REVIEW
Pediatrics Sciences Journal (PedSci.
Volume 4.
Number 2: 36-44 P-ISSN: 2722-0427.
E-ISSN: 2722-1474
Efficacy of ketogenic diet therapy in infants with epilepsy: A systematic review and meta-analysis Published by Pediatrics Sciences Journal Nadzila Anindya Tejaputri1*.
Salsabiila Maryam1.
Dina Clarisa1.
Putri Amelia1
ABSTRACT
Faculty of Medicine.
Universitas Indonesia.
*Corresponding to:
Nadzila Anindya Tejaputri.
Faculty of Medicine.
Universitas Indonesia.
anindyanadzila@gmail.
Received: 2022-09-08 Accepted: 2023-11-05 Published: 2023-12-01 Introduction: The ketogenic diet therapy, a high-fat, low-carbohydrate diet, has been known since the 1920s as a therapeutic option in treating drug-resistant epilepsy.
However, with the increasing incidence of the infant population, research on this subject is still limited.
This systematic review and meta-analysis aimed to evaluate the efficacy of ketogenic diet therapy in infants with epilepsy.
Methods: We searched the articles from Cochrane Library.
Embase.
Pubmed.
ScienceDirect, and Scopus, based on predetermined inclusion criteria.
Four investigators independently performed screening, study selection, extracted data, and assessed the quality of relevant articles.
We used the Newcastle-Ottawa Quality Assessment Scale to assess the risk of bias in included articles.
We present the results of the meta-analysis using a forest plot.
Results: We identified 1781 studies from database screening, with eight cohort studies in this study.
Our meta-analysis revealed that an estimate of 69% of infants with epilepsy achieved Ou50% seizure reduction in three months follow-up .
% confidence interval [CI] 56- 82%) and an estimate of 36% of infants achieved seizure freedom .
% confidence interval [CI] 20- 51%).
Retention rates ranged from 91% at three months to 28% at 24 months.
The most common side effects reported were dyslipidemia .
/355, 36.
9%), gastrointestinal disturbances .
/355, 18.
6%), and hyperkeratosis/acidosis .
/355, 8%).
Conclusion: Ketogenic diet therapy is well tolerated and effectively reduces seizure frequency at three months in infants with epilepsy.
Keywords: epilepsy, infants, ketogenic diet therapy.
Cite This Article: Tejaputri.
Maryam.
Clarisa.
Amelia.
Efficacy of ketogenic diet therapy in infants with epilepsy: A systematic review and meta-analysis.
Pediatrics Sciences Journal 4.
: 36-44.
DOI: 10.
51559/pedscij.
INTRODUCTION
Epilepsy is one of the most common diagnoses encountered by pediatric Identifying the type of epilepsy syndrome through EEG results and the clinical picture is essential to determine the etiology, management, and 1,2 The incidence of epilepsy in children varies quite widely in Western countries compared to developing countries, namely around 33.
3-82/100,000
cases per year in Western countries and around 187/100,000 cases per year in developing countries, with the highest incidence rate at the first year of life, is 102/100,000 cases per year.
Most children with epilepsy respond to treatment and are free of seizures.
However, some children do not respond treatments, developing drug-resistant According to the International League Against Epilepsy (ILAE), drugresistant epilepsy is Aofailure of adequate trials of two antiepileptic drugs (AED.
that are tolerated, properly selected and usedAo.
The prevalence of children with drug-resistant epilepsy is estimated at One that has been widely studied as a treatment option for DRE in children is ketogenic diet therapy (KDT).
The ketogenic diet therapy is a high-fat, low-carbohydrate diet designed to mimic the fasting state.
The use of KDT has grown since 1911, but its use has decreased since the emergence of various antiepileptic In the modern era.
KDT began to develop again in 1994, where the story of a boy named Charlie with DRE was able to control his seizures using KDT.
6 Various RCTs have also proven the effectiveness and safety of KDT in treating DRE.
7,8,9
However, data regarding the use of KDT in infants under two years of age is still This systematic review and metaanalysis aimed to evaluate the efficacy of ketogenic diet therapy in infants with Our meta-analysis focused on the efficacy of KDT in infants with epilepsy, but we also reviewed the safety of KDT in this particular population group.
