Mathematical methods in the assessment of human growth

Lead Research Organisation: University College London
Department Name: Unlisted

Abstract

Nearly all children grow, and healthy children grow well. This important principle distinguishes paediatrics from adult medicine, so that a simple and effective way to measure the health of children is to assess their size and growth over time. Growth charts are used throughout the world for this purpose by midwives, nurses, doctors and paediatricians, either at home, or the welfare clinic, doctor‘s surgery or in hospital. Growth is important in many areas of paediatrics and child health.

But growth assessment raises quite complex statistical questions about how the charts should be constructed and used. The grant aims to develop the science of growth assessment by building on previous work: improving statistical methods for their construction, devising new forms of chart to sharpen the assessment, and addressing underlying questions such as ‘What exactly is good growth?‘, or ‘Why are people taller now than last century?‘ or ‘How tall will my baby be?‘ A clue to the first question comes from babies followed up into later life, where their growth rate in infancy relates to their later health. There is increasing evidence that growing too fast too early leads to greater illness later, for reasons which are not well understood but which may relate to obesity. So this suggests that ‘good‘ growth is not necessarily ‘rapid‘ growth, and growth charts for babies should be able to test for this. Yet despite their name, growth charts are not good at measuring growth over time, instead they measure a child‘s size. This is just one area where the charts need to be improved.

Another area is child obesity, which has become a serious public health problem in recent years. Methods for measuring fatness, and for identifying overweight or obesity, involve similar statistical questions to those for growth, and are best answered by approaching them in the same way. For example recent work on the grant has led to a new definition of child obesity which is

Technical Summary

Statistical anthropometry involves the assessment of size and shape, and their ‘growth‘ or rate of change over time, during fetal, infant, child, pubertal and adult life; the adjustment of whole-body and body-compartment physiological measures for body size and shape during both child and adulthood; and the investigation of factors relating to these quantities, particularly the prediction of later health from earlier size and growth. They all raise statistical issues where analysis is strengthened by being approached in a unified way. Previous work on this grant has established a set of statistical principles which have led to widespread advances in the treatment of such anthropometry data: the LMS method for fitting age-related reference ranges, used to construct growth charts and to convert anthropometry to age-sex adjusted SD scores; and a general definition of conditional growth based on SD scores which allows growth as well as size to be assessed using conventional charts.

The aims of the proposed research are to (i) identify new public health and clinical areas where the statistical tools can be applied; (ii) provide new insights into aspects of growth and nutrition through application of the tools, and (iii) improve and extend the tools. One particular aim will be to address the anthropometric transition from child to adult, both in terms of size and growth. These aims will be pursued mainly through the analysis of pre-existing data, often provided by collaborators.

Examples under (i) are infant weight gain charts for ethnic minorities, Down‘s syndrome and those born very premature; height gain charts adjusted for pubertal stage; and prediction equations for basal metabolic rate in children and adults. Examples under (ii) are refining the definition of child obesity using body mass index (BMI) and better understanding its age-related changes; and clarifying the life course importance of early size and growth on later health outcome. Under (iii) tnt aims to extend the methodology of the LMS method, upgrade the Windows program that has been written to apply it, and explore ways of using the LMS method to determine sample size in growth surveys.

Publications

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Davies PS (1999) Vitamin D: seasonal and regional differences in preschool children in Great Britain. in European journal of clinical nutrition

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De Stavola BL (2006) Statistical issues in life course epidemiology. in American journal of epidemiology

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Dzwonek AB (2006) Body fat changes and lipodystrophy in HIV-infected children: impact of highly active antiretroviral therapy. in Journal of acquired immune deficiency syndromes (1999)

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Englyst KN (1999) Rapidly available glucose in foods: an in vitro measurement that reflects the glycemic response. in The American journal of clinical nutrition

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Fewtrell MS (1999) Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet. in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

 
Description IOTF BMI cutoffs systematic review citations
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
Impact My paper (Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity: international survey. BMJ 2000;320:1240-3) gave a set of BMI cut-offs by age and sex to define overweight and obesity in children internationally. It has since been cited >3500 times, and Web of Science classifies 102 of these citations since 2006 as 'reviews'. A few highly cited examples of these reviews are (in November 2011): Title: Interventions for treating obesity in children Author(s): Luttikhuis HO, Baur L, Jansen H, et al. Source: COCHRANE DATABASE OF SYSTEMATIC REVIEWS Issue: 1 Article Number: CD001872 Published: 2009 Times Cited: 74 Title: Epidemiology of Obesity in the Western Hemisphere Author(s): Ford ES, Mokdad AH Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Volume: 93 Issue: 11 Pages: S1-S8 Supplement: Suppl. 1 Published: NOV 2008 Times Cited: 58 Title: Socioeconomic status and adiposity in childhood: A systematic review of cross-sectional studies 1990-2005 Author(s): Shrewsbury V, Wardle J Source: OBESITY Volume: 16 Issue: 2 Pages: 275-284 Published: FEB 2008 Times Cited: 95 Title: Assessment of child and adolescent overweight and obesity Author(s): Krebs NF, Himes JH, Jacobson D, et al. Source: PEDIATRICS Volume: 120 Pages: S193-S228 Supplement: Suppl. S Published: DEC 2007 Times Cited: 127 Title: Body mass index in children and adolescents: considerations for population-based applications Author(s): Must A, Anderson SE Source: INTERNATIONAL JOURNAL OF OBESITY Volume: 30 Issue: 4 Pages: 590-594 Published: APR 2006 Times Cited: 28
 
