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Reference Values for Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and the Ratio of Insulin-Like Growth Factor-I to IGFBP-3 throughout Childhood and Adolescence

Göteborg Pediatric Growth Research Center (C.L., L.G., S.R., K.A.W.), Institute for the Health of Women and Children, Department of Clinical Nutrition (L.H.), The Sahlgrenska Academy at Göteborg University, and Department of Statistics (E.A.), University of Göteborg, S-416 85 Göteborg, Sweden; and University Children’s Hospital (W.F.B.), 35392 Giessen, Germany

Address all correspondence and requests for reprints to: Chatarina Löfqvist, The Sahlgrenska Academy at Göteborg University, Institute for the Health of Women and Children, Göteborg Pediatric Growth Research Center, The Queen Silvia Children’s Hospital, S-416 85 Göteborg, Sweden. E-mail: chatarina.lofqvist{at}vgregion.se.

To facilitate the diagnosis of GH deficiency and monitor GH therapy, we constructed two reference models to allow comparison of serum IGF binding protein (IGFBP)-3 concentrations and IGF-I to IGFBP-3 ratios among children throughout childhood and adolescence. This report presents equations for determining the SD score of IGFBP-3 and IGF-I to IGFBP-3 measurements for individual patients. The data set contains serum values from 468 healthy children and adolescents (232 males, 236 females; ages 1.1–18.3 yr) whose height, weight, and body mass index were within ± 3 SD of means. Puberty was classified according to breast development (B) and testicular volume into pre-, early, mid-, and late puberty. The values of IGFBP-3 and IGF-I to IGFBP-3 ratios were log transformed, and multiple linear regression analysis was used to identify models for converting serum concentrations into SD scores. The models include the variables of age, gender, and puberty and take into account the interactions among these variables. The best linear models explain 42% of the variation in serum IGFBP-3 concentrations and 50% of the variation in serum IGF-I to IGFBP-3 concentrations.

The relationship between age and log(IGFBP-3) was positive for boys in pre-, early, and midpuberty. In late puberty, values were higher than earlier in puberty, and there was a negative relationship with age. For girls the relationship between age and log(IGFBP-3) also was positive in pre- and early puberty, with larger effect for girls older than 8 yr. Values for girls in midpuberty were relatively constant, and in late puberty values were higher than earlier in puberty, and there was a negative relationship with age.

The relationship between age and log(IGF-I to IGFBP-3 ratio) was positive for boys in pre-, early, and early midpuberty (volume = 9–14 ml). In late midpuberty (volume = 15–19 ml), the relationship between age and IGF-I to IGFBP-3 ratio was negative. In late puberty, values were relatively constant and higher than earlier in puberty. For girls in prepuberty, the relationship with age was positive, with a larger effect in girls older than 8 yr. In early puberty, the girls’ values were relatively constant. In early midpuberty (B = 3), log(IGF-I to IGFBP-3 ratio) values were higher for girls than boys of the same age. In late midpuberty (B = 4), the relationship with age was negative, and in late puberty values were relatively constant and higher than earlier in puberty.

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