Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease

Daniel Bernstein, Jeffrey R. Jasper, Ron G. Rosenfeld, Raymond L. Hintz

Research output: Contribution to journalArticle

29 Scopus citations


To determine whether chronic hypoxemia results in alterations in endocrine function that may contribute to growth failure, we measured growth hormone (GH), somatomedins (insulin-like growth factors I and II, IGF-I and IGF-2), hepatic growth hormone receptors, and circulating IGF-binding proteins IGFBP-3 and IGFBP-2 in 12 newborn lambs with surgically created pulmonic stenosis and atrial septal defect, and in 10 controls. During chronic hypoxemia (oxygen saturation of 60-74% for 2 wk), weight gain was 60% of control (hypoxemic, 135±20 vs. control, 216±26 g/d, P < 0.02). IGF-I was decreased by 43% (hypoxemic 253.6±29.3 SE vs. control 448.0±75.5 ng/ml, P = 0.01), whereas GH was unchanged (19.9±5.1 vs. 11.9±3.0 ng/ml, NS). The increase in IGF-1 was associated with a decrease in IGFBP-3 (hypoxemic, 5.09±1.25 vs. control, 11.2±1.08 arbitrary absorbency units per mm (Au · mm), P <0.01), and increase in IGFBP-2 (0.47±0.03 vs. 0.19±0.13 Au · mm, P < 0.05), but no significant downregulation of hepatic GH receptors (hypoxemic, 106.1±20.1 vs. control, 147.3±25.9 fmol/mg, NS). Thus, chronic hypoxemia in the newborn is associated with a decrease in IGF-I and IGFBP-3 in the face of normal GH. This suggests peripheral GH unresponsiveness, similar to protein-calorie malnutrition or GH receptor deficiency dwarfism, but mediated at a level distal to the hepatic GH receptor.

Original languageEnglish (US)
Pages (from-to)1128-1132
Number of pages5
JournalJournal of Clinical Investigation
Issue number4
StatePublished - Jan 1 1992



  • Failure to thrive
  • Hypoxia
  • Somatomedins

ASJC Scopus subject areas

  • Medicine(all)

Cite this