METHODS
We conducted a systematic review and meta-analysis based on PRISMA Several databases, including Cochrane Library.
Embase.
PubMed.
ScienceDirect, and Scopus, were searched with the following keywords, summarized in Table 1.
The search included data up until April 27, 2023.
Inclusion Criteria.
Study selection, and Data extraction We included RCTs and observational cohort studies that fulfilled the inclusion criteria: full-text articles published online in English from 2013 onwards, at least one participant in the study age 0-24 months or was stated as AuinfantAy.
If the study included participants of varying ages, they should clearly separate and specify the data for each age group, and the KDT should last Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 4.
36-44 | 10.
51559/pedscij.
Open access:
https://pedscij.
id/index.
php/pedscij REVIEW Table 1.
Database search strategy keywords Database Cochrane Library Embase PubMed ScienceDirect Scopus Search keywords .
AND .
AND .
etogenic die.
AND .
eizure frequenc.
(AoinfantAo/exp OR infan.
AND (AoepilepsyAo/exp OR epileps.
AND (Aoketogenic dietAo/exp OR Aoketogenic dietAo OR .
etogenic AND (AodietAo/exp OR die.
)) AND (Aoseizure frequencyAo/exp OR Aoseizure frequencyAo OR ((AoseizureAo/exp OR seizur.
AND (AofrequencyAo/exp OR frequenc.
)) .
AND .
AND .
etogenic die.
AND .
eizure frequenc.
AND .
AND .
etogenic die.
AND .
eizure frequenc.
TITLE-ABS-KEY ( infant ) AND ( epilepsy ) AND ( ketogenic diet ) AND ( seizure frequency ) .
rates of retention in the study.
adverse side effects experienced by infants.
Figure 1.
PRISMA flowchart on the literature search and screening process.
for a minimum of one month.
All types of KDT were included without exception.
removed duplicates from the first results on all the databases.
Four investigators independently screened the titles and abstracts to assess article eligibility based on predetermined inclusion criteria.
Disagreements were resolved through deliberation.
The relevant data were collected using a comprehensive data extraction form including the following information: .
first authorAos .
study and publication year.
design of the study.
population involved in the study.
clinical setting of the study.
type of epilepsy/seizure.
number of infants who initiated the diet.
type of ketogenic diet used.
seizure outcomes at 1, 3, 6, 12, and 24 months.
seizure outcomes at other unspecified time Quality Appraisal We used the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies to assess the risk of bias in included This checklist comprises three domains of questions based on selection, comparability, and outcome.
The selection domain consists of four questions:
representativeness of the exposed cohort, selection of the non-exposed cohort, ascertainment of exposure, and demonstration that the outcome of interest was not present at the start of the study.
The comparability domain consists of one question whether the cohort is comparable based on the design or analysis.
This domain of question allows for a maximum allocation of two stars.
The outcome domain consists of three questions: the outcome assessment, whether the followup was long enough for outcomes to occur, and the adequacy of the follow-up of cohorts.
Based on AHRQ standards, the Newcastle-Ottawa scales can be converted to good quality if there are 3-4 stars in the selection domain and 1-2 stars in the comparability domain, and 2-3 stars in the outcome domain.
The article has fair quality if there are 2 stars in the selection domain, 1-2 stars in the comparability domain, and 2-3 stars in the outcome Poor quality is considered if there is only 0-1 star in the selection domain or 0 stars in the comparability domain, or 0-1 star in the outcome domain.
Outcomes The primary outcome of this study was the efficacy of KDT for epilepsy in infants aged 0-24 months.
The efficacy was measured by determining the number or percentage of infants who achieved a seizure reduction Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
REVIEW
of 50% or more after a follow-up period of at least one month.
The secondary outcomes were seizure freedom rates within one month of follow-up onwards, retention rates, and side effects.
Data Analysis Our statistical analysis was carried out using OpenMetaAnalyst.
