Intrauterine growth retardation: Evidence for the activation of the insulin-like growth factor (IGF)-related growth-promoting machinery and the presence of a cation-independent IGF binding protein-3 proteolytic activity by two months of life

Stefano Cianfarani, Daniela Germani, Paola Rossi, Laura Rossi, Angela Germani, Cristina Ossicini, Antonio Zuppa, Giovanni Argirò, Jeffrey M P Holly, Francesco Branca

Research output: Contribution to journalArticlepeer-review

Abstract

Thirty-seven children with intrauterine growth retardation (IUGR) were enrolled in a 3-mo longitudinal study. Weight, length, and knee-heel length (by knemometry) were measured at birth and at 7, 14, 30, 60, and 90 d. GH, IGF-I, IGF binding protein (BP)-3, IGFBP-1, and C-peptide were measured at birth and at 2 mo. IGFBP-3 Western immunoblotting and proteolytic activity assay were also performed. Twenty-five newborns with birth weight appropriate for gestational age were chosen as controls. At birth IUGR newborns showed levels of GH and IGFBP-1 significantly higher, and IGF-I, IGFBP-3, and C- peptide significantly lower than control subjects. At 2 mo GH and IGFBP-1 levels decreased, whereas IGF-I, IGFBP-3, and C-peptide rose, attaining the concentrations found in control subjects at birth. Baseline peptide levels as well as their 2-mo variations did not correlate with the gain in weight, supine length, and knee-heel length recorded at 3 mo. Fourteen of nineteen IUGR cord blood samples showed the presence of the intact ~42-39-kD IGFBP-3 doublet and the major ~29-kD fragment. At 2 mo the IGFBP-3 band pattern was characterized by the predominance of a ~18-kD fragment in 6 of 19 tested IUGR infants. The incubation of 2-mo IUGR samples with normal adult serum induced the appearance of the ~18-kD band, which was not modified by the addition of EDTA. These results suggest that: 1) the IGF-related growth- promoting mechanism is impaired in IUGR children at birth but is fully restored at 2 mo; 2) the cord blood levels of GH, IGF-I, IGFBP-3, IGFBP-1, and C-peptide are not predictive of the weight and length gain during the first 3 mo of life; 3) IUGR children have at least two different IGFBP-3 proteases, one cation-dependent protease that is present at birth and able to yield the major ~29-kD IGFBP-3 fragment and a second one, with a different activation timing, which exhibits cation independence and induces the formation of a ~18-kD IGFBP-3 form.

Original languageEnglish
Pages (from-to)374-380
Number of pages7
JournalPediatric Research
Volume44
Issue number3
Publication statusPublished - Sep 1998

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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