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Pediatric Obesity

      The divide between those who have and those who do not is most often discussed in terms of personal wealth, but access to food and clean water is equally disparate. Currently, millions of children routinely go to bed hungry. Most of these children live in the developing world, but in the United States “over 15 million children live in food insecure households.”

      Feeding America. http://www.feedingamerica.org. Accessed August 6, 2015

      Although undernutrition is equally or perhaps even more important, the focus of this issue of Clinical Therapeutics is on the effects of overnutrition, that is, pediatric obesity.
      Although millions of children in the world are starving, the number of obese and morbidly obese US children continues to increase at epidemic rates.

      Centers for Disease Control and Prevention. Childhood Obesity Facts. http://www.CDC.gov/healthyyouth/obesity/facts.htm. Accessed August 6, 2015.

      There are more than twice as many children and up to 4 times as many obese adolescents than there were 30 years ago, and in 2012 as many as 1 in 3 children and adolescents was overweight or obese. Although somewhat less rapidly, this increase is also occurring in many other “developed” countries.

      European Association for the Study of Obesity. http://www.easo.org. Accessed August 6, 2015.

      The causes, consequences, prevention, and treatment of pediatric obesity are the subject of numerous studies, interventions, and publications. For example, a recent PubMed search that used the terms “obesity AND pediatric OR paediatric” yielded 353,167 hits.
      The first 2 articles in this issue discuss the implications of obesity on dosing medications in children. The first, by Kendrick et al,
      • Kendrick J.G.
      • Carr R.R.
      Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing.
      is an update of a review of medication dosing in obese children. Such an update seemed desirable on the basis of the increase in interest in this topic, including an article by Le et al,
      • Le J.
      • Capparelli J.V.
      • Wahid U.
      • et al.
      Bayesian estimation of vancomycin pharmacokinetics in obese children: matched case-control study.
      also published in the journal, that used Bayesian estimation to show that actual weight and allometric weight (weight to the 0.75 power) can both be used to estimate Vd and CL of vancomycin in obese children. Both Vd and CL were slightly lower than found in nonobese control children, and the authors felt the estimates “were unlikely to be clinically relevant.”
      • Le J.
      • Capparelli J.V.
      • Wahid U.
      • et al.
      Bayesian estimation of vancomycin pharmacokinetics in obese children: matched case-control study.
      As Kendrick et al
      • Kendrick J.G.
      • Carr R.R.
      Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing.
      describe, this is not true for the effects of obesity on dosing of some medications, especially medications for which, unlike vancomycin, dosing is not routinely adjusted on the basis of therapeutic drug-monitoring results. The review by Kendrick et al
      • Kendrick J.G.
      • Carr R.R.
      Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing.
      concluded that there is limited, often suboptimal, data available on dosing of obese pediatric patients, making it necessary to extrapolate from data in obese adults. The second article, by Rowe et al,
      • Rowe S.
      • Siegel D.
      • Benjamin Jr, D.K.
      Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
      suggests that this approach is seldom likely to be useful.
      The article by Rowe et al
      • Rowe S.
      • Siegel D.
      • Benjamin Jr, D.K.
      Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
      focuses on the gaps in knowledge about dosing of acute care medications in obese children. These authors selected 25 acute care drugs from the Strategic National Stockpile and the Acute Care Supportive Drugs List. They found a major difference (8% vs 88%, respectively) of these drugs had information in their labels on dosing of obese children versus obese adults. They were also able to find sufficient published PK data to dose obese adults with only 3 of 25 drugs (12%), but published PK data adequate to dose obese children was unavailable to all 25 acute drugs, suggesting that the “extrapolation from obese adults” approach suggested by Kendrick et al
      • Kendrick J.G.
      • Carr R.R.
      Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing.
      is unlikely to be successful in the acute care setting where appropriate dosing is most likely to be critical to patient outcomes. They concluded that priority should be given to correcting this deficiency.
      • Rowe S.
      • Siegel D.
      • Benjamin Jr, D.K.
      Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
      The third article, by Mihalopoulos and Spigarelli,
      • Mihalopoulos N.L.
      • Spigarelli M.G.
      Co-management of pediatric depression and obesity: a systematic review.
      reviews the disappointingly scarce literature on comorbid depression in obese adolescents. In many ways adolescents pharmacologically resemble adults more than they do children. However, they are also unique in their susceptibility to a number of conditions, including comorbid psychiatric conditions. Although one of our reviewers of this study felt that adult data for comorbid obesity and depression should have been relied on more for treatment of adolescents, in my view there are many reasons to suspect that adolescents could differ in their response to obesity, to its psychosocial effects, and, perhaps also, to its treatment. It is unfortunate that, as shown by Mihalopoulos and Spigarelli,
      • Mihalopoulos N.L.
      • Spigarelli M.G.
      Co-management of pediatric depression and obesity: a systematic review.
      so little has been done to investigate these questions.
      The fourth and final article by Siegel et al
      • Siegel R.M.
      • Anneken A.
      • Duffy C.
      • et al.
      Emoticon use increases plain milk and vegetable purchase in a school cafeteria without adversely affecting total milk purchase.
      describes results of a controlled trial of what appears to be an effective, easily implemented, school cafeteria-based method to improve food choices. Obesity prevention with the use of low-cost but effective behavioral modification techniques such as this could be both more cost effective and well tolerated than either medication or surgical treatments. Antibiotics are used as growth promoters in animals, suggesting that possible preventative approaches might include decreasing exposure to unnecessary antibiotics. Childhood antibiotic exposure has been reported to be associated with both higher incidence of obesity in resource-rich countries
      • Saari A.
      • Virta L.J.
      • Sankilampi U.
      • et al.
      Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life.
      and a potential treatment for malnutrition in resource-poor settings
      • Trehan I.
      • Goldbach H.S.
      • LaGrone L.N.
      • et al.
      Antibiotics as part of the management of severe acute malnutrition.
      . Of note, Dr Siegel has also published on the use of “safety net antibiotic prescriptions” to decrease unnecessary antibiotic use in children with otitis media.
      • Siegel R.M.
      • Bien J.
      • Lichtenstein P.
      • et al.
      A safety-net antibiotic prescription for otitis media: the effects of a PBRN study on patients and practitioners.
      Clearly, much needs to be done to prevent and correct the various forms of pediatric malnutrition which are increasingly common throughout the world, including both starvation and obesity. Clinical Therapeutics welcomes publications that deal with any aspect of the causes, prevention, or treatment of either overnutrition or undernutrition in either children or adults.

