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Department of Pediatrics, Division of Endocrinology, Sophia Children’s Hospital/Erasmus Medical Center (Y.v.P., A.H.-K.), 3015 GJ Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics, Erasmus Medical Center (P.M.), 3015 GJ Rotterdam, The Netherlands; Academic Hospital of Free University (M.H.), 1081 HV Amsterdam, The Netherlands; Wilhelmina Children’s Hospital (M.J.), 3584 EA Utrecht, The Netherlands; and Juliana Children’s Hospital (M.R.), 2566 MJ The Hague, The Netherlands
Address all correspondence and requests for reprints to: A. C. S. Hokken-Koelega, M.D., Department of Pediatrics, Division of Endocrinology, Sophia Children’s Hospital, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.
The GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly assigned to treatment with either 3 IU (group A) or 6 IU (group B) GH/m2·d (
0.033 or 0.067 mg/kg·d, respectively). The mean (±SD) birth length was -3.6 (1.4), the age at the start of the study was 8.1 (1.9) yr, and the height SD score (SDS) at the start of the study -3.0 (0.7). Seventeen of the 54 children were partially GH deficient (stimulated GH peak, 10–20 mU/liter). Fifteen non-GH-treated, non-GH-deficient, short children born SGA, with similar inclusion criteria, served as controls [mean (±SD) birth length, -3.3 (1.2); age at start, 7.8 (1.7) yr; height SDS at start, -2.6 (0.5)]. GH treatment resulted in an AH above -2 SDS in 85% of the children after a mean (±SD) GH treatment period of 7.8 (1.7) yr. The mean (SD) AH SDS was -1.1 (0.7) for group A and -0.9 (0.8) for group B, resulting from a mean (±SD) gain in height SDS of 1.8 (0.7) for group A and 2.1 (0.8) for group B. No significant differences between groups A and B were found for AH SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.2, 0.6; P > 0.2) and gain in height SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.1, 0.7; P > 0.1). When corrected for target height, the mean corrected AH SDS was -0.2 (0.8) for group A and -0.4 (0.9) for group B. The mean (±SD) AH SDS of the control group [-2.3 (0.7)] was significantly lower than that of the GH-treated group (P < 0.001). Multiple regression analysis indicated the following predictive variables for AH SDS: target height SDS, height SDS, and chronological age minus bone age (years) at the start of the study. GH dose had no significant effect. In conclusion, long-term continuous GH treatment in short children born SGA without signs of persistent catch-up growth leads to a normalization of AH, even with a GH dose of 3 IU/m2·d (0.033 mg/kg·d).
This work was supported by Novo Nordisk A/S (Bagsvaerd, Denmark).
Abbreviations: AH, Adult height; ATT, arginine tolerance test; BA, bone age; BMI, body mass index; CA, chronological age; CI, confidence interval; GHD, GH deficiency; HV, height velocity; PI, prediction interval; SDS, SD score; SGA, small for gestational age; TH, target height.
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