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Early, Discontinuous, High Dose Growth Hormone Treatment to Normalize Height and Weight of Short Children Born Small for Gestational Age: Results Over 6 Years

The Belgian Study Group for Pediatric Endocrinology and the Departments of Pediatrics, Universities of Leuven (F.d.Z., K.V.), Antwerp (M.V.L.D.C.), Bruxelles (C.H.), Louvain (M.M., P.M.), Brussels (J.D.S.), and Ghent (M.C.), Belgium; and the Department of Pediatrics, Oregon Health Sciences University (R.G.R.), Portland, Oregon 97201

Address all correspondence and requests for reprints to: Francis de Zegher, M.D., Ph.D., Department of Pediatrics, University Hospital Gasthuisberg, 3000 Leuven, Belgium.

Most children born small for gestational age (SGA) normalize their size through spontaneous catch-up growth within the first 2 yr after birth. Some SGA children fail to do so and maintain an abnormally short stature throughout childhood. We have previously reported that high dose GH treatment (66 or 100 µg/kg·day sc over 2 yr; age at start, 2–8 yr; n = 38) induces pronounced catch-up growth in short children born SGA, thereby normalizing their height and weight in childhood. Here, we report on the further prepubertal growth course of these children over the first 4 yr after withdrawal of early, high dose GH treatment.

Of the 38 treated children, none developed precocious puberty, and 22 remained prepubertal. Mean age of the latter at start of GH was 4.4 yr, height was -3.7 SD score, and height after adjustment for midparental height was -2.9 SD score. Height increased by an average of 2.5 SD during the 2 yr of GH treatment and decreased by 0.4 and 0.3 SD, respectively, during the first and second year after GH withdrawal. Subsequently, when stature was not extremely short at the start (mean adjusted height SD score, -2.7; n = 13), no further GH treatment was given, and the adjusted height was stabilized around -1.0 SD score; when stature was very short at the start (mean adjusted height, -3.3 SD score; n = 9), a second course of GH treatment (66 µg/kg·day sc) was initiated either 2 yr (n = 5) or 3 yr (n = 4) after initial GH withdrawal. This second course was associated with renewed catch-up growth and also resulted in a mean adjusted height of -1.0 SD score. In each subgroup, the pattern of the weight course paralleled that of the height course; GH treatment was well tolerated.

In conclusion, early, discontinuous, high dose GH treatment appears to be a safe and efficient option to normalize prepubertal height and weight in the majority of short SGA children. It remains to be examined whether the normalized stature will be maintained during pubertal development, either with or without further GH treatment.

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