Description Irish growth charts
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact discussion about changing the Irish national growth charts to include WHO, following the UK model.
 
Description LMS method applications
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact My LMS method (Cole TJ, Green PJ. 1992. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 11:1305-1319) has been cited 472 times to date, 278 times since 2006. It allows researchers to derive age-related reference ranges for measurements in children, such as height and weight growth charts, blood pressure centiles etc. The 278 citations show that the method has been applied, often using my software LMSchartmaker (licensed via MRC), in many countries and organisations e.g. USA, WHO, Germany, Italy, Netherlands, Norway, Denmark, Saudi Arabia, Kuwait, Bulgaria, Turkey, Greece, Poland, India and Argentina. Growth charts for the last three countries have been published in 2009/10 with Cole or Pan as co-authors. The measurements to which the method has been applied include anthropometry (weight, height, arm circumference, % body fat etc), blood pressure, heart rate, lung function, aerobic fitness, etc, for children at all ages from fetus through neonatal, infant, preschool and school age to adolescent.
 
Description SACN BMI cutoffs
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact The Department of Health uses BMI cutoffs for classifying overweight and obesity in children. The Standing Advisory Committee on Nutrition met to discuss changing the cutoffs. Another meeting has been called to finalise the decision, which will affect all national reporting of child obesity.
 
Description SACN growth charts
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact SACN published its report recommending that WHO charts be introduced to the UK. The new charts have since been designed, produced and launched nationally (May 2009).
 
Description UK-WHO growth charts
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact I am a member of the Royal College of Paediatrics and Child Health expert group funded by the English Department of Health to design the new UK-WHO growth charts, which were launched nationally in May 2009. Some hundreds of thousands of printed growth charts are used in primary care, secondary care and by parents of young children. The expert group has continued to meet in 2011/12 to develop growth charts for the age group 4-18 years. This activity also appears under collaborations.
 
Description UK90 BMI centiles
Geographic Reach National 
Policy Influence Type Citation in systematic reviews
Impact My paper (Cole TJ, Freeman JV, Preece MA. Body mass index reference curves for the UK, 1990. Arch Dis Child 1995;73:25-9) published BMI centiles for the UK and has been used since 1995 for national BMI assessment and screening. It has been cited 690 times to date, and Web of Science categorises 27 of these citations since 2006 as 'reviews'. Some highly cited examples of such review citations are as follows: Title: Body mass index in children and adolescents: considerations for population-based applications Author(s): Must A, Anderson SE Source: INTERNATIONAL JOURNAL OF OBESITY Volume: 30 Issue: 4 Pages: 590-594 Published: APR 2006 Times Cited: 24 Title: The evolution of human fatness and susceptibility to obesity: an ethological approach Author(s): Wells JCK Source: BIOLOGICAL REVIEWS Volume: 81 Issue: 2 Pages: 183-205 Published: MAY 2006 Times Cited: 30 Title: Metabolic risk-factor clustering estimation in children: to draw a line across pediatric metabolic syndrome Author(s): Brambilla P, Lissau I, Flodmark CE, et al. Source: INTERNATIONAL JOURNAL OF OBESITY Volume: 31 Issue: 4 Pages: 591-600 Published: APR 2007 Times Cited: 23 Title: Tracking of childhood overweight into adulthood: a systematic review of the literature Author(s): Singh AS, Mulder C, Twisk JWR, et al. Source: OBESITY REVIEWS Volume: 9 Issue: 5 Pages: 474-488 Published: SEP 2008 Times Cited: 41
 
Description WHO growth velocity
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
 
Description Buchan 
Organisation University of Manchester
Department School of Medicine Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution contribution of data and joint authorship
Impact publication: 16880777
 
Description GOSH 
Organisation Great Ormond Street Hospital (GOSH)
Country United Kingdom 
Sector Hospitals 
PI Contribution advice on aspects of growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 19875994 16552412 19183310 18043501 16986993 16936560
 
