Size in small-for-gestational-age neonates correlates with insulin-like growth factor–binding protein proteolysis and insulin-like growth factor-I bioavailability

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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 (pregnancy-associated plasma protein [PAPP]-A and PAPP-A2) and stanniocalcins (STC-1 and 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-A and STCs with other components of the IGF axis and ponderal index (PI) in full-term small-for-gestational-age (SGA), adequate-for-gestational-age (AGA), or large-for-gestational-age (LGA) 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: Small-for-gestational-age newborns had lower total and free IGF-I, total IGFBP-3, acid-labile subunit, and PAPP-A2 levels and higher total IGFBP-1 and IGFBP-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. Pregnancy-associated plasma protein-A2 levels correlated positively with weight and length and inversely with IGFBP-4 and STC-1 levels. Insulin-like growth factor-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.

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