The SITAR method of growth curve analysis for growth assessment in translational medicine and life course epidemiology

Lead Research Organisation: University College London
Department Name: Institute of Child Health

Abstract

The pattern of growth in individual children, as represented by their growth curve of successive measurements (e.g. weight or height) plotted against age, may be informative about their circumstances at earlier ages, or conversely it may predict their risk of disease later in life, for example heart disease, stroke or type 2 diabetes. To investigate this it is necessary to summarise the shape of each individual's growth curve in a simple way, so that its shape can be related to their earlier or later experiences. The SITAR method of growth curve analysis is a novel approach that does just this - it summarises each individual growth curve in just three numbers, reflecting respectively their size (i.e. tall or short, heavy or light, as compared to others), their growth tempo (i.e. whether they are relatively mature or delayed in their timing of growth, e.g. age of menarche in girls), and velocity (how fast they are growing compared to others, e.g. in puberty). In addition SITAR estimates a smooth average growth curve against which each individual's growth can be compared. The surprising thing is that this model explains nearly all of the variability in growth between individuals, so that their size, tempo and velocity can be viewed as a complete summary of their growth pattern. Put another way, when adjusted for size, tempo and velocity all their growth curves are the same. It is then simple to relate the values of size, tempo and velocity in individuals to their earlier or later experiences, and to look for links between them.

Technical Summary

The SITAR method of growth curve analysis summarises individual growth patterns of e.g height or weight in three parameters (size, tempo and velocity) that are estimated as subject random effects, plus a cubic spline estimate of the average growth curve. It explains over 95% of the age-specific variance in the outcome measure, and as such is an effective summary of individual growth patterns. The subject-specific random effects can then be related to earlier growth-affecting exposures or later health outcomes. Thus it is relevant in translational medicine and life course epidemiology. The aims of the project are (i) to further develop the SITAR methodology, (ii) to apply it to a series of existing growth studies, and (iii) to develop a SITAR software library in the R statistical language for its wider dissemination. Methodological developments will include exploring P-splines as an alternative to B-splines for the average curve, and deriving standard errors for the random effects. The application studies are collaborations involving a mix of observational and experimental data, covering height, weight and BMI in infancy, puberty and all childhood, and they include the British 1946, 1958, ALSPAC and Millennium birth cohorts. The R library will enable other statisticians and epidemiologists to apply the method relatively simply.

SITAR can also be applied to cross-sectionally based median curves of say height versus age, as used in growth charts. SITAR allows such median curves from different growth references to be superimposed, which is useful for merging charts and for understanding differences in the underlying reference populations.

Planned Impact

Who will benefit from this research, and how?

o Academia
All researchers, national and international, interested in the analysis of longitudinal growth will find SITAR of interest, as it will allow them to summarise individual growth patterns in a simple way and then link the pattern to other aspects of the individual's health and lifestyle.

o Public Sector
National policy makers concerned with the high and rising levels of childhood obesity will want to explore the idea from SITAR that overweight children have an advanced maturational age, and look for lifestyle interventions that might counteract this accelerated age pattern.

o Business/Industry
The international pharmaceutical industry will value a statistical tool that simplifies and sharpens the assessment of growth-affecting treatments. SITAR's efficient use of data will mean that clinical trials involving growth outcomes need not be as large as before, and hence may reach conclusions more quickly and certainly more cheaply. This in turn should make cheaper the development of new growth-affecting drugs.

o Parents and children
Parents and children worldwide will benefit from improved growth assessment through the development of more effective evidence-based growth charts, particularly in puberty. Improvements in the assessment and treatment of obesity will impact on the quality of life of children now and on the adults they will become.

Publications

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Cole T (2015) Too many digits: the presentation of numerical data in Archives of Disease in Childhood

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Cole T (2012) Designing the new UK-WHO growth charts to enhance assessment of growth around birth in Archives of Disease in Childhood - Fetal and Neonatal Edition

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Cole T (2012) People smugglers, statistics and bone age in Significance

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Cole TJ (2014) Response to: Human linear growth trajectory defined. in American journal of human biology : the official journal of the Human Biology Council

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Cole TJ (2014) Birth weight and longitudinal growth in infants born below 32 weeks' gestation: a UK population study. in Archives of disease in childhood. Fetal and neonatal edition

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Cole TJ (2012) The development of growth references and growth charts. in Annals of human biology

 
Description Australian policy on age assessment in people smuggling cases
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact Under Engagement Activities I describe the use of bone age based on hand-wrist x-rays to test whether alleged people smugglers in Australia are under or over 18 years of age. Further I describe my role in the Australian Government's recent decision to stop using bone age for this purpose. This impact was made via the expert witness evidence I gave in 11 Australian court cases of people smuggling, and my evidence to a formal Inquiry by the Australian Human Rights Commission which reported on this issue of forensic age assessment. My evidence was that bone age is not fit for purpose for deciding whether or not individuals are adult or minor, and that it should not be used. The main impact of the Australian policy change will be improvement in the quality of life of Indonesian fishermen charged with people smuggling who say they are aged under 18. They are less likely to be jailed for months before a decision is taken on their putative age, and the process for deciding their age should be more transparent.
 