Heterogeneity was assessed through the evaluation process by MantelAeHaenszel N 2 test and the I 2 statistic.
A fixed-effects model was utilized if the I2 value was below 50%, indicating acceptable heterogeneity.
the other hand, if the I2 value exceeded 50% .
ndicating high heterogeneit.
, a random-effects model was employed.
The statistical significance of the results was determined by a p-value below 0.
RESULTS
We identified 1781 studies by screening five databases.
Out of these, 1047 studies were removed: 263 were duplicates, 400 were not listed as academic journals, and 384 were review articles or conference We then screened and assessed compatibility with PICO for 734 studies.
Among them, only 20 studies remained for retrieval, while two studies were excluded because full texts were not Finally, 18 studies were assessed for eligibility, of which eight studies met our inclusion criteria.
(Figure .
Study Characteristics Out of the eight studies included in this review involving 366 infants, five were cohort retrospective studies, and three were cohort prospective studies.
Table 1 presents the summary descriptive data of the studies included.
Most studies involved infants with various epilepsy syndromes, with only one specifically focusing on infants with infantile spasms.
Three out of the eight studies specifically included infants with refractory epilepsy.
From six studies, 56% of the infants were male .
, and the mean age at which they started the ketogenic diet was 8.
64 months, as reported by all eight studies.
The types of ketogenic diets used varied among the studies, including the classic ketogenic diet .
ith ratios of 4:1, 3.
5:1, 3:1, 2.
5:1,
and modified ketogenic diets such as the modified Atkins diet (MAD), and medium chain triglyceride diet (MCT).
Information on the proportion of ketogenic diets used was provided in five studies, which revealed that 86% of the infants .
used the classic ketogenic diet, with a majority of them following a 3:1 ratio .
8%).
Additionally, 13% of the infants .
used MAD, while only 0.
7% .
used MCT.
Study Quality The risk of bias was assessed from available full text using Newcastle-Ottawa Quality Assessment Form for Cohort studies.
The elements are given in Figure 2.
All included studies were rated as AugoodAy Only one study describes the nonexposed cohort selection from the same community as the exposed cohort.
Efficacy of Ketogenic Diet Therapy Data were available from 8 studies involving a total of 366 infants.
The total number of infants analyzed varied because efficacy rates were not presented at the same time point in each study.
After one month, 56 out of 89 infants .
%) achieved Ou50% seizure reduction .
ange 29%-83%.
median 72%.
IQR 20%),
and 11 out of 42 infants .
%) achieved seizure-free status .
ange 20%-35%.
median 28%.
IQR 8%).
After three months, 239 out of 335 infants .
%) achieved Ou50% seizure reduction .
ange 29%-88%.
median 67%.
IQR 19%), and 118 out of 288 infants .
%) achieved seizure-free status .
ange 20%-65%.
median 40%.
IQR 24%).
After six months, 192 out of 251 infants .
%) achieved Ou50% seizure reduction .
ange 0%-94%.
median 79%.
IQR 21%),
and 102 out of 251 infants .
%) achieved seizure-free status .
ange 19%-60%.
median 35%.
IQR 22%).
After 12 months, 166 out of 212 infants .
%) achieved Ou50% seizure reduction .
ange 41%-100%.
median 89%.
IQR
12%), and 95 out of 189 infants .
%) achieved seizure-free status .
ange 18A%.
median 33%.
IQR 35%).
After 24 months, out of 35, 27 infants .
%) achieved Ou50% seizure reduction .
ange 67%-100%.
median 86%.
IQR 17%),
and ten infants .
%) achieved seizurefree status .
ange 19%-57%.
median 29%.
IQR 19%).
One study that presented efficacy rates at an unspecified time point reported that 2 out of 24 .
%) achieved seizure-free Meta-analysis From the analysis of eight studies, the pooled response proportion for infants who achieved Ou50% seizure reduction at three months or an unspecified time 69 .
% CI 0.
, with high heterogeneity (I2=87.
19%, p <0.
Due to high heterogeneity, a binary randomeffects model was applied.
