DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY SYSTEMATIC REVIEW

Prednisolone/prednisone as adrenocorticotropic hormone

alternative for infantile spasms: a meta-analysis of randomized
controlled trials
SHAOJUN LI 1,2,3,4,5 | XUEFEI ZHONG 2,3,4,5,6 | SIQI HONG 2,3,4,5,7 | TINGSONG LI 2,3,4,5,7 | LI JIANG 2,3,4,5,7
1 Department of Emergency, Children’s Hospital of Chongqing Medical University, Chongqing; 2 Ministry of Education Key Laboratory of Child Development and
Disorders, Children’s Hospital of Chongqing Medical University, Chongqing; 3 National Clinical Research Center for Child Health and Disorders (Chongqing), Children’s
Hospital of Chongqing Medical University, Chongqing; 4 China International Science and Technology Cooperation Base of Child Development and Critical Disorders,
Children’s Hospital of Chongqing Medical University, Chongqing; 5 Chongqing Key Laboratory of Paediatrics, Children’s Hospital of Chongqing Medical University,
Chongqing; 6 Department of Electroneurophysiology, Children’s Hospital of Chongqing Medical University, Chongqing; 7 Department of Neurology, Children’s Hospital
of Chongqing Medical University, Chongqing, China.
Correspondence to Tingsong Li, Department of Neurology, Building 6, Zhongshan Er Road 136, Yuzhong District, Chongqing 400014, China. E-mail: litscq@126.com

This article is commented on by Kelley on pages 540–541 of this issue.

PUBLICATION DATA AIM To compare the efficacy and safety of prednisolone/prednisone and adrenocorticotropic
Accepted for publication 26th November hormone (ACTH) in the treatment of infantile spasms using a meta-analysis of randomized
2019. controlled trials (RCTs).
Published online 5th January 2020. METHOD In a systematic literature search of electronic databases (MEDLINE, Embase, the
Cochrane Library), we identified RCTs that assessed prednisolone/prednisone compared with
ABBREVIATIONS ACTH/tetracosactide in patients with infantile spasms. The electroclinical response and
ACTH Adrenocorticotropic hormone adverse events were evaluated.
RCT Randomized controlled trial RESULTS Six RCTs (616 participants) were included in the meta-analysis. Compared with
prednisolone/prednisone, ACTH/tetracosactide was not superior in terms of cessation of
spasms at day 14 (relative risk 1.19, 95% confidence interval [CI] 0.74–1.92), day 42 (relative
risk 1.02, 95% CI 0.63–1.65), and resolution of hypsarrhythmia on electroencephalogram
(relative risk 1.14, 95% CI 0.71–1.81); the incidences of common adverse reactions caused by
ACTH/tetracosactide were not lower than that of prednisolone/prednisone for irritability
(relative risk 0.79, 95% CI 0.57–1.10), increased appetite (relative risk 0.78, 95% CI 0.57–1.08),
weight gain (relative risk 0.86, 95% CI 0.56–1.32), and gastrointestinal upset (relative risk 0.60,
95% CI 0.35–1.02), though it seemed less frequent.
INTERPRETATION Prednisolone/prednisone elicits a similar electroclinical response as ACTH
for infantile spasms, which indicates that it can be an alternative to ACTH for treating
infantile spasms.

Infantile spasms, also called West syndrome, are character-
ized by the electroclinical triad of epileptic spasms, neu-
rodevelopmental delay, and hypsarrhythmia on
electroencephalogram (EEG).1 The estimated incidence
and prevalence of infantile spasms is 2 to 3 per 10 000 live
births and 0.015 cases per 1000 population respectively.2,3
Corticosteroids and adrenocorticotropic hormone (ACTH)
have been used for treating infantile spasms since the late
1950s.4 Since then, despite a series of randomized con-
trolled trials (RCTs) comparing corticosteroid and ACTH
effectiveness, conclusions have remained inconsistent.5 One
study found 86.6% and 28.6% electroclinical remission
with ACTH and prednisone respectively, demonstrating
ACTH to be more effective than corticosteroids.6 In 2012,
the American Academy of Neurology recommended
ACTH as first-line medication for infantile spasms,7 which
was confirmed by the International League Against Epi-
lepsy in 2015.1 In contrast, accumulating evidence from
the past decade suggests similar effectiveness of high-dose
corticosteroids for infantile spasms.5 Further, high-dose
prednisolone was included as one of three recommended
treatments (in addition to ACTH and vigabatrin) in the
2017 Quality Measure Set from the American Academy of
Neurology and Child Neurology Society.8 As reduced
lead-time to treatment can be more beneficial for out-
come,9 and given the limited accessibility and relatively dif-
ficult administration of ACTH, especially in low- and
middle-income countries,10 systematic evaluation of
ACTH and corticosteroids effectiveness is urgently
needed.
More RCTs on the comparative efficacy of cortico-
steroids and ACTH in cohorts with infantile spasms have
been published recently. We systematically reviewed and
analysed the literature on hormonal treatment of infantile
spasms, and then explored whether corticosteroids can be a
substitute for ACTH.