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 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 MRC Research Grant
Amount £72,596 (GBP)
Funding ID MR/M012069/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2015 
End 02/2018
 
Title sitar library 
Description a library package written in R to fit my sitar growth curve model. It is available free to download from CRAN (the Comprehensive R Archive Network) and the source code is available free at Github (URL below). 
Type Of Material Computer model/algorithm 
Year Produced 2013 
Provided To Others? Yes  
Impact The sitar package has been used by several research groups who have downloaded it from CRAN. The sitar model has been the basis for my research for the past few years, and it has resulted in 19 publications and 78 citations (as of March 2019). 
URL https://github.com/statist7/sitar
 
Description Charlotte Wright 
Organisation University of Glasgow
Department Maternal and Child Health Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution data and statistical analysis
Collaborator Contribution clinical expertise
Impact 26883079 29998577
Start Year 2011
 
Description Crozier 
Organisation University of Southampton
Department MRC Lifecourse Epidemiology Unit
Country United Kingdom 
Sector Public 
PI Contribution advice on growth modelling
Collaborator Contribution provision of data and shared authorship
Impact 30719940
Start Year 2011
 
Description Donaldson 
Organisation Royal Hospital for Children
Country United Kingdom 
Sector Hospitals 
PI Contribution advice on growth modelling
Collaborator Contribution provision of data and shared authorship
Impact 20647267, 21493672
 
Description Donaldson 
Organisation University of Glasgow
Department Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth modelling
Collaborator Contribution provision of data and shared authorship
Impact 20647267, 21493672
 
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 Centre of Epidemiology for Child Health 
Organisation University College London
Department MRC Centre for Epidemiology for Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Lead on the statistical methodology theme of the Centre. Joint publication with other members of the Centre. Participation in Centre scientific and academic seminars, workshops, symposia and masterclasses and multi-disciplinary team working.
Collaborator Contribution Statistical, epidemiological and IT expertise from other members of the Centre.• Access to a critical mass of epidemiological and statistical expertise applied to children's health creating a positive working environment that contributes to researcher capacity, scientific excellence, methodological expertise and impact in this field. The mission of the MRC Centre of Epidemiology for Child Health is to improve the health and well being of children by conducting, and contributing to the application of, high quality interdisciplinary research. The MRC Centre adds value by: exploiting opportunities for electronic health record linkage; developing and applying advanced statistical methods; capacity building in genetic epidemiology; and developing approaches to policy research in child health. • Provision of Epilab: The epiLab is an advanced computing environment and data management service that has been developed at the MRC Centre to support researchers through all aspects of the research data management life-cycle. The service provides core data storage and backup provision in conjunction with a virtualised desktop and backend-server infrastructure, designed to provide high levels of resilience and information security. Additional services provide users with tools, training and assistance with data transfer, metadata management, data collection, archival and destruction and pseudonymisation.
Impact Publications, other collaborations and partnerships, influence on policy and practice, networking opportunities. Joint papers are listed under Other-MRC in the Contribution section.
Start Year 2007
 
Description MRC HNR 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Group
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 LHA 
Organisation University College London
Department MRC Unit for Lifelong Health and Ageing
Country United Kingdom 
Sector Public 
PI Contribution advice on growth and statistical analysis
Collaborator Contribution provision of data and other analyss
Impact publications: 27466311 27401728
Start Year 2013
 
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 Modi 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution advice on growth modelling
Collaborator Contribution contribution of data and shared authorship
Impact 23934365
Start Year 2009
 
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 RCPCH growth chart expert group 
Organisation Royal College of Paediatrics and Child Health (RCPCH)
Country United Kingdom 
Sector Multiple 
PI Contribution I as a member of the expert group have attended meetings discussing the design of the charts, and been involved in publications, presentations and training about the new materials.
Collaborator Contribution There have been several presentations to the RCPCH conference and subsequent publications arising from the work of the group, about the design of new growth charts for the UK. In addition the group has developed and had published the UK-WHO growth charts, now universally used in the UK. I have continued collaborating with Prof Charlotte Wright, chair of the expert group, and have set up a separate entry for her.
Impact The main outcome has been the new UK-WHO age 0-4 year charts. A copy is given to all new parents, totalling some 600k copies per year. Further outcomes have been RCPCH presentations and peer-reviewed publications: 20231247, 21175302, 21398325, 21767107.
Start Year 2008
 
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 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
 
Title Growth chart aids 
Description Two new forms of growth charts incorporated into the UK-WHO growth charts. The first predicts a child's adult height, from as young as 2 years, and the second uses a lookup to provide a child's BMI centile without having to calculate BMI or use BMI charts. Both are incorporated in the new UK-WHO charts. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Market authorisation
Year Development Stage Completed 2009
Development Status Closed
Impact For the first time children and their parents will have a good idea how tall the child will be. Also the assessment of overweight is greatly simplified with the BMI look-up. The work has been published as 21767107, and the BMJ has published an editorial commenting on the paper. 
 