These results indicate that approximately 69% of infants treated with ketogenic diet therapy will experience Ou50% seizure reduction at three months or an unspecified time.
Based on the analysis of seven studies, the pooled response proportion from these studies was 0.
% CI 0.
and there was a high level of heterogeneity (I2=89.
39%, p <0.
A binary randomeffects model was used to account for this These findings suggest a significant percentage .
%) of infants can experience relief from seizures by implementing ketogenic diet therapy at three months or an unspecified time.
Retention Rates The minimum duration of treatment with the ketogenic diet was one month, and the longest was 60 months.
Seven studies were included for calculating the retention rate of KD at months 3, 6, 12, and 24.
The retention rates were 253 out of 279 .
%) at three months, 226 out of 308 .
%) at six months, 154 out of 262 .
%) at 12 months, and 35 out of 124 .
%) at 24 months.
All individuals in the included studies were receiving a classical KD, except for n = 2 on a KD-MCT (Ketogenic Diet with Medium-Chain Triglyceride.
with unknown duration, n = 34 on a MAD (Modified Atkins Die.
with unknown duration, and four individuals switched diet therapy from KD or MCT to MAD.
Reasons for diet discontinuation were given below .
e calculated the percentages using the total number of individuals whose reasons for diet discontinuation were reported in each stud.
Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
Cohort Cohort Cohort Study Pires ME et Dressler A et al 201512 Ismayilova N et al Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
All infants (<2 years ol.
with medicationrefractory epilepsy were treated with KD at the Evelina London ChildrenAos Hospital between 2006 and 2016.
115 children with epilepsy treated with KD at the Medical University Vienna from March 1999-April 2014 .
ivided into group A (<1,5 years, n=.
and group B (>1,5 years, n=.
17 patients with IS refractory to vigabatrin (VGB) and hydrocortisone (HC) Study population Infantile spasms, n=59 LennoxAeGastaut syndrome, n=20 Dravet syndrome, n=10 Partial epilepsy, n=10 Idiopathic epilepsy, n=6 Progressive epilepsy, n=3 Myoclonic astatic epilepsy, n=2 Ohtahara syndrome, n=2 CSWS, n=2 Pseudo-Lennox syndrome, n=1 Symptomatic epilepsy, n= 15 Idiopathic epilepsy, n=14 Medical Evelina London ChildrenAos Hospital Symptomatic infantile spasms, n= 9 Cryptogenic infantile spasms, n= 8 Epilepsy/ seizure type RobertDebry Hospital.
Paris & University Hospital.
Amiens Clinical Summary descriptive data of the studies included Design Table 2.
5 weeks- 23 58 .
ean age 68 A 0.
45 year.
Number of starting the diet .
ge rang.
ean age 9.
A 1.
1 month.
Classic 3:1 ketogenic diet .
and MCT .
Classic ketogenic diet 4:1, 3:1, 3.
5:1,
5:1, and 2:1 Classic ketogenic diet 4:1 or 3:1 ratio Ketogenic diet type 7 .
>50% seizure 3 .
<50% seizure 3 .
%) <50% seizure 19 .
seizure free 20 .
seizure free 9 .
seizure free 11 .
seizure free 32 .
>50% seizure 14 .
Ou50% seizure 15 .
Ou50% seizure 37 .
>50% seizure 2 .
<50% seizure Seizure outcome .
, n (%) 2 .
<50% seizure Seizure outcome .
, n (%) .
>50%
Seizure .
, n (%) time point:
seizure free 1 mo:
>50%
seizure free >12 mo:
9/18 .
seizure free 13 .
Ou50% Seizure .
, n (%) 1 mo:
<50%
on diet at 6 mo 24 .
%) on diet at 1 mo 16 .
on diet at 6 mo 17 .
%) on diet at 3 mo Retention, n(%) REVIEW Cohort Cohort Wirrell E et Riantarini I et al 201915 Design Study 115 infants with epilepsy treated with a ketogenic diet or Modified Atkins Diet (MAD) from January 1, 2006, to June 30, 2016, at Severance Children Hospital.
South Korea All infants less than 12 months of age with epilepsy and treated with a ketogenic diet at Mayo Clinic.