© 2019 Mac Keith Press DOI: 10.1111/dmcn.14452 575

METHOD
Criteria for considering studies
Type of study and participants
RCTs of any publication type were considered for inclusion.
Patients with a clearly stated diagnosis of infantile spasms
were included regardless of whether the typical hypsarrhyth-
mia EEG pattern was present. The exclusion criteria were as
follows: age at onset less than 2 months, children with Len-
nox–Gastaut syndrome that frequently followed infantile
spasms, and hormone treatment introduced before the trial.
No language restrictions were applied.
Type of intervention
RCTs that compared prednisone/prednisolone with
ACTH/tetracosactide were considered for inclusion. The
effects of prednisone were deemed equivalent to pred-
nisolone at equal doses because both result in equal serum
concentrations of prednisolone,11 which is the active form
in the human body.
Efficacy measures
Complete cessation of spasms on or between days 14 and 42
after the treatment; resolution of hypsarrhythmia on EEG.
Safety and tolerability measures
Adverse effects were documented.
Search methods for identifying eligible studies
We performed a systematic search of MEDLINE (1950 to
February 2019), Embase (1974 to February 2019), and the
Cochrane Central Register of Controlled Trials (CEN-
TRAL, issue 1, 2019), using the following terms: ‘spasms’
OR ‘infantile’ OR ‘West syndrome’ OR ‘hypsarrhythmia’
OR ‘infantile spasms’ AND ‘prednisone’ AND ‘pred-
nisolone’ AND ‘dexamethasone’ AND ‘ACTH’ AND ‘te-
tracosactide’. The references listed in the included trials
and relevant reviews were checked. We also searched Clin-
icalTrials.gov to cover additional studies. A detailed study
protocol has been uploaded to PROSPERO
(CRD42018109201).
Data extraction and risk of bias assessment
TL and SL screened all included studies independently.
The abstracts, data integrity, references, and methodologi-
cal quality were extracted and evaluated using a data
abstraction form. If data were incomplete, we emailed the
authors for supplementary information. The risk of bias
and methodological quality were assessed by using the
Cochrane Risk of Bias Tool. Disagreement was resolved
through consensus or referred to a third investigator (LJ).
Statistical analysis
For the meta-analysis we used Review Manager Software
(RevMan 5.3, Copenhagen, Denmark), obtained from the
Cochrane Collaboration. For dichotomous outcomes, the
Mantel–Haenszel method was applied to estimate the rela-
tive risk and 95% confidence interval (CI). Relative risk
576 Developmental Medicine & Child Neurology 2020, 62: 575–580
What this paper adds
• Prednisolone/prednisone is as effective as adrenocorticotropic hormone
(ACTH) in electroclinical response of infantile spasms.
• Prednisolone/prednisone and ACTH cause similar and tolerable adverse
effects, whose incidences are comparable.
• High-dose prednisone/prednisolone might be preferable to low dose for
achieving freedom from spasms.
means the ratio of risk for ACTH divided by the risk for
prednisolone/prednisone. For continuous outcomes,
inverse variance was used to estimate the standard mean
difference with 95% CI. Statistical heterogeneity was
quantified by the Mantel–Haenszel v2 test and the I2 statis-
tic. Significant heterogeneity was suggested where p<0.10
or I2>50%. The subgroup analysis was disaggregated by
prednisone/prednisolone dose and types of participant in
individual trials or set of eligible trials. In the case of sig-
nificant heterogeneity, a random-effects model was applied
for data analysis; while a fixed-effects model was conducted
in the case of non-significant heterogeneity. Publication
bias was estimated using Egger’s test with Stata software
(version 14, StataCorp, College Station, TX, USA).
RESULTS
Search results
From 2177 potentially relevant reports retrieved by the
electronic search, 1654 unique studies remained after elim-
ination of duplication. On the basis of the inclusion crite-
ria, 1634 studies were excluded after the review process.
After full-text articles were assessed, 13 trials were
excluded for reasons of non-randomization, no infantile
spasms, or insufficient data (Fig. S1, online supporting
information). Ultimately, seven RCTs published from
1983 to February 2019 were selected for inclusion in the
present study (Table 1).6,12–17 The sample size of the
RCTs ranged from 24 to 377 (mean 101). Among them,
only one trial included more than 100 cases,15 and two tri-
als involved the same cohort comprising 97 participants
(Table 1).16,17
Study characteristics
The six RCTs involved a total of 616 participants with
infantile spasms. Despite the fact that participants in the
two studies were from the same cohort, different outcomes
were measured separately.16,17 Two studies were multi-
centre,14,15 and the other five were single-centre stud-
ies.6,12,13,16,17 Seven RCTs provided the detailed aetiolo-
gies of infantile spasms.6,12–17 Five studies excluded
infantile spasms associated with tuberous sclerosis.12,14–17
Two trials administered the low-dose prednisone dose
(2mg/kg/d),6,13 while the other five trials administered
high-dose prednisolone (4mg/kg/d or 40–60mg/d; Table 1).
Assessment of risk of bias
For study quality, risk of bias was assessed in six RCTs
included in the meta-analysis.6,12–15,17 Among them, 1 out
of 6 had incomplete outcome data, 3 out of 6 were
 Table 1: Descriptive characteristics of the included studies

