Serial correlation between saliva and blood beta-hydroxybutyrate levels in children commencing the ketogenic diet for epilepsy

Objectives: Accurate and user-friendly methods to measure beta-hydroxybutyrate (BHB) concentration are needed to guide the optimal use of ketogenic diet therapy (KDT). We aimed to determine the correlation between serum, capillary, and salivary BHB concentration, and to validate an electrochemical salivary BHB point-of-care test (POCT) in children commencing KDT for drug-resistant epilepsy. Methods: This was a single center, prospective cohort study. Children <18 years with drug-resistant epilepsy electively admitted to Shenzhen Children's Hospital to initiate KDT between January 1, 2020 and June 30, 2021, were included. Over the 7-day admission, we collected paired saliva and capillary blood samples twice a day and serum blood samples on the first and last days of admission from each participant. Salivary BHB was measured using liquid chromatography mass spectrometry (LCMS) and the POCT. Primary outcome was the correlation between serum and salivary BHB concentration measured using LCMS. Secondary outcomes were the correlation between both the capillary blood and salivary BHB concentration, measured by LCMS, and the POCT device. Results: Seventy-one serum and 334 capillary blood paired with salivary samples were collected from 42 children (median age 4.5 years, interquartile range 1 to 8 years, 45% female). Salivary BHB measured using LCMS strongly correlated with serum BHB (Spearman's ρ = 0.910) and capillary blood BHB concentrations (Spearman's ρ = 0.865). Salivary BHB concentration was 6% and 7% of serum and capillary blood BHB concentration, respectively. The POCT demonstrated excellent test–retest reliability when compared with LCMS (ICC(A,k) = 0.983, 95% confidence interval: 0.980–0.986). Salivary BHB concentration measured by the POCT showed good accuracy in predicting the capillary blood BHB concentration within the therapeutic range of 2–5 mM. Significance: Salivary BHB concentration strongly correlates with both serum and capillary blood BHB concentration. The POCT accurately measures salivary BHB concentration and provides a simple, user-friendly method to guide the use of KDT for children with drug-resistant epilepsy.