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Body mass index reference charts for individuals with Down syndrome aged 2-18 years Please cite this article as: Bertapelli F, Machado MR, Roso RV, Guerra-Júnior G. Body mass index reference charts for individuals with Down syndrome aged 2-18 years. J Pediatr (Rio J). 2017;93:94-9. ,☆☆ ☆☆ Study carried out at Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Abstract:

Objective:

To develop Brazilian growth charts for body mass index (BMI-for-age) for individuals with Down syndrome (DS). The secondary objective was to compare the BMI-for-age with the Centers for Disease Control and Prevention standards (CDC).

Methods:

A retrospective and cross-sectional growth study of 706 youth with DS (56.7% males) was performed in 51 centers in São Paulo state, Brazil. Weight and height were used to calculate the BMI (kg/m2). The LMS method was applied to construct the growth charts. Z-scores were based on the CDC 2000 growth standards.

Results:

The BMI-for-age reference charts showed excellent goodness of fit statistics for boys and girls with DS aged 2-18 years. At 2 years of age, the mean BMI Z-scores of boys and girls with DS were lower compared to those of the CDC (Z-score = −0.2). In contrast, children with DS aged 3-18 years had higher mean Z-scores for BMI-for-age when compared to those of the CDC (Z-scores = +0.2 to +1.3).

Conclusions:

The BMI of Brazilian youth with DS differs from those references established by CDC. These are the first Brazilian BMI-for-age charts for individuals with DS and will hopefully guide clinicians and parents in the evaluation and management of the nutritional status in children and adolescents with DS in Brazil.

KEYWORDS
Trisomy 21; Body mass index; Weight; Height; Growth charts; Nutritional status

Resumo:

Objetivo:

Desenvolver curvas específicas de índice de massa corporal (IMC-para-idade) para população brasileira com síndrome de Down (SD). O objetivo secundário foi comparar os valores de IMC-para-idade com os valores normativos dos Centros de Controle e Prevenção de Doenças dos Estados Unidos (CDC).

Métodos:

Estudo do tipo retrospectivo e transversal. A amostra foi constituída de 706 jovens com SD (56,7%, meninos) recrutados em 51 instituições no Estado de São Paulo, Brasil. Peso e estatura foram obtidos e empregados para o cálculo de IMC (Kg/m2). O método LMS foi usado para a construção das curvas. Escores Z foram calculados com base na referência do CDC 2000.

Resultados:

As curvas de referência de IMC-para-idade para meninos e meninas com SD na faixa entre 2-18 anos apresentaram excelente ajuste estatístico. Aos 2 anos, o escore Z médio IMC de crianças com SD apresentou-se menor quando comparado com o CDC (escore Z = -0,2). Em contraste, os escores Z médios de IMC de jovens com SD foram superiores entre 3-18 anos (escores Z = +0,2 a +1,3).

Conclusões:

A população brasileira com SD apresentou diferentes padrões de IMC quando comparada com as referências do CDC. As curvas desenvolvidas neste estudo representam a primeira referência nacional de IMC-para-idade para jovens com SD. Espera-se, portanto, que essas curvas possam guiar pais e profissionais na avaliação do estado nutricional de crianças e adolescentes com SD no território brasileiro.

PALAVRAS-CHAVE
Trissomia 21; Índice de massa corporal; Peso; Estatura; Curvas de crescimento; Estado nutricional