Cases Age Sex Follow Attrition

Study Country Study set Time frame (n) (mo) (M/F) Patients Interventions Study outcomes up (%)

Hrachovy et al.13 USA Double-blind, RCT NA 24 3.5–24 NA IS with HS ACTH (20–30U/d) vs PRD Cessation of 12– 0
(2mg/kg/d) for 2wks, then spasms and 33mo
tapered over 1wk for disappearance of
responders HS
Baram et al.6 USA RCT NA 29 2–21 12/17 IS with HS ACTH (150U/m2/d) vs PRD Cessation of 2– 0
(2mg/kg/d) for 2wks, then spasms and 48mo
tapered over 15d elimination of HS
by the end of the
2wk treatment
Lux et al.14 UK Multi-centre, RCT Jun 1999–Dec 55 4–9 32/23 IS with HS or PRDL (40–60mg/d) vs Cessation of 29d 0
2002 similar tetracosactide (40–60IU/ spasms for at least
alternated) for 2wks, then 48h including day
tapered over 15d 13; resolution of
HS on day 12–19
after treatment
Wanigasinghe Sri Lanka Single-blind, RCT 2010–2014 97 2–30 56/41 IS with HS Synthetic ACTH (40–60IU/ Remission of IS by 42d 6
et al.17 alternated) vs PRDL (40– end of day 14 and
60mg/d) for 2wks, then electroclinical
tapered over 3wks remission by end
of day 14; other
secondary
outcomes
O’Callaghan Five Multi-centre, RCT Mar 2007–May 377 2–14 210/ IS with HS or The protocol for hormone Freedom from 6wks 0
et al.15 countries 2014 167 similar treatment is the same as spasms on and
that in Lux et al.17 between day 14
and day 42 from
trial entry;
cessation of
spasms and
resolution of HS
EEG; other
secondary
outcomes
Wanigasinghe Sri Lanka Randomized, 2010–2014 97 2–24 56/41 IS with HS The same as that in The proportion of 12mo 22
et al.16 single-blind, Wanigasinghe et al.17 freedom from
parallel trial The same hormone spasms at 3, 6,
treatment was repeated and 12mo
and other anti-
convulsants were
introduced for relapsed
patients during follow-up
Gowda et al.12 India Single centre, RCT Oct 2013–Oct 34 2–60 21/13 IS (no detailed ACTH (100IU/body surface Cessation of 6mo 3
2015 EEG) area/d vs PRDL 4mg/kg/d spasms at day 14,
for 2wks, then tapered day 28
over 3–4wks)

RCT, randomized controlled trial; NA, not available; IS, infantile spasms; HS, hypsarrhythmia; ACTH, adrenocorticotropic hormone; U, unit; PRD, prednisone; PRDL, prednisolone;

Review
EEG, electroencephalogram.