Rochester, between September 1, 2007, and July 31, 2016.
Study population Severance Children Hospital.
South Korea Mayo Clinic Rochester.
Clinical Infantile spasms, n= 92 Infantile epileptic n= 13 Early myoclonic n= 1 Migrating focal seizures in infancy, n= 2 Severe myoclonic epilepsy in infancy, n=3 Unclassified epilepsy, n=1 Unclassified focal epilepsy, n=3 Focal spasm, n=18 Epileptic spasm, n=13 Epilepsy/ seizure type 115 .
7 month.
Number of starting the diet .
ge rang.
edian age 7 ange 511 month.
) Classic
diet 3:1 ratio
%)),
Modified Atkins Diet
(MAD)
%)),
and classic ketogenic diet 4:1 ratio .
%)).
Classic ketogenic diet 2:1 ratio .
Ketogenic diet type 5 .
<50% seizure 15 .
50-89% seizure 14 .
7%) Ou 90% seizure 50 .
seizure free 29 .
50-89% seizure 5 .
8%) Ou 90% seizure 58 .
seizure free 5 .
seizure free 9 .
%) seizure 12 .
<50% seizure 14 .
Ou50% seizure Seizure outcome .
, n (%) 16 .
%) Ou50% seizure Seizure outcome .
, n (%) .
Ou 90% 7 .
%) 50-89% 4 .
<50%
Seizure .
, n (%) 10 .
%) Ou50% 2 .
seizure free 24 mo:
Ou50% 5 .
%) seizure free Seizure .
, n (%) 1 mo:
Ou50% 70 .
on diet at 12 mo 84 .
%) on diet at 6 mo 7 .
%) on diet at 24 mo 104 .
on diet at 3 mo 11 .
on diet at 12 mo 17 .
4/%)
on diet at 6 mo 20 .
%) on diet at 3 mo 25 .
on a diet at 1 mo Retention, n(%) REVIEW Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
Design Cohort Cohort Cohort Study Armeno M et al 202116 Liu Y et al.
RuizHerrero J et All the infants with epilepsy on a KDT at the Niyo Jesys Pediatric Hospital of Madrid (Spai.
between January 2000 and December Children with refractory epilepsy .
ivided into the A .
-12 m.
B .
-24 m.
C .
-36 m.
Infants < 2 years with drugresistant epilepsy treated with CKD at Hospital de Pediatrya Garrahan between February 2013 and September 2020 Study population Niyo Jesys Pediatric Hospital of Madrid Tonic seizure, n= 33,3% Focal onset seizure, n= 26,2% Various types, n=14,3% Generalized tonic-clonic seizure, n=4 Myoclonic seizure, n=3 Clonic seizure.
West syndrome, n=30 Migrating focal seizures, n=7 Dravet syndrome, n=4 Ohtahara syndrome, n=2 Myoclonic epilepsy, n=1 Infantile spasms without Hospital de Pediatria Garrahan.
Buenos Aires.
Argentina ChildrenAos Hospital of Chongqing Medical University Epilepsy/ seizure type Clinical 42 .
5- 16.
group A .
ean age 00A3.
and 14 group B .
ean 6A3.
Number of starting the diet .
ge rang.
Classic ketogenic diet ratio 3:1 .
, ratio 4:1 .
, and modified diet with medium-chain .
Classic ketogenic diet :1- 4:.
Classic diet 4:1 ratio of 4 .
1%),
3:1 ratio of 30 .
6%),
5:1 ratio of 7 .
5%), 2:1
ratio of 14 .
%), and 1:1 ratio of 1 .
Ketogenic diet type 13 .
Ou90% seizure 9 .
seizure free 14 .
Ou90% seizure 9 .
seizure free 3 .
%) 9099% seizure 3 .
%) 9099% seizure 19 .
Ou50% seizure 15 .
50-90% seizure 13 .
50-90% seizure 21 .
Ou50% seizure 5 .
<50% seizure 10 .
seizure free 11 .
seizure free 7 .
<50% seizure 34 .
>50% seizure Seizure outcome .