Introduction

Down syndrome (DS) is a chromosomal disorder with an approximate incidence between 3.05 and 14 cases per 10,000 live births in the United States and China.11 Deng C, Yi L, Mu Y, Zhu J, Qin Y, Fan X, et al. Recent trends in the birth prevalence of Down syndrome in China: impact of prenatal diagnosis and subsequent terminations. Prenat Diagn. 2015;35:311-318.,22 Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, et al. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A: Clin Mol Teratol. 2010;88:1008-1016. Recent studies have shown a population prevalence between 6.1 and 13.1 per 10,000 persons.33 de Graaf G, Vis JC, Haveman M, van Hove G, de Graaf EAB, Tijssen JGP, et al. Assessment of prevalence of persons with Down syndrome: a theory based demographic model. J Appl Res Intellect Disabil. 2011;24:247-262.,44 Presson AP, Partyka G, Jensen KM, Devine OJ, Rasmussen SA, McCabe LL, et al. Current estimate of Down Syndrome population prevalence in the United States. J Pediatr. 2013;163:1163-1168. The life expectancy of individuals with DS has increased considerably over the past years. A study suggests that 94.4% of children with DS born in 2000 will survive up to 2020, 90.8% up to 2030, and 76.3% up to 2050.33 de Graaf G, Vis JC, Haveman M, van Hove G, de Graaf EAB, Tijssen JGP, et al. Assessment of prevalence of persons with Down syndrome: a theory based demographic model. J Appl Res Intellect Disabil. 2011;24:247-262. Life expectancy is linked to the development of research and services provided to this population.55 Day SM, Strauss DJ, Shavelle RM, Reynolds RJ. Mortality and causes of death in persons with Down syndrome in California. Dev Med Child Neurol. 2005;47:171-176. Despite these advances, children with DS have health conditions that affect their quality of life, including congenital heart disease, hypothyroidism, gastrointestinal disorders, and obstructive sleep apnea.66 Roizen NJ, Magyar CI, Kuschner ES, Sulkes SB, Druschel C, van Wijngaarden E, et al. A community cross-sectional survey of medical problems in 440 children with Down syndrome in New York State. J Pediatr. 2014;164:871-875. According to the guidelines of the American Academy of Pediatrics and of the Brazilian Ministry of Health, individuals with DS also have growth restriction and overweight.77 Brasil, Ministério da Saúde, Secretaria de Atenção à Saúde, Departamento de Ações Programáticas e Estratégicas. Diretrizes de atenção à pessoa com Síndrome de Down (Série F. Comunicação e Educação em Saúde). Brasília: Ministério da Saúde; 2012, v.1.,88 Bull MJ. Health supervision for children with Down syndrome. Pediatrics. 2011;128:393-406.

The adequate monitoring of the nutritional status of youth with DS helps to prevent and identify overall health problems. The body mass index (BMI) is a health indicator that is commonly used to classify the nutritional status of children, adults, and the elderly. The Centers for Disease Control and Prevention (CDC) has recommended the use of BMI to assess the health status of children older than 2 years. However, youth with DS have different weight, height, and BMI standards when compared to children in the general population without DS.99 Bertapelli F, Martin JE, Goncalves EM, de Oliveira Barbeta VJ, Guerra-Junior G. Growth curves in Down syndrome: implications for clinical practice. Am J Med Genet Part A. 2014;164A:844-847.

Youth with DS aged 2-20 years had lower height and higher BMI when compared to the CDC charts, suggesting the need for specific growth charts for youth with DS.1010 Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136:e1204-e1211. In Brazil, the Ministry of Health recommends the use of the weight-for-age charts by Cronk et al.1111 Cronk C, Crocker AC, Pueschel SM, Shea AM, Zackai E, Pickens G, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81:102-110. for monitoring the nutritional status of Brazilian youth with DS aged 2-18 years. These charts combine cross-sectional and longitudinal data including 730 U.S. individuals with DS aged 1 month to 18 years.1111 Cronk C, Crocker AC, Pueschel SM, Shea AM, Zackai E, Pickens G, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81:102-110. The clinical and practical use of these curves, however, had been questioned by the American Academy of Pediatrics.88 Bull MJ. Health supervision for children with Down syndrome. Pediatrics. 2011;128:393-406.

Due to the limitations of the existing charts and the absence of normative values of BMI-for-age for Brazilian youth with DS, this study aimed to develop Brazilian BMI-for-age charts for individuals with DS aged 2-18 years. The secondary objective was to compare the BMI-for-age of the study participants with the normative values established by the CDC/2000.

Methods

Children and adolescents with DS aged 2-18 years were recruited from a retrospective and cross-sectional study carried out between 2012 and 2015. The study was conducted at Universidade Estadual de Campinas, 48 specialized centers that provide care to individuals with intellectual disabilities, and two specialized centers for individuals with DS, all located in the state of São Paulo. The study was approved by the Ethics Committee of the Faculdade de Ciências Médicas of the Universidade Estadual de Campinas (No. 140.186/2012). An informed consent was signed by parents and guardians.