577
outcome-blinded, and 3 out of 6 were allocation-concealed.
Figure S2 (online supporting information) shows a high
risk of bias of the included studies.
ACTH/tetracosactide versus prednisolone/prednisone
Cessation of spasms
Five RCTs with a total of 238 patients reported data on
cessation of spasms at day 14 after initial hormone treat-
ment,6,12–14,17 as did four studies with 531 participants on
and between days 14 and 42 as well as only one study with
97 patients at 3, 6, and 12 months.12,13,15–17
Compared with prednisolone/prednisone, ACTH/tetra-
cosactide was not superior in terms of cessation of spasms
at day 14 (relative risk 1.19, 95% CI 0.74–1.92; Fig. S3a,
online supporting information). As there was significant
heterogeneity in the included studies, the random-effects
model was used (I2=67%, p=0.02; Fig. S3a).
In line with the tendency at 2 weeks, no obvious differ-
ence was found between the two groups during the period
starting from day 14 to 6 weeks (relative risk 1.02, 95% CI
0.63–1.65; Fig. S3b). The random-effects model was used
owing to the presence of significant heterogeneity
(I2=57%, p=0.07; Fig. S3b).
Resolution of the hypsarrhythmia EEG pattern
Four studies involving 532 cases reported data on resolu-
tion of the hypsarrhythmia EEG pattern,6,14,15,17 resulting
in no considerable difference between the two groups (rela-
tive risk 1.14, 95% CI 0.71–1.81) using a random-effect
model (I2=79%, p=0.003) (Fig. S4, online supporting infor-
mation). Hrachovy et al. did not report the cases with res-
olution of hypsarrhythmia EEG pattern in the prednisone
group;13 therefore, it was not included in the calculation of
relative risk.
Adverse events
Among the six cohorts comparing the efficacy of ACTH/
tetracosactide and prednisolone/prednisone,6,12–15,17 three
studies with a total 343 participants presented detailed data
on adverse effects.14,15,17 Despite the apparently less fre-
quent incidences of side effects caused by ACTH/tetracos-
actide, the pooled data showed that the incidences of
ACTH/tetracosactide were not lower than that of pred-
nisolone/prednisone for irritability (relative risk 0.79, 95%
CI 0.57–1.10), increased appetite (relative risk 0.78, 95%
CI 0.57–1.08), weight gain (relative risk 0.86, 95% CI
0.56–1.32), and gastrointestinal upset (relative risk 0.60,
95% CI 0.35–1.02) (Fig. S5a–d respectively, online sup-
porting information). The fixed-effects model was used
(I2=0%, p=0.78; I2=0%, p=0.63; I2=0%, p=0.40; I2=0%,
p=0.37 respectively) (Fig. S5a–d).
In addition, approximate incidences of 10% were
reported for fluid and electrolyte adverse effects (hyperten-
sion-inclusive) and infection. Hrachovy et al. found that
62% of patients (10 out of 16) who received ACTH or
prednisone showed evidence of increased ventricular size
or increased subarachnoid space, or both, compared with
578 Developmental Medicine & Child Neurology 2020, 62: 575–580
baseline computed tomographies,13 whereas the other
included RCTs did not mention cerebral shrinkage. Pred-
nisolone had to be discontinued in one patient (2%, 1 out
of 48) owing to hypertension.18 Hormone treatment was
withdrawn for one child in each group (prednisolone: 3%,
1 out of 30; tetracosactide: 4%, 1 out of 25) without clear
cause.14
Sensitivity analyses and publication bias
The efficacy of different ACTH doses for treating infantile
spasms could be considered indistinguishable according to
the American Academy of Neurology recommendations.7
We therefore conducted subgroup analysis on the different
doses of prednisone/prednisolone and ACTH/tetracosac-
tide. Compared with ACTH, either low-dose (2mg/kg/d)
or high-dose prednisone/prednisolone demonstrated simi-
lar effects of spasm cessation at day 14 (relative risk 2.05,
95% CI 0.87–4.87; relative risk 0.94, 95% CI 0.60–1.50
respectively; Fig. S6a, online supporting information) and
during the time starting from day 14 until 6 weeks (relative
risk 1.25, 95% CI 0.44–3.55; relative risk 0.96, 95% CI
0.51–1.78 respectively; Fig. S6b). In one RCT,15 hormonal
treatment in 186 of 377 patients was combined with viga-
batrin, and the subgroup analysis shows that vigabatrin was
not the heterogeneity source of medication effect at the
end of the sixth week (Fig. S7, online supporting informa-
tion). There was no evidence of potential publication bias
(Egger’s test, p=0.276; Begg’s test, p=0.462; Fig. S8, online
