Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial

J Clin Endocrinol Metab. 1999 Sep;84(9):3064-70. doi: 10.1210/jcem.84.9.5942.


The growth-promoting effect of continuous GH treatment was evaluated over 5 yr in 79 children with short stature (height SD score, less than -1.88) born small for gestational age (SGA; birth length SD score, less than -1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage groups (3 vs. 6 IU/m2 body surface-day). GH deficiency was not an exclusion criterium. After 5 yr of GH treatment almost every child had reached a height well within the normal range for healthy Dutch children and in the range of their target height SD score. Only in children who remained prepubertal during the study period was the 5-yr increase in height SD score (HSDS) for chronological age significantly higher in the study group receiving 6 compared to 3 IU GH/m2 x day. Remarkably, the 5-yr increment in HSDS for chronological age was not related to spontaneous GH secretion, maximum GH levels after provocation, or baseline insulin-like growth factor I levels. GH treatment was associated with an acceleration of bone maturation regardless of the GH dose given. The HSDS for bone age and predicted adult height increased significantly. GH treatment was well tolerated. In conclusion, our 5-yr data show that long term continuous GH treatment at a dose of 3 or 6 IU/m2 x day in short children born SGA results in a normalization of height during childhood followed by growth along the target height percentile.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Body Height*
  • Body Mass Index
  • Bone Development
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Growth
  • Human Growth Hormone / administration & dosage*
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / blood
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Reference Values


  • Insulin-Like Growth Factor Binding Protein 3
  • Human Growth Hormone
  • Insulin-Like Growth Factor I