, n (%) 35 .
>50% seizure Seizure outcome .
, n (%) Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
seizure free 5 .
Ou90% 4 .
90-99%
24 mo:
Ou50% 4 .
90-99%
Ou50% .
Ou90% 15 .
50-90%
50-90%
1 mo:
<50%
seizure free 6 .
<50%
Seizure .
, n (%) 24 mo:
>50%
Seizure .
, n (%) .
>50%
on diet at 24 mo 16 .
%) on diet at 12 mo 24 .
on diet at 6 mo 33 .
on diet at 3 mo 21 .
on diet at 24 mo 23 .
%) on diet at 3 mo, 6 mo, 12 mo 34 .
on diet at 12 mo 52 .
on diet at 6 mo 56 .
%) on diet at 3 mo Retention, n(%) REVIEW
REVIEW
DISCUSSION
Figure 2.
Assessment of risk of bias on included studies using Newcastle-Ottawa Quality Assessment Form.
Figure 3.
Forrest plot of Ou50% seizure reduction with ketogenic diet therapy in infants with epilepsy.
Figure 4.
Forrest plot of seizure-free with ketogenic diet therapy in infants with Non-compliance, n = 12/29 .
%) Ineffectiveness, n = 41/87 .
%) Adverse effects, n = 20/81 .
%): n = 5 GI disturbances.
n = 2 AuacidosisAy.
n = 2 Aupoor tolerabilityAy.
n = 2 Audehydration and acidosisAy, n = 1 Aumarkedly elevated triglyceride levelAy.
n = 1 Auhypercalciuria and bone fractureAy.
1 hypertransaminasemia Severe infections, n=8/22 .
%) Seizure-free, n = 9/40 .
%) Death due to causes unrelated to diet, n = 17/87 .
%) Poor oral intake, n=3/22 .
%) Adverse Side Effects The adverse side effects were assessed in five studies, which included a total of 355 infants.
The most frequently reported adverse side effects were .
/355, 9%), gastrointestinal disturbances .
/355, 6%), hyperketosis/acidosis .
/355, 8%), hypercalciuria .
/355, 10.
1%),
/355, 10.
1%), and nutritional deficiency .
/355, 9.
3%).
In this meta-analysis, we investigated the efficacy of ketogenic diet therapy (KDT) in reducing seizure frequency in infants with Our findings indicate that KDT can be an effective treatment for reducing seizure frequency in infants with epilepsy.
Approximately 69% of infants achieved a 50% or greater reduction in seizures after three months of receiving KDT, and 36% became seizure-free.
These findings are consistent with a previous systematic review from Lyons et that reported similar response rates in infants with epilepsy who received KDT.
The review found that 59% of participants experienced a 50% or greater reduction in seizures, and 33% became seizure-free within three months of starting KDT.
These response rates appear comparable to those observed in older children and adolescents.
A systematic review of uncontrolled studies from Lefevre et investigating the efficacy of KDT in children and adolescents with refractory epilepsy showed that 56% of participants experienced a 50% or greater reduction in seizures, with 16% becoming seizurefree.
20 Another review by Sourbron et al.
investigated the efficacy and tolerability of KD and MAD in children and adolescents with refractory epilepsy.
The participants were divided into two groups, an intervention group and a control group.
The review reported that 35-56.
1% of participants in the intervention group, receiving KDT or modified Atkins diet (MAD), achieved a 50% or greater seizure reduction compared to 6-18.
2% in the control group.
The efficacy of KDT was statistically significant compared to the control group: RR = 5.
% CI 3.
p < 0.
Interestingly, higher response rates were observed in infants compared to older children, which may be attributed to better compliance in younger children.
Riantarini et al.
showed that Infants may have a higher level of dietary compliance due to simpler meal plans and greater control exerted by parents.
15 The mean age of infants starting KDT in our review was 64 months, and it has shown a significant efficacy .
%) in reducing seizure These results are supported by the findings of Ismayilova et al.
13, which Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
REVIEW
Table 3.
Reported adverse effects in infants after receiving ketogenic diet therapy Adverse side effect GI disturbances .
omiting, diarrhea.