supporting information).
DISCUSSION
Compared with the meta-analysis published in 2013,19 the
present study includes four additional RCTs published
since then.12,15–17 The present meta-analysis of six RCTs
found that oral corticosteroids are as effective as ACTH in
terms of cessation of spasms and resolution of hypsarrhyth-
mia on EEG in infantile spasms.6,12–15,17 Interestingly, cor-
ticosteroids were associated with a decreased spasm
compared with ACTH at 3, 6, or 12 months.16 Moreover,
there was no significant difference in the clinical responses
in the subgroup for different corticosteroid doses. On the
basis of the high cost and limited accessibility of ACTH,
prednisolone or prednisone may be an effective alternative
for ACTH, which justifies the recommendations by 2017
Quality Measure Set from the American Academy of Neu-
rology and Child Neurology Society and Rag et al.8,10
On the basis of the evidence suggesting that low-dose
ACTH is probably as effective as high-dose ACTH for
short-term treatment of infantile spasms,7 we disregarded
dose dependence when referring to the effectiveness of
ACTH and focused only on the different corticosteroid
doses. In the subgroup analysis, corticosteroids with any
high (40–60mg/d or 4mg/kg/d) or low (2mg/kg/d) dose
exerted similar antiepileptic effects as ACTH. However,
only two small, detailed RCTs (24 cases13 in 1983 and 29
cases6 in 1996 respectively) compared the difference in
effectiveness between low-dose prednisone and ACTH,
and the small sample size may have decreased the informa-
tive value of the conclusions themselves. Baram et al., ref-
erenced in most meta-analyses on therapeutic outcomes,
used a very high dose of ACTH (150U/m2/d) compared
with a low prednisone dose (2mg/kg/d), which resulted in
the superiority of ACTH over prednisone.6 The great
imbalance in the doses may have biased the study outcome.
Moreover, the involvement of patients with tuberous scle-
rosis in their cohort may also have confounded the differ-
ence in efficacy between ACTH and prednisone, as
vigabatrin is considered one of the first-line therapies for
tuberous sclerosis-related seizures.20 Although one trial
demonstrated no difference between corticosteroids and
ACTH,13 we cautiously conclude that low-dose corticos-
teroid has similar responses to ACTH. This was because
antiepileptic drug treatment before the introduction of
ACTH or corticosteroids may have biased the result in 15
cases (24 cases in total), which was also implied by the
lower percentage (42%, 5 out of 12) of electroclinical
remission of ACTH with 20U/day to 30U/day compared
with other RCTs.13,14,17 Since Hancock et al. first reported
that high-dose prednisolone (60mg/d) resulted in spasm
cessation in 71% of patients (10 out of 14),21 an increasing
number of trials with high-dose corticosteroids have been
conducted which have concluded that high-dose corticos-
teroids have similar effects on spasm abolition as ACTH.
In the present study, five RCTs involving 660 cases investi-
gated the effectiveness of ACTH and high-dose pred-
nisolone,12,14–17 which resulted in the highly consistent
conclusion that high-dose corticosteroids were not inferior
to ACTH in the cessation of spasms. Moreover, the study
of Chellamuthu et al. showed that high-dose prednisolone
(4mg/kg/d) was more beneficial than the low dose in the
cessation of spasms (51.6% vs 25%), which corroborated
the superior effect of high-dose corticosteroids.22 This
clinical response is in line with the findings of observa-
tional or retrospective studies.21,23–26 For the long-term
aspects, Wanigasinghe et al. found that 40mg/day to
60mg/day prednisolone resulted in even better control of
spasms at 3 months compared with ACTH, whereas there
was no significant difference in the control of spasms at 6
and 12 months between the two medications.16 Also,
O’Callaghan et al. recently published data on developmen-
tal and epilepsy outcomes at 18 months of age in patients
with infantile spasms treated with the same regimen as that
previously described,15 and found no significance between
40mg/day to 60mg/day doses of prednisolone and
ACTH.27 Nevertheless, considering the hypothesis on the
pathophysiology of infantile spasms, which states that
hypothalamic release of corticotropin-releasing hormone
(an excitatory cotransmitter) leads to seizures in the devel-
