Short Stature: Comparison of WHO and National Growth Standards/References for Height

PLoS One. 2016 Jun 9;11(6):e0157277. doi: 10.1371/journal.pone.0157277. eCollection 2016.

Abstract

The use of appropriate growth standards/references is of significant clinical importance in assessing the height of children with short stature as it may determine eligibility for appropriate therapy. The aim of this study was to determine the impact of using World Health Organization (WHO) instead of national growth standards/references on height assessment in short children. Data were collected from routine clinical practice (1998-2014) from nine European countries that have available national growth references and were enrolled in NordiNet® International Outcome Study (IOS) (NCT00960128), a large-scale, non-interventional, multinational study. The patient cohort consisted of 5996 short pediatric patients diagnosed with growth hormone deficiency (GHD), Turner syndrome (TS) or born small for gestational age (SGA). The proportions of children with baseline height standard deviation score (SDS) below clinical cut-off values (-2 SDS for GHD and TS; -2.5 SDS for SGA) based on national growth references and WHO growth standards/references were compared for children aged <5 years and children aged ≥5 years. In seven of the countries evaluated, significantly fewer children aged ≥5 years with GHD (22%; P<0.0001), TS (21%; P<0.0001) or born SGA (32%; P<0.0001) had height below clinical cut-off values using WHO growth references vs. national references. Likewise, among children aged <5 years in the pooled analysis of the same seven countries, a significantly lower proportion of children with GHD (8%; P<0.0001), TS (12%; P = 0.0003) or born SGA (12%; P<0.0001) had height below clinical cut-off values using WHO growth standards vs. national references. In conclusion, in NordiNet® IOS the number of patients misclassified using WHO growth standards/references was significantly higher than with national references. This study highlights that, although no growth reference has 100% sensitivity for identifying growth disorders, the most recent national or regional growth charts may offer the most appropriate tool for monitoring childhood growth in Europe.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Body Height*
  • Child
  • Child Development*
  • Child, Preschool
  • Europe
  • Female
  • Growth Disorders* / pathology
  • Growth Disorders* / physiopathology
  • Human Growth Hormone / deficiency*
  • Humans
  • Male
  • Turner Syndrome* / pathology
  • Turner Syndrome* / physiopathology

Substances

  • Human Growth Hormone

Grants and funding

NordiNet® IOS is funded by Novo Nordisk Healthcare AG, Zurich, Switzerland. Novo Nordisk is responsible for conducting the study and performing the data analysis. The decision to publish, results’ interpretation and manuscript development is the outcome of Novo Nordisk collaboration with the members of the International Study Committee (ISC) who are co-authoring this manuscript. The NordiNet® IOS ISC acts as the custodian of the database and provides governance with respect to the data analyses and the publication plan of the study. Writing and editorial assistance from Watermeadow Medical was funded by Novo Nordisk Healthcare AG, Zurich, Switzerland.