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      Practical Challenges—Use of Paracetamol in Children and Youth Who are Overweight or Obese: A Narrative Review

      review-article
      1 , , 2 , 2
      Paediatric Drugs
      Springer International Publishing

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          Abstract

          Worldwide, > 380 million children and adolescents are overweight or obese, including 41 million children aged < 5 years. Obesity can change the pharmacokinetic properties of drugs by altering their distribution, metabolism, and elimination. Thus, children who are overweight or obese are at increased risk for receiving inappropriate doses of commonly used drugs, which can result in treatment failure, adverse events, and/or drug toxicity. This review analyzes available data on paracetamol dosing for pain and fever in children and adolescents who are overweight or obese to identify gaps and challenges in optimal dosing strategies. Literature searches using Medline, Embase, and ClinicalTrials.gov were conducted to identify English-language articles reporting paracetamol pharmacokinetics, dosing practices, and guidelines in children and adolescents who are overweight or obese. Of 24 relevant studies identified, 20 were specific to overweight/obese individuals and 15 were specific to children and/or adolescents. Data on paracetamol pharmacokinetics in children and adolescents who are overweight or obese are lacking, and there is no high-quality evidence to guide paracetamol prescribing practices in these patients. Adult data have been extrapolated to pediatric populations; however, extrapolation does not address differences in paracetamol metabolism in adults versus children; the efficacy and safety effects of such differences are unknown. Given the growing worldwide prevalence of obesity in children and adolescents and the likelihood that paracetamol use in this population will increase accordingly, obesity-specific pediatric dosing guidelines for paracetamol are urgently needed. High-quality research is necessary to inform such guidelines.

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          Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults

          Summary Background Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. Methods We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5–19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5–19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). Findings Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (−0·01 kg/m2 per decade; 95% credible interval −0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69–1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64–1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (−0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50–1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4–1·2) in 1975 to 5·6% (4·8–6·5) in 2016 in girls, and from 0·9% (0·5–1·3) in 1975 to 7·8% (6·7–9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0–12·9) in 1975 to 8·4% (6·8–10·1) in 2016 in girls and from 14·8% (10·4–19·5) in 1975 to 12·4% (10·3–14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7–29·6) among girls and 30·7% (23·5–38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44–117) million girls and 117 (70–178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24–89) million girls and 74 (39–125) million boys worldwide were obese. Interpretation The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. Funding Wellcome Trust, AstraZeneca Young Health Programme.
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            Establishing a standard definition for child overweight and obesity worldwide: international survey.

            To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. International survey of six large nationally representative cross sectional growth studies. Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. 97 876 males and 94 851 females from birth to 25 years of age. Body mass index (weight/height(2)). For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m(2) for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years. The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
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              Development of a WHO growth reference for school-aged children and adolescents.

              To construct growth curves for school-aged children and adolescents that accord with the WHO Child Growth Standards for preschool children and the body mass index (BMI) cut-offs for adults. Data from the 1977 National Center for Health Statistics (NCHS)/WHO growth reference (1-24 years) were merged with data from the under-fives growth standards' cross-sectional sample (18-71 months) to smooth the transition between the two samples. State-of-the-art statistical methods used to construct the WHO Child Growth Standards (0-5 years), i.e. the Box-Cox power exponential (BCPE) method with appropriate diagnostic tools for the selection of best models, were applied to this combined sample. The merged data sets resulted in a smooth transition at 5 years for height-for-age, weight-for-age and BMI-for-age. For BMI-for-age across all centiles the magnitude of the difference between the two curves at age 5 years is mostly 0.0 kg/m(2) to 0.1 kg/m(2). At 19 years, the new BMI values at +1 standard deviation (SD) are 25.4 kg/m(2) for boys and 25.0 kg/m(2) for girls. These values are equivalent to the overweight cut-off for adults (> or = 25.0 kg/m(2)). Similarly, the +2 SD value (29.7 kg/m(2) for both sexes) compares closely with the cut-off for obesity (> or = 30.0 kg/m(2)). The new curves are closely aligned with the WHO Child Growth Standards at 5 years, and the recommended adult cut-offs for overweight and obesity at 19 years. They fill the gap in growth curves and provide an appropriate reference for the 5 to 19 years age group.
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                Author and article information

                Contributors
                wzempsk@connecticutchildrens.org
                Journal
                Paediatr Drugs
                Paediatric Drugs
                Springer International Publishing (Cham )
                1174-5878
                1179-2019
                11 September 2020
                11 September 2020
                2020
                : 22
                : 5
                : 525-534
                Affiliations
                [1 ]GRID grid.63054.34, ISNI 0000 0001 0860 4915, Department of Pediatrics, Connecticut Children’s Medical Center, , University of Connecticut, ; 282 Washington St, Hartford, CT 06106 USA
                [2 ]Consumer Healthcare R & D, GlaxoSmithKline Consumer Healthcare, Singapore, Singapore
                Article
                417
                10.1007/s40272-020-00417-z
                7529628
                32918268
                f68c9f4f-400e-4119-b5cb-49f3cf01cd44
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Funding
                Funded by: GlaxoSmithKline Consumer Healthcare
                Categories
                Review Article
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                © Springer Nature Switzerland AG 2020

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