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Growth Hormone Treatment in Children with Short Stature Born Small for Gestational Age: 5-Year Results of a Randomized, Double-Blind, Dose-Response Trial¹

Department of Pediatrics, Division of Endocrinology, Sophia Children’s Hospital/Erasmus University (Th.S., W.d.W., A.H.-K.), 3015 GJ Rotterdam; Institute of Epidemiology and Biostatistics, Erasmus University (P.M.), 3015 GJ Rotterdam; Academic Hospital of Free University (M.H.), 1081 HV Amsterdam; Wilhelmina Children’s Hospital (M.J.), 3584 EA Utrecht; and Juliana Children’s Hospital (M.R.), 2566 ER The Hague, The Netherlands

Address all correspondence and requests for reprints to: Th. C. J. Sas, M.D., Sophia Children’s Hospital, Department of Pediatrics, Division of Endocrinology, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.

The growth-promoting effect of continuous GH treatment was evaluated over 5 yr in 79 children with short stature (height SD score, less than -1.88) born small for gestational age (SGA; birth length SD score, less than -1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage groups (3 vs. 6 IU/m² body surface·day). GH deficiency was not an exclusion criterium. After 5 yr of GH treatment almost every child had reached a height well within the normal range for healthy Dutch children and in the range of their target height SD score. Only in children who remained prepubertal during the study period was the 5-yr increase in height SD score (HSDS) for chronological age significantly higher in the study group receiving 6 compared to 3 IU GH/m²·day. Remarkably, the 5-yr increment in HSDS for chronological age was not related to spontaneous GH secretion, maximum GH levels after provocation, or baseline insulin-like growth factor I levels. GH treatment was associated with an acceleration of bone maturation regardless of the GH dose given. The HSDS for bone age and predicted adult height increased significantly. GH treatment was well tolerated.

In conclusion, our 5-yr data show that long term continuous GH treatment at a dose of 3 or 6 IU/m²·day in short children born SGA results in a normalization of height during childhood followed by growth along the target height percentile.

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