Clinical data records were obtained through interviews with families and from medical records. A questionnaire was applied to parents and guardians, including information on age, sex, gestational age, comorbidities, medications, weight, height, and head circumference. During the interview (2012-2014), information was also obtained from the Child Health record Card and questionnaires provided to parents (by healthcare facilities, medical clinics, and hospitals in the city of Campinas). Weight and height were measured by a trained team. Participants were measured barefoot and wearing light clothes. In Campinas, height was measured using a portable stadiometer, model E210 (Wiso®, SC, Brazil). Weight was measured using a digital scale, model W801 (Wiso®, SC, Brazil).

Data screening was carried out in different stages: 1) We excluded duplicated data based on identification code, birthdate, and measurement date; 2) We removed outliers (five standard deviations above or below the mean); 3) We excluded data points demonstrating loss of height over time. The questionnaires and clinical records were reviewed and data inconsistencies were resolved. Weight and height data were used to calculate BMI using the following formula: BMI = weight divided by height squared (kg/m2). Generalized additive models for location, scale and shape (GAMLSS)1212 Stasinopoulos DM, Rigby RA. Generalized additive models for location scale and shape (GAMLSS) in R. J Stat Softw. 2007;23:1-46. were used for the construction of the BMI-for-age curves, using the R software (R Foundation for Statistical Computing, version 3.2.2, Vienna, Austria). The LMS method and worm plots were used for modeling the curves.1313 van Buuren S, Fredriks M. Worm plot: a simple diagnostic device for modelling growth reference curves. Stat Med. 2001;20:1259-1277.,1414 Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med. 1992;11:1305-1319.

The percentiles generated for BMI-for-age were: 5th, 10th, 25th, 50th, 75th, 85th, 90th, and 95th. Mean Z-scores were calculated to compare the BMI-for-age with the normative references established by the CDC,1515 Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat. 2002;11:1-190. according to the following equation: Z = [(X/M)L 1]/L*S, where X is the observed measurement (BMI) of each participant, M is the median, L is the skewness, −1 is the constant, and S is the coefficient of variation. The values of L, M, and S were obtained from CDC/2000 normative charts.

Results

Participants

The sample consisted of 706 individuals with DS aged 2-18 years born between 1978 and 2012 (56.7% males). A total of 1,986 BMI data points were used to construct the charts. Preterm infants were 10.1% (<37 weeks gestation). A total of 17.9% had congenital heart disease, 13.1% had undergone cardiac surgery, and 22% had hypothyroidism (all controlled through laboratory tests). Missing data for gestational age, heart disease, and hypothyroidism were 57.9%, 31.3%, and 27.2%, respectively.

BMI charts

The reference charts of BMI-for-age for boys and girls with DS aged 2-18 years showed excellent goodness of fit statistics. Most subjects showed more than a single data point (82%). The number of data points, means, standard deviations, LMS, and percentiles for age and sex are shown in Tables 1 and 2. BMI-for-age charts of boys and girls with DS can be seen in Figs. 1 and 2. At 2 years of age, the mean BMI Z-score of children with DS was lower compared to the normative values of the CDC (Z-score = −0.2). In contrast, mean BMI Z-scores of children and adolescents with DS were higher at ages 3-18 years (Z-scores = +0.2 to +1.3).

Figure 1
Body mass index (BMI) curves for male children and adolescents with Down syndrome aged 2-18 years.

Figure 2
Body mass index (BMI) curves for female children and adolescents with Down syndrome aged 2-18 years.

Table 1
Body mass index (BMI) values of male children and adolescents with Down syndrome aged 2-18 years.
Table 2
Body mass index (BMI) values of female children and adolescents with Down syndrome aged 2-18 years.

Discussion

This study depicts the first Brazilian BMI-for-age charts for children and adolescents with DS aged 2-18 years. The study also found differences in BMI among the children and adolescents with DS enrolled in the present study and the normative values established by the CDC. The results have clinical and practical implications regarding the monitoring of the nutritional status of children and adolescents with DS in Brazil.

