Sensitivity to IGF-I in short children born small for gestational age.

About 5% of newborns are classified as small for gestational age (SGA) and of these, 10-15% do not catch up in growth by 2 yr of age. In addition to genetic mutations in the GH-IGF-IGFBP axis, environmental factors may re-program growth during fetal development leading to altered hormone sensitivity. This review summarizes the importance of GH treatment in SGA children. Although GH dose is the most relevant factor for growth response in children born SGA, higher GH doses are needed in SGA subjects to induce a growth response comparable to GH deficient (GHD) patients. Therapeutic difficulties possibly arise from the impaired hormone sensitivity along the GH-IGF-IGFBP axis. Indeed, several observations point towards impaired sensitivity to hormones involved in the GH-IGF-IGFBP axis in children born SGA. The inability to classify SGA patients according to the relative GH and IGF-I concentrations is probably due to the large variation in hormone sensitivity patterns in patients with SGA. Simple laboratory tests need to be established that directly quantify sensitivity to parameters in the GH-IGF-IGFBP axis, such as IGF-I. Adequate additional therapies could in future result in positive effects on co-morbidities associated with IGF-I insensitivity in SGA children in addition to height gain.