 2 mg iv bolus) | N = 1 CLZ c.i. (10 mcg/kg/hr) | 6/7 responded to PHB but 4/7 later relapsed. |
Weeke et al. [52] | N = 413 (N = 319 term, N = 94 preterm) | N = 228 HIE N = 45 HIE N = 32 PAIS N = 40 CNS infections N = 100 others | N = 413 PHB (dose: 20 mg/kg) | N = 186 LID as 2nd line N = 172 LID as 3rd line | In term infants, a response to LID was seen in 72.5–80%, with cessation of seizures and no need for rescue AED in 21.4–67.6%. Lower response rate in preterm (55.5–58.2% with cessation of seizures and no other AED in only 16.4–40.7%). |
Lundqvist et al. [53] | N = 30 term | N = 18 HIE N = 4 meningitis N = 6 PAIS N = 1 hypoglicemia N = 1 uncertain | N = 17 DZP (dose: N/A) N = 8 MDZ (dose: N/A) N = 5 DZP + MDZ (dose: N/A) | N = 30 LID | LID’s efficacy: 65%. |
Van der Broek et al. [54] | N = 22 term | HIE | N = 22 PHB (dose: N/A) | N = 22 MDZ (dose: N/A) N = 22 LID (dose: 2 mg/kg, followed by 4 mg/kg/h c.i.) | 20/22 (90%) newborns responded to LID. No cardiac arrythmias were reported (91%) |
Jennekens et al. [55] | N = 11 term | N = 11 stroke | N = 11 PHB (20 mg/kg) | N = 8 MDZ as 2nd line N = 9 LID as 3rd line | In term newborns with PAIS, MDZ and LID induce a shift from lower to higher frequency electrocortical activity. Compared to LID, MDZ reduced more pronouncedly the total EEG power. |
Shany et al. [56] | N = 30 term | N = 30 HIE | N = 30 DZP or PHB | N = 22 LID as 2nd line N = 8 MDZ as 2nd line | 77% response rate to LID. |
McDermott et al. [57] | N = 10 term | HIE | N = 5 LRZ N = 4 PHB or PHE (20 mg/kg) N = 1 PHB (20 mg/kg) | N = 5 LRZ as 2nd line | Administration of a single dose of LRZ stopped seizures in all neonates. 4 neonates receiving simultaneously PHB and/or PHE had no further seizures. 6 had seizure recurrence. |
Castro Conde et al. [58] | N = 13 term and preterm | N = 7 HIEN = 3 stroke N = 2 IVH N = 1 N/A | N = 32 PHB (20 mg/kg tritated up to 40 mg/kg) followed by PHE as 2nd line AED (20 mg/kg) | N = 13 MDZ as 2nd (9/13) or 3rd (4/13) line AED in non-responders. | Ten of 13 neonates with SE treated with midazolam were electrically controlled in the first hour of treatment. |
Vilan et al. [59] | N = 9 term | KCNQ2 mutations | N = 9 PHB | N = 8 PYR, N = 6 LID, N = 6 MDZ, N = 3 CZP, N = 3 LEV, N = 2 PHE, N = 2 VPA, N = 2 CBZ, N = 1 TPM | PH and PYR (used in 8/9 patients) were ineffective. 2 patients were SF during LID infusion and were later switched to oral PHT or oral CBZ. |
Montesclaros Hortigüela et al. [60] | N = 13 G.A. = N/A | KCNQ2 mutations | N = 10 PHB N = 2 LEV N = 1 MDZ (doses: N/A) | Several AED were administered as 2nd line: CBZ, LEV, MDZ, VPA, PHE, TPM, VGB, LID, OXC, PYR | 5/9 were seizure free but with severe impairment in psychomotor development in treatment with CBZ (n = 2), VPA + CBZ + LCM (n = 1), PHB + VPA + OXC (n = 1), OXC + TPM (n = 1). |
Pisano et al. [61] | N = 15 term | KCNQ2 mutations | Multiple AEDs (including PHB as first-line AED, VPA, steroids) were tried unsuccessfully | N = N/A CBZ (20 mg/kg/day) N = N/A PHE (dose widely ranging) | 53% of the patients were seizure-free on CBZ; 33% responded to PHE; the remaining 47% of the patients responded to TPM and LEV. |
Sands et al. [62] | N = 19 term | SLC13A5 mutations (KCNQ2 gene) | N = 13 PHB (dose: N/A) N = 4 CBZ (10 mg/kg) | N = 15 CBZ (10 mg/kg) | CBZ’s efficacy: 89%. |
Singh et al. [63] | N = 10 term | N = 8 HIE N = 2 unknown | N = 10 CBZ (dose: 10 mg/kg) | N = 2 DZP | Seizure control in 80% of patients on CBZ; 2 patients needed DZP as 2nd line. |
Glass et al. [64] | N = 6 term | HIE | N = 5 PHB (30–60 mg/kg) | N = 5 TPM (10 mg/kg) | 3/5 patients treated with TPM had seizure reduction or cessation. One adjunctive patient achieved seizure freedom on TPM at 6 months. |