At 2 years of age, the mean BMI values of boys and girls with DS were below the standards established by the CDC. Studies show that children with DS are characterized by reduced body weight during the first two years of life.1010 Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136:e1204-e1211.,1616 Morris JK, Cole TJ, Springett AL, Dennis J. Down syndrome birth weight in England and Wales: implications for clinical practice. Am J Med Genet Part A. 2015;167:3070-3075. Low birthweight may be related to growth restriction and food intake disorders.1717 Weisz B, David AL, Chitty L, Peebles D, Pandya P, Patel P, et al. Association of isolated short femur in the mid-trimester fetus with perinatal outcome. Ultrasound Obstet Gynecol. 2008;31:512-516.,1818 Spender Q, Stein A, Dennis J, Reilly S, Percy E, Cave D. An exploration of feeding difficulties in children with Down syndrome. Dev Med Child Neurol. 1996;38:681-694. Growth restriction is related to genetic factors.1919 Blazek JD, Malik AM, Tischbein M, Arbones ML, Moore CS, Roper RJ. Abnormal mineralization of the Ts65Dn Down syndrome mouse appendicular skeleton begins during embryonic development in a Dyrk1a-independent manner. Mech Dev. 2015;136:133-142. Suction/swallowing disorders are associated with muscle hypotonia and dysfunctions in the oral motor system.1818 Spender Q, Stein A, Dennis J, Reilly S, Percy E, Cave D. An exploration of feeding difficulties in children with Down syndrome. Dev Med Child Neurol. 1996;38:681-694. After 2 years of age, the mean BMI-for-age Z-scores of children and adolescents with DS resulted in approximately one standard deviation above the normative values of the CDC. Zemel et al.1010 Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136:e1204-e1211. also reported higher values of BMI-for-age in U.S. children with DS after 2 years of age when compared to CDC standards. After that age, children with DS are likely to have higher prevalence of overweight and obesity when compared to children in the general population without DS.2020 Van Gameren-Oosterom HB, Van Dommelen P, Schonbeck Y, Oudesluys-Murphy AM, Van Wouwe JP, Buitendijk SE. Prevalence of overweight in Dutch children with Down syndrome. Pediatrics. 2012;130:e1520-e1526.,2121 Alexander M, Petri H, Ding Y, Wandel C, Khwaja O, Foskett N. Morbidity and medication in a large population of individuals with Down syndrome compared to the general population. Dev Med Child Neurol. 2016;58:246-254. Risk factors for obesity in DS include leptin hormone disorders, decreased resting energy expenditure, unbalanced diet, and low levels of physical activity.2222 Magge SN, O'Neill KL, Shults J, Stallings VA, Stettler N. Leptin levels among prepubertal children with Down syndrome compared with their siblings. J Pediatr. 2008;152:321-326.

23 Hill DL, Parks EP, Zemel BS, Shults J, Stallings VA, Stettler N. Resting energy expenditure and adiposity accretion among children with Down syndrome: a 3-year prospective study. Eur J Clin Nutr. 2013;67:1087-1091.

24 O'Neill KL, Shults J, Stallings VA, Stettler N. Child-feeding practices in children with down syndrome and their siblings. J Pediatr. 2005;146:234-238.
-2525 Pitetti K, Baynard T, Agiovlasitis S. Children and adolescents with Down syndrome, physical fitness and physical activity. J Sport Health Sci. 2013;2:47-57.

The percentiles of BMI-for-age of children with DS increased gradually in the age range from 2 to 18 years; a similar pattern was observed in the BMI-for-age percentiles of U.S. children with DS aged 2-20 years.1010 Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136:e1204-e1211. The uninterrupted increases in BMI observed in individuals with DS are not consistent with the BMI standards from the general population without DS. Growth international references show a rapid acceleration in median percentiles of BMI-for-age in the first year of life, followed by a decline until the age of 5 years, and a reacceleration at later ages.1515 Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat. 2002;11:1-190.,2626 de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;85:660-667.,2727 WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76-85.

These BMI-for-age curves are descriptive standards of growth in children and adolescents with DS. However, these curves do not indicate an optimal standard of weight, to which all children with DS should grow. The use these curves, however, allows for comparison and monitoring of body weight status of individuals with DS in Brazil.