Description Jackson 
Organisation University of East Anglia
Department School of Medicine UEA
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution contribution of data and joint authorship
Impact publication: 16905566
 
Description LSHTM 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Epidemiology and Population Health
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 16306313 17200989 19564879 16570089
 
Description MRC CECH 
Organisation University College London
Department MRC Centre for Epidemiology for Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 18469281 16984935 19019884 17637703 19789171 18801795 18089633 18403500 19085539 16801947
 
Description MRC HNR 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 19594476 18541591 16522914 22990031
 
Description MRC Nutrition ICH 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on aspects of growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 17429924 17667912 18239656 16770333 16894361 17179023 17209191 23076617 22580078 27604768
 
Description Martin 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publication: 17301110
 
Description Portex 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 19574442 19065626 17197485 18006882 20351026 20817707 23045209 22743675 22474159 22183491 25254426 25700391 25837028 26493801 27831907
 
Description Rudolf 
Organisation University of Leeds
Department Faculty of Medicine and Health
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publication: 17763011 22529106
 
Description SCHARR 
Organisation University of Sheffield
Department School of Health and Related Research (ScHARR)
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth
Collaborator Contribution joint authorship
Impact publications: 16724479 16551784
 
Description Soc Med Bristol 
Organisation University of Bristol
Department School of Social and Community Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 16344844 16720666
 
Description UCL Epidemiology 
Organisation University College London
Department Institute of Epidemiology and Health Care
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and joint authorship
Impact publications: 19884892 16679329
 
Description US CDC 
Organisation Centers for Disease Control and Prevention (CDC)
Country United States 
Sector Public 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution joint authorship
Impact publication: 17591624
 
Description Wang 
Organisation Johns Hopkins University
Department Department of International Health
Country United States 
Sector Academic/University 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution joint authorship
Impact publication: 17361655
 
Title International BMI cut-offs 
Description A set of cut-off values for children's BMI by age and sex, identifying obesity, overweight, and thinness. They were described in BMJ articles in 2000 and 2007. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Market authorisation
Year Development Stage Completed 2007
Development Status Closed
Impact The international cut-offs have been widely cited (5000+ Web of Science citations, Oct 2014) and are regularly mentioned in systematic reviews of child obesity prevention and treatment. 
 
Title LMSchartmaker software 
Description The LMS method summarises the distribution of the measurement (e.g. weight) as it changes with age, in terms of the median, coefficient of variation and skewness (based on a Box-Cox power). The three quantities are modelled as cubic spline curves in age, and so summarise the whole distribution as it changes with age. The LMSchartmaker software makes this statistical analysis accessible to non-statisticians to construct growth centile charts. It is available on the web as a Windows program in two forms, Light (free) and Pro (paid for). The software has been continually developed since before 2006, but there have been notable improvements since then. 
Type Of Technology Software 
Impact The LMSchartmaker software is widely used for growth chart construction. The underlying statistical theory paper (Cole & Green, 1992) has been cited some 400 times, and the method has been used for national growth references in many countries including the UK, US, Netherlands and World Health Organization. Downloads of the Light version are not recorded, but the Pro version pays a royalty to the MRC under an agreement with Harlow Printing Ltd, who host the download site. 
 
Title LMSgrowth Excel add-in 
Description The LMSgrowth add-in allows users to manipulate growth references and growth charts fitted by the LMS method (e.g. using my LMSchartmaker software), allowing children's heights and weights etc to be converted to centiles and z-scores. 
Type Of Technology Software 
Impact The software is a free download from a website hosted by Harlow Printing, a company that sells growth charts. It is used by paediatric health professionals very widely in the UK, as a way to handle growth data as collected either in general practice, growth clinics or in research. 
 
Description Breastfeeding Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 300 health visitors and midwives at the UNICEF UK Baby Friendly Initiative Annual Conference heard me talk on the WHO growth charts: implications for practice in the UK

lots of interest - the first they had heard of the new charts, based on breastfed infants
Year(s) Of Engagement Activity 2006
 
Description Neonatal Update 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact In 2006 gave a talk to ~100 paediatricians attending the annual Neonatal Update conference about how to use growth charts.

In 2011 gave another talk, on the subject of my SITAR growth curve analysis for developing longitudinal growth curve charts for very preterm infants.

Both talks were very well received and generated a lot of interest and discussion.
Year(s) Of Engagement Activity 2006,2011
 
Description Singapore 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I was invited to Singapore to develop new growth charts there, and at the end of the week I gave two talks describing the charts - one for health professionals and the other for parents and the public. Both audiences were several hundred strong.

I left the country immediately afterwards, so can't say what impact I made.
Year(s) Of Engagement Activity 2007