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.