oping brain,28 it is postulated that high-dose corticos-
teroids exert stronger anti-seizure effects because the
higher concentration of glucocorticoids could inhibit corti-
cotropin-releasing hormone secretion more strongly by
long-loop feedback. Thus, high-dose prednisone/pred-
nisolone might be superior over low dose for achieving
freedom from spasms. Meanwhile, well-designed trials with
large samples and long-term follow-up are urgently needed
to elucidate the relative potency of ACTH versus corticos-
teroid.
The pooled analysis of three studies involving a total
of 343 participants also resulted in similar adverse effects
manifestation and incidence, irrespective of the hormone
category.14,15,17 The most common adverse events were
irritability and increased appetite. These data all suggest
that the adverse effects of ACTH and corticosteroids, even
high-dose prednisone/prednisolone, are tolerable.
Regarding treatment duration, all the RCTs adopted a
2-week course of full dose of hormone, followed by effi-
cacy assessment.6,12–17 This high consistency may have
been due to the well-acknowledged fact that response to
hormone therapy is all or none—that is, complete control
or no control29,30—as well as the potentially deleterious
effects of these agents over time. Accordingly, on the basis
of the clinical aspects, ACTH and corticosteroid pharma-
cokinetics, and presumed pathophysiology, a 2-week course
of full dose hormone treatment is reasonable and sufficient
for hormone-responsive participants.
The data on the efficacy of corticosteroids compared
with ACTH are promising and encouraging. However,
because of the limitations of large aetiological heterogene-
ity, marked variation in the inclusion criteria, drop-outs,
treatment lag, definition of response, proportion of low/
high risk, symptomatic patients, therapy dose and duration,
and length of follow-up, the data are not sufficient to draw
confident evidence-based conclusions on the comparative
effectiveness of ACTH and corticosteroids.
Limitations
First, the RCTs included in this study were conducted
under different study sets and baseline characteristics of
the cases were variable, all of which could have resulted in
the heterogeneity. Second, methodological quality was low
or unclear in most of the eligible studies. Third, most of
the eligible trials had small sample sizes, and few of them
reported more outcomes other than the short-term results.
Then, on account of the limited availability of data, rele-
vant adverse effects associated with treatment could not be
fully evaluated. Lastly, owing to the relative paucity of
cases with low-dose prednisone (only 53 cases in two
RCTs studies totally),6,13 we should be cautious about
drawing any conclusion on the superiority between ACTH
and low-dose prednisone.
CONCLUSIONS
The present meta-analysis demonstrates that oral corticos-
teroids are as effective as ACTH for electroclinical remis-
sion and the adverse events resulting from both
medications are similar and tolerable. High-dose pred-
nisolone might be superior to low-dose prednisolone for
achieving freedom from spasms, and favours the same
long-term remission of seizures as ACTH. Therefore, on
the basis of the current evidence, it is reasonable to
Review 579
conclude that high-dose prednisone/prednisolone has Figure S2: Assessment of bias risk.
already evolved as an alternative candidate for infants with Figure S3: Forest plot of effect of ACTH versus prednisone/
epileptic spasms, especially in settings with limited accessi- prednisolone on cessation of spasms.
bility to ACTH. Figure S4: Forest plot of effect of ACTH versus prednisone/
prednisolone on resolution of the hypsarrhythmia EEG pat-
A CK N O W L E D G E M E N T tern.
We thank Liping Tan for comments on the manuscript. The Figure S5: Forest plot of effect of ACTH versus prednisone/
authors have stated that they had no interests that might be per- prednisolone on adverse events.
ceived as posing a conflict or bias. Figure S6: Forest plot of subgroup analysis of ACTH versus
different doses of prednisone/prednisolone.
SUPPORTING INFORMATION Figure S7: Subgroup analysis with combined vigabatrin or not
The following additional material may be found online: on cessation of spasms at the end of 6 weeks.
Figure S1: RCT selection process. Figure S8: Egger’s publication bias.