The Brazilian Ministry of Health recommends using the weight-for-age charts by Cronk et al.1111 Cronk C, Crocker AC, Pueschel SM, Shea AM, Zackai E, Pickens G, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81:102-110. for monitoring the nutritional status of Brazilian children with DS. However, the clinical applicability has been questioned by the American Academy of Pediatrics.88 Bull MJ. Health supervision for children with Down syndrome. Pediatrics. 2011;128:393-406. The distribution of BMI-for-age percentiles among the population of this study and the CDC has shown differences from the practical standpoint. For example, a male child with DS aged 14 years (BMI: 23.85 kg/m2, 50th percentile, see Table 1) would be classified in the overweight category by the CDC/BMI parameters (CDC/BMI: 22.66 kg/m2, 85th percentile). The results suggest that further studies are needed to examine the association between BMI cutoffs and the overall health of children and adolescents with DS.

This study has some limitations. First, the data were obtained from clinical records and may include measurement errors. However, the data screening was rigorously performed to minimize biases. Second, the sample was restricted to the state of São Paulo and does not represent the total population of children with DS in Brazil. Conversely, the state of São Paulo, with an estimated population of 44,035,304 individuals (21.7% of Brazil) can represent the economic and ethnical diversity of the country. Finally, the curves do not represent the optimal growth status of children with DS, considering that some growth-influencing factors were not controlled, such as breastfeeding, lactation support, comorbidities, maternal health, and socioeconomic status. Further studies should investigate the association between these factors and the growth of children and adolescents with DS.

In conclusion, the Brazilian individuals with DS showed different BMI-for-age when compared to CDC references. The curves developed in this study represent the first national reference of BMI-for-age for youth with DS. Therefore, it is expected that these curves can guide parents and professionals in assessing the nutritional status of children and adolescents with DS in Brazil.

  • Funding
    Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
  • Please cite this article as: Bertapelli F, Machado MR, Roso RV, Guerra-Júnior G. Body mass index reference charts for individuals with Down syndrome aged 2-18 years. J Pediatr (Rio J). 2017;93:94-9.
  • ☆☆
    Study carried out at Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.

Acknowledgments

The authors received financial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES - BEX 3546/15-2) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (PIBIC - CNPq). The authors would like to thank Roberto A. Soares, João F. Cosmo, Alessandra C.P.D. Costa, Eliane T. Nogueira, Fabio Crozara, Célia de Oliveira, and Maria A. C. Pacheco for their excellent technical assistance. The authors would also like to thank the Associações de Pais e Amigos dos Excepcionais do Estado de São Paulo (APAEs/SP), Outpatient Clinic of Pediatric Specialty Integration of Faculdade de Ciências Médicas, Universidade Estadual de Campinas (AIEP/FCM/UNICAMP), Department of Medical Genetics (DGM/FCM/UNICAMP), Centro de Investigação em Pediatria (CIPED/FCM/Unicamp), Federação das APAEs do Estado de São Paulo (FEAPAES/SP), Centro de Educação Especial Síndrome de Down (CEESD), and Fundação Síndrome de Down (FSD) for their fundamental collaboration in this study.

