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      Growth in achondroplasia: Development of height, weight, head circumference, and body mass index in a European cohort

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          Abstract

          <p class="first" id="d13758711e158">As growth references for achondroplasia are limited to reports from United States, Japan, Argentina, and Australia, the aim of this study was to construct growth references for height, weight, head circumference, and body mass index (BMI) from a European cohort of children with achondroplasia and to discuss the development of these anthropometric variables. A mix of cross-sectional and longitudinal, retrospective, and prospective data from 466 children with achondroplasia and 4,375 measuring occasions were modeled with generalized additive model for location, scale and shape (GAMLSS) to sex-specific references for ages 0 to 20 years. Loss in height position, that is, reduction in height standard deviation scores, occurred mainly during first 2 years of life while pubertal growth seemed normal if related to adult height. Adult height was 132 cm in boys and 124 cm in girls with a variability comparable to that of the general population and seems to be remarkably similar in most studies of children with achondroplasia. BMI had a syndrome-specific development that was not comparable to BMI development in the general population. Weight and BMI might be misleading when evaluating, for example, metabolic health in achondroplasia. Head circumference reached adult head size earlier than in the general population. Increased tempo of head circumference growth necessitates thus close clinical follow-up during first postnatal years. </p>

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          Most cited references43

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          Development of a WHO growth reference for school-aged children and adolescents

          OBJECTIVE: 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. METHODS: 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. FINDINGS: 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/m² to 0.1 kg/m². At 19 years, the new BMI values at +1 standard deviation (SD) are 25.4 kg/m² for boys and 25.0 kg/m² for girls. These values are equivalent to the overweight cut-off for adults (> 25.0 kg/m²). Similarly, the +2 SD value (29.7 kg/m² for both sexes) compares closely with the cut-off for obesity (> 30.0 kg/m²). CONCLUSION: 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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            Generalized additive models for location, scale and shape (with discussion)

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              Smoothing reference centile curves: The lms method and penalized likelihood

              Refence centile curves show the distribution of a measurement as it changes according to some covariate, often age. The LMS method summarizes the changing distribution by three curves representing the median, coefficient of variation and skewness, the latter expressed as a Box-Cox power. Using penalized likelihood the three curves can be fitted as cubic splines by non-linear regression, and the extent of smoothing required can be expressed in terms of smoothing parameters or equivalent degrees of freedom. The method is illustrated with data on triceps skinfold in Gambian girls and women, and body weight in U.S.A. girls.
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                Author and article information

                Contributors
                Journal
                American Journal of Medical Genetics Part A
                Am J Med Genet Part A
                Wiley
                15524825
                August 2018
                August 2018
                August 02 2018
                : 176
                : 8
                : 1723-1734
                Affiliations
                [1 ]Department of Women's and Children's Health; Karolinska Institutet; Stockholm Sweden
                [2 ]Pediatric Endocrinology Unit; Karolinska University Hospital; Stockholm Sweden
                [3 ]Department of Quality, Research, Innovation & Education, Odense University Hospital; Odense Denmark
                [4 ]Department of Molecular Medicine and Surgery; Karolinska Institutet; Stockholm Sweden
                [5 ]Center for Molecular Medicine; Karolinska Institutet; Stockholm Sweden
                [6 ]Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden
                [7 ]Universitätskinderklinik, Otto-von-Guericke Universität; Magdeburg Germany
                Article
                10.1002/ajmg.a.38853
                30070757
                1ebabfab-d411-4194-a0e5-9fc38845e044
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

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