Use of ketogenic diet therapy in infants with epilepsy: A systematic review and meta‐analysis

Objective Ketogenic diet therapy (KDT) is a group of high-fat, low-carbohydrate diets used as an effective treatment option for children and adults with drug-resistant epilepsy. There is limited research on the efficacy of KDT in infants, where there is the highest incidence of onset of the epilepsy. We aimed to systematically review studies that have reported on response to KDT in infants with epilepsy. Methods An online comprehensive literature search was performed, including studies that provided seizure frequency data for at least one infant younger than 2 years of age who was treated with KDT for ≥1 month. The proportions of infants achieving ≥50% seizure reduction, seizure-freedom rates, retention rates, and reported side effects were extracted from studies. Meta-analyses were performed using a random-effects model, and subgroup analyses were performed to investigate possible between-study heterogeneity. Results Thirty-three studies met inclusion criteria and were included in the final analysis, with a total of 534 infants with efficacy data. Two studies were randomized-controlled trials, and the remainder were uncontrolled cohort studies. All studies were categorized as low quality. Meta-analyses of uncontrolled studies estimate 59% (95% confidence interval [CI] 53-65) of infants achieved ≥50% seizure reduction and 33% (95% CI 26-43) of infants achieved seizure freedom. Retention rates ranged from 84% at 3 months to 27% at 24 months. The most commonly reported side effects were dyslipidemia (20/171, 12%), vomiting (11/171, 6%), constipation (7/171, 4%), gastroesophageal reflux (6/171, 4%), and diarrhea (6/171, 4%). Significance This review indicates that KDT is safe and tolerable and that it can be an effective treatment option for infants with drug-resistant epilepsy. However, there are few studies focusing on infants treated with KDT, and high-quality evidence is lacking. High-quality randomized-controlled trials are needed to confirm the effectiveness, safety, and tolerability of dietary treatment in this vulnerable age group.