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Smallness for Gestational Age Is Associated with Persistent Change in Insulin-Like Growth Factor I (IGF-I) and the Ratio of IGF-I/IGF-Binding Protein-3 in Adulthood

Institut National de la Santé et de la Recherche Médicale, Unité 690 (R.V., D.J., S.D., P.C., C.L.-M.), and Department of Biochemistry (D.C.), Hôpital Robert Debré, 75019 Paris, France

Address all correspondence and requests for reprints to: Dr. Rasa Verkauskiene, Institut National de la Santé et de la Recherche Médicale, Unité de Recherche 690, Hôpital Robert Debré, 48 Boulevard Serurier, 75019 Paris, France. E-mail: verkauskiene{at}rdebre.inserm.fr.

Context: Implication of the IGF-IGF-binding protein (IGFBP) axis in the development of metabolic and cardiovascular diseases has been well documented. It has also been shown that an adverse intrauterine environment alters the IGF-IGFBP axis during childhood.

Objective: The objective of this study was to investigate whether these alterations persist into adulthood.

Design and Methods: Fasting serum IGF-I, IGFBP-3, and insulin concentrations were measured, and their determinants were analyzed in a cohort of young adult subjects (22 yr of age) born either small (SGA; n = 461) or appropriate (AGA; n = 568) for gestational age.

Results: In adulthood, subjects born SGA had significantly lower mean serum IGF-I (320 ± 137 vs. 348 ± 143 µg/liter; P = 0.0015), IGFBP-3 (4700 ± 700 vs. 4800 ± 800 µg/liter; P = 0.04), and IGF-I/IGFBP-3 ratio (0.067 ± 0.026 vs. 0.072 ± 0.025; P = 0.01) than those born AGA. The fasting IGF-I concentration and the IGF-I/IGFBP-3 ratio were significantly inversely associated with age, body mass index, smoking, and oral contraception and were positively related to birth weight and fasting insulin levels. The IGFBP-3 concentration was significantly negatively correlated to age and smoking and was positively related to insulin concentration and oral contraception. After adjustment for age, height, body mass index, gender, smoking, and oral contraception, the mean IGF-I concentration and the mean IGF-I/IGFBP-3 ratio remained significantly lower in the SGA compared with the AGA group (P = 0.003 and P = 0.01, respectively).

Conclusions: Serum IGF-I concentrations and the IGF-I/IGFBP-3 ratio are lower in adult subjects born SGA. Although the origin of this persisting alteration of the IGF-IGFBP axis in adulthood needs to be elucidated, its potential contribution to the long-term metabolic and cardiovascular complications associated with fetal growth restriction is important to consider in the future.

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