Size in small-for-gestational-age neonates correlates with IGFBP proteolysis and IGF-I bioavailability

Context Alterations in prenatal growth affect postnatal outcomes, but the factors involved in prenatal growth are not clearly defined. Cord blood levels of insulin-like growth factor (IGF)-I are associated with weight and length at birth; however, how pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF-binding protein (IGFBP) cleavage and IGF bioavailability in relation to birth size and nutritional status in full-term neonates is unknown. Objective We aimed to determine the relationship between serum levels of PAPP-As and STCs with other components of the IGF axis and ponderal index (PI) in full-term small (SGA), appropriate (AGA), or large (LGA) for gestational age neonates (according to gestational age or PI). Methods Twenty-six SGA, 131 AGA and 22 LGA neonates were studied and circulating levels of IGF axis parameters were evaluated according to weight, length, weight-to-length ratio, and PI. Results SGA newborns had lower total and free IGF-I, total IGFBP-3, acid-labile subunit, and PAPP-A2 levels, and higher total IGFBP-1 and -2, intact IGFBP-4, and STC-1 levels than AGA newborns. Neonates in the first tertile of PI had lower total and free IGF-I and IGFBP-5, and higher IGFBP-1 and -2 levels than those in the third tertile. PAPP-A2 levels correlated positively with weight and length, and inversely with IGFBP-4 and STC-1 levels. IGF-I and PAPP-A2 levels are associated with length. Conclusion Variations in IGF-I parameters, such as STCs and PAPPAs, according to length/weight or PI suggest that they play an important role in intrauterine growth and/or nutritional status.