      References

      1. Feeding America. http://www.feedingamerica.org. Accessed August 6, 2015

      2. Centers for Disease Control and Prevention. Childhood Obesity Facts. http://www.CDC.gov/healthyyouth/obesity/facts.htm. Accessed August 6, 2015.

      3. European Association for the Study of Obesity. http://www.easo.org. Accessed August 6, 2015.

        • Kendrick J.G.
        • Carr R.R.
        Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing.
        Clin Ther. 2015; 37: 1897-1923
        • Le J.
        • Capparelli J.V.
        • Wahid U.
        • et al.
        Bayesian estimation of vancomycin pharmacokinetics in obese children: matched case-control study.
        Clin Ther. 2015; 37: 1340-1351
        • Rowe S.
        • Siegel D.
        • Benjamin Jr, D.K.
        Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
        Clin Ther. 2015; 37: 1924-1932
        • Mihalopoulos N.L.
        • Spigarelli M.G.
        Co-management of pediatric depression and obesity: a systematic review.
        Clin Ther. 2015; 37: 1934-1937
        • Siegel R.M.
        • Anneken A.
        • Duffy C.
        • et al.
        Emoticon use increases plain milk and vegetable purchase in a school cafeteria without adversely affecting total milk purchase.
        Clin Ther. 2015; 37: 1938-1943
        • Saari A.
        • Virta L.J.
        • Sankilampi U.
        • et al.
        Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life.
        Pediatrics. 2015; 135: 617-626
        • Trehan I.
        • Goldbach H.S.
        • LaGrone L.N.
        • et al.
        Antibiotics as part of the management of severe acute malnutrition.
        N Engl J Med. 2013; 368: 425-435
        • Siegel R.M.
        • Bien J.
        • Lichtenstein P.
        • et al.
        A safety-net antibiotic prescription for otitis media: the effects of a PBRN study on patients and practitioners.
        Clin Pediatr. 2006; 45: 518-524