Size at birth and cord blood levels of insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and the soluble IGF-II/mannose-6-phosphate receptor in term human infants. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood

J Clin Endocrinol Metab. 2000 Nov;85(11):4266-9. doi: 10.1210/jcem.85.11.6998.


Experimental rodent studies demonstrate that insulin-like growth factor II (IGF-II) promotes fetal growth, whereas the nonsignaling IGF-II receptor (IGF2R) is inhibitory; in humans their influence is as yet unclear. A soluble, circulating form of IGF2R inhibits IGF-II mediated DNA synthesis and may therefore restrain fetal growth. We measured cord blood levels of IGF-II, soluble IGF2R, insulin, IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and examined their relationships to weight, length, head circumference, ponderal index, and placental weight at birth in 199 normal term singletons. IGF-II levels correlated with levels of IGF-I (r = 0.29; P < 0.0005), IGFBP-3 (r = 0.45; P < 0.0005), and soluble IGF2R (r = 0.20; P < 0.005). Insulin and IGF-I were positively related to all parameters of size at birth. IGF-II was weakly related to ponderal index (r = 0.18; P < 0.05) and placental weight (r = 0.18; P < 0.05), and the molar ratio of IGF-II to IGF2R was also related to birth weight (r = 0.15; P < 0.05). Correlations between the IGFs and size at birth were stronger in nonprimiparous pregnancies; in these, IGF-I (r = 0.52; P < 0.0005), IGFBP-3 (r = 0.41; P < 0.0005), and the IGF-II to IGF2R ratio (r = 0.40; P < 0.0005) were most closely related to placental weight, together accounting for 39% of its variance. We demonstrate for the first time relationships between circulating IGF-II and soluble IGF2R levels and size at birth, supporting their putative opposing roles in human fetal growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Constitution*
  • Cohort Studies
  • Female
  • Fetal Blood / chemistry*
  • Human Growth Hormone / blood
  • Humans
  • Infant, Newborn*
  • Insulin / blood*
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor II / analysis*
  • Male
  • Placenta
  • Pregnancy
  • Receptor, IGF Type 2 / blood*
  • Reference Values
  • Regression Analysis


  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Receptor, IGF Type 2
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II