Nutritional deficiency .
inc, selenium, vit e, vit A, vit D, vit B12, carnitin.
Hyperketosis/ acidosis Hypertriglyceridemia/ hypercholesterolemia Hypocalcemia Food refusal/ poor oral intake Nephrocalcinosis/lithiasis Hypercalciuria Low T3/TSH Hematological GERD Hypoglycemia Weight gain Growth deficit/ weight loss Infection Dehydration Lipoid pneumonia Hepatitis/ increased liver enzyme Pancreatitis GI bleeding Chorea/dystonia Allergic reaction/rash Metabolic encephalopathy Hyperuricemia Anorexia indicated a tendency for a better response to KDT in infants younger than 12 months .
%) compared to those older than 12 months .
%).
Retention rates in infants receiving KDT in our review were similar to those reported in randomized controlled trials (RCT.
involving infants and older Retention rates ranged from 74% to 90% at 3-4 months, 66% at six months, and 58% at 16 months.
Martin-McGill et presented that retention rates tended to be higher in children under two years old, likely due to parental control and management of their diet.
The most common adverse effects reported in our review were dyslipidemia including vomiting, diarrhea, and Dyslipidemia was observed 9% of infants, which was higher than findings from other systematic Cai et al.
conducted a study on the safety and tolerability of the ketogenic Armeno et .
Dressler et .
Riantarini I et al15 .
Ruiz-Herrero J et al18 .
Wirrell et al14 Total .
= 355 (%)) 66 .
diet for treating refractory childhood In their research, hyperlipidemia occurred in 12.
8% of older children.
The most common adverse effect in older children was gastrointestinal disturbances, accounting for 40.
6% of all cases.
22 In our review, gastrointestinal disturbances occurred in 18,6% of infants, lower than in older children.
Similar to studies on older children, these adverse effects rarely led to diet discontinuation.
Most of them were well tolerated and manageable with medications or dietary adjustments.
However, the specific time these adverse effects began was not reported.
The timing of adverse effects associated with ketogenic diet therapy (KDT) is an important aspect that should be reported in future Understanding the timing of side effects can help healthcare professionals anticipate and manage potential adverse events more effectively.
By including data on the timing of side effects in studies on KDT, healthcare professionals can 42 .
gain insights into when specific adverse effects may occur during treatment.
This information can be valuable in clinical practice, allowing healthcare providers to inform patients and their families about potential side effects and provide appropriate support and intervention when needed.
This review has several limitations.
All included studies were uncontrolled observational studies, and no randomized controlled trials were available for analysis.
Additionally, factors such as concomitant use of antiepileptic drugs (AED.
, additional treatments or changes during KDT, additional diets, dose reduction, and reasons for diet discontinuation or adverse effects were not consistently detailed, which may have influenced the effectiveness of KDT.
Further research is needed, particularly high-quality trials comparing KDT to placebo or combination Additionally, publication bias against negative results of KDT should be Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023.
: 36-44 | 10.
51559/pedscij.
REVIEW
Our meta-analysis significant heterogeneity due to various factors, including seizure type, epilepsy syndrome, types of KDT, additional diets, and concomitant use of AEDs.
Despite this heterogeneity, the findings remained statistically significant after applying the binary random effects model.
REFERENCES
CONCLUSION
Our review suggests that ketogenic diet therapy (KDT) demonstrates potential as an effective and well-tolerated therapy for epilepsy in infants.
However, wellconducted randomized controlled trials (RCT.
comparing KDT to a placebo or a combination of KDT and AED are needed to validate these findings further and strengthen the evidence base.
Additionally, further analysis is necessary to control for confounding factors.
DISCLOSURES
Funding The authors declare that there is no funding sources, grant, or third-party support in the making of this research.
Conflict of Interest The authors declare that they have no conflict of interest.
Author Contribution All authors designed the research.
NAT,
SM, and DC did the research.
NAT and PA did the statistical analysis.
NAT and SM wrote the first draft, and all authors contributed to writing the final report.
ACKNOWLEDGMENTS