Title sitar library 
Description Software to fit the SITAR method to growth curves, submitted as the sitar package to the Comprehensive R Archive Network (CRAN). 
Type Of Technology Software 
Year Produced 2013 
Open Source License? Yes  
Impact The availability of the open source software within R, the widely used free statistical software environment, has simplified its dissemination and encouraged others to try the method out. 
URL http://cran.r-project.org/web/packages/sitar/index.html
 
Description 567 CapeTalk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I was interviewed by the South African radio station 567 CapeTalk to discuss a new index that had been proposed by Professor Trefethen to improve on the body mass index.

nothing obvious
Year(s) Of Engagement Activity 2013
 
Description BBC Radio 4 More or Less 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact In 2011 I spoke on the BBC Radio 4 programme More or Less, two successive weeks, about predicting a child's adult height from their current height.

In 2013 I discussed a new index that had been proposed by Professor Trefethen to improve on the body mass index.

In 2015 I was asked the question "Are tall people more likely to get cancer?" (URL below)

Several friends and colleagues remarked that they'd heard the programme.
Year(s) Of Engagement Activity 2011,2013,2015
URL http://www.bbc.co.uk/programmes/p0343hhk
 
Description BBC World Football 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact I was interviewed by the BBC World Service radio programme World Football about the method used by FIFA to check for over-age players in Under-17 World Cup football matches.

nothing obvious yet, though I criticised FIFA's method as being unfit for purpose.
Year(s) Of Engagement Activity 2013
 
Description Eighteen SITAR seminars 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Since 2009 I have given 18 invited seminars describing my SITAR growth curve analysis, which is the subject of my MRC project grant. The audiences, generally made up of statisticians and epidemiologists, have ranged from 10 to 50 or more, and have consistently generated questions and discussion afterwards.

The seminars took place in the following places: University of Buenos Aires, Argentina; British Society for Paediatric Endocrinology and Diabetes (BSPED) conference, Reading; University of Chapel Hill, NC USA; UCL, Statistical Science; Social Medicine, University of Bristol; Royal Statistical Society life course conference, Leeds (twice); Society for Longitudinal and Lifecourse Studies conference, Cambridge; Penn State University, PA USA; London School of Hygiene and Tropical Medicine (twice); Imperial College, London; University of Rotterdam, Netherlands; French Region International Biometric Society workshop, Bordeaux France; Centre for Advanced Studies University of Munich workshop, Germany; MRC Lifelong Health and Ageing Unit workshop, London; UCL Institute of Child Health symposium; Austrian Region International Biometric Society conference, Dornbirn Austria.

The seminars have raised interest in and awareness of my SITAR method, leading to further invitations to talk about it.
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
 
Description Expert witness in age assessment hearings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I gave evidence as an expert witness about forensic age assessment, to the Court of Session in Edinburgh, via videolink to the District Court in Perth Australia, and by phone to the Magistrates Court in Melbourne Australia. I also provided expert witness reports to these cases plus a further nine in other Australian courts in Brisbane, Perth and Sydney.

All eleven Australian cases involved Indonesian fishermen accused of people smuggling, where if found guilty and aged over 18 the mandatory sentence is 5 years in jail. But if under 18 they are repatriated. In my evidence I argued that the wrist x-ray technique used for assessing their age is not fit for purpose.

My evidence caused nine of the eleven Australian cases to be dropped, with the accused being repatriated and a longstanding prosecution witness being discredited.

The URL above covers the Australian Human Rights Commission's "Inquiry into the treatment of individuals suspected of people smuggling offences who say that they are children", to which I gave evidence that is reported extensively in Chapter 2 of the AHRC report "An Age of Uncertainty". The report was undoubtedly a key factor in the Australian government's subsequent decision to no longer use bone age based on hand-wrist x-rays to assess chronological age.

I also wrote an article describing one of the court cases -
doi 10.1111/j.1740-9713.2012.00568.x
Year(s) Of Engagement Activity 2011
URL http://www.humanrights.gov.au/age-assessment-people-smuggling-cases-inquiry-treatment-individuals-su...
 
Description MRC@UCL Centenary Science Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact For the MRC@UCL Centenary Science Fair held in UCL on 29 June 2013, I ran a stall as part of the MRC Centre of Epidemiology for Child Health where I measured the heights of 111 children, plotted them on a large poster-size growth chart, and predicted their adult height.

Publicity for the MRC. About 500 visitors attended the Fair on the day, so I got to measure over a fifth of them, which was probably most of the children attending. Lots of interest in children's final heights.
Year(s) Of Engagement Activity 2013
 
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 The Voice of Russia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I was invited by The Voice of Russia to discuss a new index that had been proposed by Professor Trefethen to improve on the body mass index. The audience was radio and online.

nothing obvious
Year(s) Of Engagement Activity 2013
 
Description Young Fabians 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact 9 people attended a policy meeting of the Young Fabians, held in the Houses of Parliament, to provide advice to the Labour Party for its 2015 election manifesto. The topic was child obesity, where I was one of three invited experts who introduced the discussion.

None yet, though it may in due course affect the Labour manifesto.
Year(s) Of Engagement Activity 2013