A randomised controlled trial evaluating IGF-I titration in contrast to current GH dosing strategies in children born Small for Gestational Age (NESGAS).

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Background: Short children born small for gestational age (SGA) are treated with growth hormone (GH) dose based on body size, but treatment may lead to high levels of IGF-I. The objective was to evaluate IGF-I titration of GH dose in contrast to current dosing strategies. Methods: In the North European Small for gestational age study (NESGAS) 92 short pre-pubertal children born SGA were randomised after one year of high dose GH treatment (67µg/kg/day) to three different regimens: high-dose (67µg/kg/day), low-dose (35µg/kg/day) or IGF-I titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF-I titration group (38µg/kg/day, SD 0.019) and the low-dose group (35µg/kg/day, SD 0.002) (P=0•46), but there was a wide variation in the IGF-I titration group (range 10-80µg/kg/day). The IGF-I titration group had significantly lower height gain (0.17SDS, SD 0.18) during the second year of the randomised trial compared to the high-dose group (0.46SDS, SD 0.25) but not significantly lower than the low-dose group (0.23SDS, SD 0.15) (p=0.17). The IGF-I titration group had lower IGF-I levels after two years of the trial (mean 1.16, SD 1.24) compared to both the low-dose (mean 1.76, SD 1.48) and the high-dose (mean 2.97, SD 1.63) groups. Conclusion: IGF-I titration of GH dose in SGA children proved less effective than current dosing strategies. IGF-I titration resulted in physiological IGF-I levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF-I resistance and highlights the heterogeneity of short SGA children.


  • Rikke Beck Jensen
  • Ajay Thankamony
  • Susan M O'Connell
  • Jeremy M W Kirk
  • Malcolm Donaldson
  • Sten Ivarsson
  • Olle Soder
  • Edna Roche
  • Hilary Hoey
  • David P Dunger
  • Anders Juul
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)509-518
JournalEuropean Journal of Endocrinology
Issue number4
Publication statusPublished - 2014
Publication categoryResearch