M.O. Savaage, L.B. Johnston, C. Camacho-Hubner, P,G. Chatelain, K.A. Woods, J-L Chaussain, K. Ong, D.B. Dunger, A.J.L. Clark, K. Albertsson-Wikland, J. Dahlgren, F. DeZegher

St Bartholomew’s Hospital, London, UK, Growth Research Center, Gothenburg Sweden, Hospital, Debrousse, Lyon, Hospital Saint-Vincent-de-Paul, Paris, France, Addenbroke’s Hospital, Cambridge, UK, University Hospital, Leuven, Belgium


The control of fetal and post-natal growth is related to secretion and action of GH and IGF-I. In fetal life IGF-I , regulated by nutrition, plays a key role in growth. The role of GH is more subtle. In post-natal life the actions of GH and IGF-I maintain linear growth, permitting catch-up growth, permitting catch-up growth of most IUGR infants. Genetic defects of GH and IGF-I secretion and action have helped understanding of fetal growth.


Mutations in the human IGF-I gene and the IGF-I receptor gene are associated with severe IUGR. Whereas those of the GH receptor are not linked to IUGR, although a slight reduction in birth length SDS (mean –1,01,-5.17to +2.55) was reported in 82 patients with GH insensitivity syndrome. Epidemiological studies have shown that birth size and post-natal growth are strongly influenced by genetic factors. In a candidate gene study in 116 short IUGR children, intronic and micro-satellite markers for the IGF-I gene showed statistical association (p=0.0009) with the short IYGR phenotype, suggesting that the IGF-I gene may influence growth in short IUGR children.


GH and IGF- resistance has been suggested in IUGR children. In cohorts of IUGR and idiopathic short stature (ISS) children treated with hGH 1.2IU/Kg/week, IGF-I levels were higher in the IHGR subjects when both groups had comparable neight velocity values. Measurement of insulin, GH and IGF-I levels in 16 short IUGR children compared to ISS controls showed higher fasting insulin, lower insulin sensitivity (HOMA) and higher GH and IGF-I levels supporting resistance to GH and IGF-I. This may also contribute to insulin resistance in these subjects.