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580 Developmental Medicine & Child Neurology 2020, 62: 575–580

 DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY SYSTEMATIC REVIEW

RESUMEN

pica para los espasmos infantiles: un metana
Prednisolona/prednisona como alternativa a la hormona adrenocorticotro
lisis de
ensayos controlados aleatorios
OBJETIVO

pica (ACTH) en el tratamiento de
Comparar la eficacia y seguridad de la prednisolona/prednisona y la hormona adrenocorticotro
los espasmos infantiles mediante un metana
lisis de ensayos controlados aleatorios (ECA).
M

ETODO
En una bu
squeda sistema
tica en la literatura de bases de datos electro

nicas (MEDLINE, Embase, Cochrane Library), identificamos
ECA que evaluaban prednisolona/ prednisona en comparacio
n con ACTH/tetracosactida en pacientes con espasmos infantiles. Se
evaluaron la respuesta electro cl
ınica y los eventos adversos.
RESULTADOS
Seis ECA (616 participantes) se incluyeron en el metana
lisis. En comparacio
n con la prednisolona/prednisona, la ACTH/tetracosac-
tida no fue superior en te
rminos de cese de espasmos en el d
ıa 14 (riesgo relativo 1,19, intervalo de confianza del 95% [IC] 0,74–

n de la hipsarritmia en el EEG (riesgo relativo 1,14, IC 95%
1,92), d
ıa 42 (riesgo relativo 1,02, IC del 95% 0,63– 1,65), y la resolucio
0,71–1,81); la incidencia de reacciones adversas comunes causadas por ACTH/tetracosactida no fue inferior a la de predniso-
lona/prednisona para irritabilidad (riesgo relativo 0,79, IC 95% 0,57-11,10), aumento del apetito (riesgo relativo 0,78, IC 95% 0,57-
1,08), aumento de peso (riesgo relativo 0,86; IC del 95%: 0,56–1,32) y malestar gastrointestinal (riesgo relativo 0,60; IC del 95%:
0,35–1,02), aunque parec
ıa menos frecuente.


INTERPRETACION
La prednisolona/prednisona provoca una respuesta electro cl
ınica similar a la ACTH para los espasmos infantiles, lo que indica
que puede ser una alternativa a la ACTH para el tratamiento de los espasmos infantiles.

RESUMO
^ nio adrenocorticotro
Prednisolona/predinisona como hormo
pico alternativo para espasmos infantis: uma metana

lise de estudos
randomizados controlados
OBJETIVO
Comparar a efica
cia e segurancßa da prednisolona/ prednisona e hormo
^ nio adrenocorticotro

pio (HACT) no tratamento de espasmos
infantis usando uma metana
lise de estudos randomizados controlados (ERCs).
M

ETODO
Em uma busca sistema
tica da literatura em bases de dados eletro
^ nicas (MEDLINE, Embase, Biblioteca Cochrane), identificamos
ERCs que avaliaram a prednisolona/ prednisona em comparacßa ~o com o HACT/ tetracosact
ıdeo em pacientes com espasmos infan-
tis. A resposta eletrocl
ınica e eventos adversos foram avaliados.
RESULTADOS
Seis ERCs (616 participantes) foram inclu
ıdos na metana
lise. Comparado com a prednisolona/ prednisona , o HACT/ tetraco-
sact
ıdeo na~ o foi superior em termos de cessacßa ~o dos espasmos no dia 14 (risco relativo 1,19, intervalo de confiancßa [IC] a 95%
~o da hipsarritimia no EEG (risco relativo 1,14, IC 95% 0,71–1,81);
0,74–1,92), dia 42 (risco relativo 1,02, IC 95% 0,63–1,65), e resolucßa
as incide ~ es adversas comuns causadas pelo HACT/ tetracosact
ıdeo na
^ ncias de reacßo ~ o foram menores que as da prednisolona/
prednisona para irritabilidade (risco relativo 0,79, IC 95% 0,57–1010), aumento do apetite (risco relativo 0,78, IC 95% 0,57–1,08),
ganho de peso (risco relativo 0,86, IC 95% 0,56–1,32), e mal-estar gastrointestinal (risco relativo 0,60, IC 95% 0,35–1,02), embora
parecessem menos frequentes.
~
ß AO
INTERPRETAC
A prednisolona/ prednisona /prednisone elicia resposta eletrocl
ınica similar ao HACT para espasmos infantis, o que indica que
pode ser uma alternativa ao HACD para tratar espasmos infantis.