References

  • 1
    Deng C, Yi L, Mu Y, Zhu J, Qin Y, Fan X, et al. Recent trends in the birth prevalence of Down syndrome in China: impact of prenatal diagnosis and subsequent terminations. Prenat Diagn. 2015;35:311-318.
  • 2
    Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, et al. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A: Clin Mol Teratol. 2010;88:1008-1016.
  • 3
    de Graaf G, Vis JC, Haveman M, van Hove G, de Graaf EAB, Tijssen JGP, et al. Assessment of prevalence of persons with Down syndrome: a theory based demographic model. J Appl Res Intellect Disabil. 2011;24:247-262.
  • 4
    Presson AP, Partyka G, Jensen KM, Devine OJ, Rasmussen SA, McCabe LL, et al. Current estimate of Down Syndrome population prevalence in the United States. J Pediatr. 2013;163:1163-1168.
  • 5
    Day SM, Strauss DJ, Shavelle RM, Reynolds RJ. Mortality and causes of death in persons with Down syndrome in California. Dev Med Child Neurol. 2005;47:171-176.
  • 6
    Roizen NJ, Magyar CI, Kuschner ES, Sulkes SB, Druschel C, van Wijngaarden E, et al. A community cross-sectional survey of medical problems in 440 children with Down syndrome in New York State. J Pediatr. 2014;164:871-875.
  • 7
    Brasil, Ministério da Saúde, Secretaria de Atenção à Saúde, Departamento de Ações Programáticas e Estratégicas. Diretrizes de atenção à pessoa com Síndrome de Down (Série F. Comunicação e Educação em Saúde). Brasília: Ministério da Saúde; 2012, v.1.
  • 8
    Bull MJ. Health supervision for children with Down syndrome. Pediatrics. 2011;128:393-406.
  • 9
    Bertapelli F, Martin JE, Goncalves EM, de Oliveira Barbeta VJ, Guerra-Junior G. Growth curves in Down syndrome: implications for clinical practice. Am J Med Genet Part A. 2014;164A:844-847.
  • 10
    Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136:e1204-e1211.
  • 11
    Cronk C, Crocker AC, Pueschel SM, Shea AM, Zackai E, Pickens G, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81:102-110.
  • 12
    Stasinopoulos DM, Rigby RA. Generalized additive models for location scale and shape (GAMLSS) in R. J Stat Softw. 2007;23:1-46.
  • 13
    van Buuren S, Fredriks M. Worm plot: a simple diagnostic device for modelling growth reference curves. Stat Med. 2001;20:1259-1277.
  • 14
    Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med. 1992;11:1305-1319.
  • 15
    Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat. 2002;11:1-190.
  • 16
    Morris JK, Cole TJ, Springett AL, Dennis J. Down syndrome birth weight in England and Wales: implications for clinical practice. Am J Med Genet Part A. 2015;167:3070-3075.
  • 17
    Weisz B, David AL, Chitty L, Peebles D, Pandya P, Patel P, et al. Association of isolated short femur in the mid-trimester fetus with perinatal outcome. Ultrasound Obstet Gynecol. 2008;31:512-516.
  • 18
    Spender Q, Stein A, Dennis J, Reilly S, Percy E, Cave D. An exploration of feeding difficulties in children with Down syndrome. Dev Med Child Neurol. 1996;38:681-694.
  • 19
    Blazek JD, Malik AM, Tischbein M, Arbones ML, Moore CS, Roper RJ. Abnormal mineralization of the Ts65Dn Down syndrome mouse appendicular skeleton begins during embryonic development in a Dyrk1a-independent manner. Mech Dev. 2015;136:133-142.
  • 20
    Van Gameren-Oosterom HB, Van Dommelen P, Schonbeck Y, Oudesluys-Murphy AM, Van Wouwe JP, Buitendijk SE. Prevalence of overweight in Dutch children with Down syndrome. Pediatrics. 2012;130:e1520-e1526.
  • 21
    Alexander M, Petri H, Ding Y, Wandel C, Khwaja O, Foskett N. Morbidity and medication in a large population of individuals with Down syndrome compared to the general population. Dev Med Child Neurol. 2016;58:246-254.
  • 22
    Magge SN, O'Neill KL, Shults J, Stallings VA, Stettler N. Leptin levels among prepubertal children with Down syndrome compared with their siblings. J Pediatr. 2008;152:321-326.
  • 23
    Hill DL, Parks EP, Zemel BS, Shults J, Stallings VA, Stettler N. Resting energy expenditure and adiposity accretion among children with Down syndrome: a 3-year prospective study. Eur J Clin Nutr. 2013;67:1087-1091.
  • 24
    O'Neill KL, Shults J, Stallings VA, Stettler N. Child-feeding practices in children with down syndrome and their siblings. J Pediatr. 2005;146:234-238.
  • 25
    Pitetti K, Baynard T, Agiovlasitis S. Children and adolescents with Down syndrome, physical fitness and physical activity. J Sport Health Sci. 2013;2:47-57.
  • 26
    de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;85:660-667.
  • 27
    WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76-85.

Publication Dates

  • Publication in this collection
    Jan/Feb 2017

History

  • Received
    11 Feb 2016
  • Accepted
    16 Apr 2016
Sociedade Brasileira de Pediatria Av. Carlos Gomes, 328 cj. 304, 90480-000 Porto Alegre RS Brazil, Tel.: +55 51 3328-9520 - Porto Alegre - RS - Brazil
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