title: Obesity and overweight as CAE comorbidities and differential drug response modifiers.
abstract: OBJECTIVE
  This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution.
  
  
  METHODS
  Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary intake were standardized for age, sex, and race/ethnicity and compared to age-matched US population from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models tested BMI as a predictor of treatment response. Pharmacokinetic variables were explored as contributors to differential drug response.
  
  
  RESULTS
  After standardizing for demographic differences, children with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p < 0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE group than in NHANES controls. With increasing baseline BMI z score, the efficacy and effectiveness of ethosuximide and valproic acid over lamotrigine became more pronounced, despite no significant differences in drug exposure and trough levels.
  
  
  CONCLUSIONS
  Overweight and obesity are more prevalent in children with newly diagnosed CAE than in age-matched peers, despite lower caloric and carbohydrate intake. Baseline BMI may also predict differential drug response, which cannot be attributed to pharmacokinetic differences.
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY. ravindra.arya@cchmc.org.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Arya
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Gillespie
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Avital
authors.initials: A
authors.lastname: Cnaan
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Mahima
authors.initials: M
authors.lastname: Devarajan
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Peggy
authors.initials: P
authors.lastname: Clark
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Shinnar
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Kana
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Glauser
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D057186:Comparative Effectiveness Research; D004032:Diet; D004311:Double-Blind Method; D002149:Energy Intake; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000453:epidemiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000453:epidemiology*; D050177:Overweight / Q000453:epidemiology* / Q000378:metabolism; D015995:Prevalence; D017211:Treatment Failure
chemical_list: D000927:Anticonvulsants