Review article
Ketogenic diet guidelines for infants with refractory epilepsy

https://doi.org/10.1016/j.ejpn.2016.07.009Get rights and content

Highlights

  • Ketogenic diet treatment in infants with refractory epilepsy is effective and can be done safely.

  • Ketogenic diet must be adjusted to specific nutritional requirements of infants.

  • Monitoring during initiation and follow up is required by a multidisciplinary team.

Abstract

Background

The ketogenic diet (KD) is an established, effective non-pharmacologic treatment for drug resistant childhood epilepsy. For a long time, the KD was not recommended for use in infancy (under the age of 2 years) because this is such a crucial period in development and the perceived high risk of nutritional inadequacies. Indeed, infants are a vulnerable population with specific nutritional requirements. But current research shows that the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is often achieved and maintained in this specific patient group.

There is a need for standardised protocols and management recommendations for clinical use.

Method

In April 2015, a project group of 5 experts was established in order to create a consensus statement regarding the clinical management of the KD in infants. The manuscript was reviewed and amended by a larger group of 10 international experts in the KD field.

Consensus was reached with regard to guidance on how the diet should be administered and in whom.

Results

The resulting recommendations include patient selection, pre-KD counseling and evaluation, specific nutritional requirements, preferred initiation, monitoring of adverse effects at initiation and follow-up, evaluation and KD discontinuation.

Conclusion

This paper highlights recommendations based on best evidence, combined with expert opinions and gives directions for future research.

Section snippets

Introduction/background

The ketogenic diet (KD) is a non-pharmacologic treatment for children with drug resistant epilepsy. The efficacy of the KD has been established by several multicenter studies and one randomized controlled trial. The randomized trial that further established the efficacy of KD was conducted in children and adolescents aged 2–16 years.1 The diet may be administered in one of several ways and each may be valid. An international protocol for its implementation and subsequent follow-up management in

Methods

At the Dietary Management of Inherited Metabolic Diseases (DMIMD) conference 2015 in London an initial meeting was held with the goal of starting a working group of experts in KD treatment in infancy. A group of five experts (i.e two pediatric neurologist and three dietitians, see Appendix I) discussed issues with regard to specific recommendations for this group of patients and designed the framework based on subjects they found applicable. During teleconference calls several subjects were

Epilepsy syndromes in infancy where KD is of benefit

Management of epilepsy in infancy is challenging based on the characteristics of the epilepsy and its impact on neurodevelopment of the child. This implies early, aggressive and optimal treatment is warranted. As a non-pharmacological treatment KD is currently used in infants with refractory epilepsy syndromes (see Table 1) such as infantile spasms (West syndrome) resistant to first line medication,5, 6, 7, 8, 9 Ohtahara syndrome,10, 11 epilepsy of infancy with migrating seizures12 and

Preparing for treatment

Treatment with the KD is demanding for families and requires a high degree of medical and dietetic monitoring because of possible side effects and restrictiveness. A multidisciplinary team is highly recommended (pediatric neurologist/pediatrician, epilepsy nurse, dietitian and close cooperation with pharmacy).

At baseline detailed information is obtained on the medical, nutritional and biochemical status of the infant. After a positive decision an individualized KD and step by step plan will be

Which diet to choose and how to initiate

KD is a high fat (71–90% energy) and carbohydrate restricted (5–19% energy) diet that contains adequate amount of protein to support growth. Clinical practice shows the classical version of the KD with a 3:1 ratio is routinely used in infants in order to meet protein requirements. This means that for every 3 g of fat there is 1 g of combined protein and carbohydrate. Several studies show the range of KD ratio used is 2.5–4:1 with respect of tolerance, ketosis and side effects.5, 6, 7, 8

Baseline monitoring

Prior to the start of KD, laboratory and urine checks are strongly advised to ensure there are no pre-existing contra-indications or deficiencies (Table 5).

General

During diet initiation weight, nutritional intake, tolerance (i.e gastro intestinal disturbances, vomiting, etc.) are checked on a daily basis. Height and head circumference are measured at baseline.

While on a KD the infant can continue bottle feeding. In daily practice the majority of infants with severe epilepsy have feeding difficulties

Diet during emergency situations

The increased risk of hyperketosis should be considered during intercurrent illness. This is caused by reduced energy and carbohydrate intake in combination with elevated metabolism due to illness. Frequent testing of ketosis/blood glucose with use of additional carbohydrate as needed (additional Oral Rehydration Salt (ORS), glucose solution) is then required.

In calculating the allowed quantity of ORS/24 h, the carbohydrate level of the individual KD will initially be assumed. This is a

Evaluation and discontinuation

The overall aim of treatment is to reduce, if not control, epileptic seizures. To monitor this, it is important for seizures to be documented in a form of a diary. Further secondary gains may be aimed for such as reduction of AEDs, as well as increased alertness and attention, although neither of these gains can be predicted.

The aim of the treatment in case of infantile spasms (IS) varies according to the course of the disease. This is the most common seizure type in the first year of life.

Conclusions and remarks for future research

These guidelines represent the first international effort to identify commonalities in the clinical use of the KD in infants. All members of the project and review group agreed on most of the major issues in both choosing the best candidates for the KD, pre-diet counselling, supplementation, and the management of children on the KD in regards to nutrition, laboratory values, potential adverse effects, and eventual discontinuation. Areas of variability included choice of initial diet ratio, how

Disclosure

The project group was supported financially (travel and hotel costs only) to attend the meeting at the DMIMD 2015 in London. The project group composed of E. van der Louw, T. van den Hurk, E. Neal, S. Auvin and J. H. Cross has built their recommendations based on their own personal view and clinical experience and evidence, with no influence or editorial rights on the output by any company. E. Neal received an unrestricted grant by Nutricia, other members of the project group received no

Conflict of interest statement

We wish to confirm to the editor Dr. S.M. Zuberi that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. The project group composed of E. van der Louw, T. van den Hurk, E. Neal, S. Auvin and J. H. Cross has build their recommendations based on their own personal view and clinical experience and evidence, with no influence or editorial rights on the output by any

Acknowledgements

The authors thank Prof. Dr. Eric Kossoff, Nicole dos Santos, RD Ketogenic Dietitian, St George Hospital, London, UK and Christine Williams-Dyjur, RD, Pediatric Neurosciences, Ketogenic Diet Program, Alberta Children's Hospital, Canada for their expertise and contribution to the manuscript.

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