Article Text

Download PDFPDF

Original research
INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study
  1. Michelle Fernandes1,2,
  2. José Villar2,3,
  3. Alan Stein4,
  4. Eleonora Staines Urias2,
  5. Cutberto Garza5,
  6. Cesar G Victora6,
  7. Fernando C Barros7,
  8. Enrico Bertino8,
  9. Manorama Purwar9,
  10. Maria Carvalho10,
  11. Francesca Giuliani11,
  12. Katharina Wulff12,13,
  13. Amina A Abubakar14,
  14. Michael Kihara15,
  15. Leila Cheikh Ismail16,
  16. Luis Aranzeta17,
  17. Elaine Albernaz18,
  18. Naina Kunnawar9,
  19. Paola Di Nicola11,
  20. Roseline Ochieng10,
  21. Tamsin Sandells2,
  22. Sandy Savini2,
  23. Sophie Temple2,
  24. Elizabeth Murray4,
  25. Eric O Ohuma2,19,
  26. Michael G Gravett20,
  27. Ruyan Pang21,
  28. Yasmine A Jaffer22,
  29. Julia Alison Noble23,
  30. Adele Winsey2,
  31. Ann Lambert2,
  32. Aris T Papageorghiou2,3,
  33. Zulfiqar Bhutta24,
  34. Stephen Kennedy2,3
  1. 1Faculty of Medicine, Department of Paediatrics, University of Southampton, Southampton, UK
  2. 2Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK
  3. 3Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, Oxfordshire, UK
  4. 4Section of Child and Adolescent Psychiatry, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
  5. 5Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
  6. 6Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil
  7. 7Post-Graduate Program in Health and Behavior, Universidade Catolica de Pelotas, Pelotas, Rio Grande do Sul, Brazil
  8. 8Dipartimento di Scienze Pediatriche e dell’ Adolescenza, SCDU Neonatologia, Universita di Torino, Torino, Piemonte, Italy
  9. 9Nagpur INTERGROWTH-21st Research Centre, Ketkar Hospital, Nagpur, India
  10. 10Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya
  11. 11Ospedale Infantile Regina Margherita, Sant’Anna Citta della Salute e della Scienza di Torino, Torino, Piemonte, Italy
  12. 12Department of Radiation Sciences, Umeå University, Umeå, Sweden
  13. 13Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden
  14. 14Neurosciences Unit, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
  15. 15Department of Psychology, United States International University, Nairobi, Kenya
  16. 16College of Health Sciences, University of Sharjah, Sharjah, UAE
  17. 17Centro de Tecnologıa e Innovacion, Mexico City, Mexico
  18. 18Faculty of Medicine, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil
  19. 19Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK
  20. 20Departments of Obstetrics and Gynecology and of Global Health, University of Washington, Seattle, Washington, USA
  21. 21School of Public Health, Peking University, Beijing, China
  22. 22Department of Family & Community Health, Ministry of Health, Muscat, Oman
  23. 23Department of Engineering Science, University of Oxford, Oxford, UK
  24. 24Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
  1. Correspondence to Dr Michelle Fernandes; michelle.fernandes{at}


Objectives To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project.

Design Population-based cohort study, the INTERGROWTH-21st Project.

Setting Brazil, India, Italy, Kenya and the UK.

Participants 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes.

Primary measures Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones.

Results Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA’s cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA’s negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22–30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges.

Conclusions From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes.

  • community child health
  • developmental neurology & neurodisability
  • paediatrics
  • epidemiology

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

View Full Text

Statistics from


  • Twitter @Dr_MCFernandes

  • Contributors JV and SK conceptualised and designed the INTERGROWTH-21st Project. MF, JV, SK, AS, LA, AAA, MK, FG and KW designed and developed the FGLS neurodevelopmental follow-up and the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA). JV, SK, CGV, FCB, ZB, CG, EB, ATP, MGG, RP, YAJ, LCI and EB were responsible for the implementation all aspects of the INTERGROWTH-21st Project. MF, JV, SK and LCI coordinated the implementation of the neurodevelopmental follow-up. MF, LCI, FCB, EA, PDN, EB, FG, MP, NK, RO, MC, TS, ST, EM, AL and AW were responsible for site-based training and data collection. JV, SK, ESU, EOO and MF were responsible for data management. MF, JV, ESU, EOO and SK had access to the Project’s data; JV, ESU, MF, SK and EOO were responsible for the statistical analysis. MF and JV wrote the report with input from all the other authors. All authors reviewed and approved the final manuscript. SK and JV are responsible for the overall content as guarantors. The guarantors accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding This work was supported by a grant from the Bill & Melinda Gates Foundation to the University of Oxford, Oxford, UK (Grant ID# 49038). MF is supported by an Academic Clinical Fellowship in Paediatrics from the National Institute for Health Research, UK to the University of Southampton. ATP is supported by the National Institute for Health Research Oxford Biomedical Research Centre.

  • Disclaimer The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The INTERGROWTH-21st Project was approved by the research ethics committees of the Universidade Federal de Pelotas, Faculdade de Medicina comitê de ética em pesquisa (Ref: OF.051/09), the Indian Ministry of Health and Family Welfare and the Institutional Ethics Committee, Ketkar Hospital, Nagpur (Ref: 5/7/314/2008-RHN); Servizio Sanitario Nazionale – Regione Piemonte, Aziende Ospedaliere OIRM/S.Anna, Oridine Mauriziano di Torino, Comitato Etico Interaziendale (Ref: G9947/CEI/ C.27.2); the Aga Khan University Health Research Ethics Committee, Aga Khan University, Nairobi, Kenya (Ref: AKU- 09-106), and the Oxfordshire Research Ethics Committee ‘C’, UK (Ref: 08/H0606/139).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Extra data are available by emailing

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.