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A 5-Year Prospective Study of Growth Hormone (GH)-Deficient Children Treated with GH before the Age of 3 Years¹

Pediatric Endocrinology Unit, Hôpital des Enfants Malades (R.R., E.M., R.B., H.C.), and the Pediatric Endocrinology Unit, Hôpital Robert Debré (J.L., P.C.), Paris; Hôpital Pédiatrique (J.M.L.), Angers; Hôpital Purpan (P.R.), Toulouse; and Hôpital Hautepierre (S.S.), Strasbourg, France; and Alpha 5 (C.L.), Riva San Vitale, Switzerland

Address all correspondence and requests for reprints to: R. Rappaport, M.D., Unité d’Endocrinologie Pédiatrique, Hôpital des Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.

The aim of the study was to assess the efficacy of GH therapy in GH-deficient children treated before the age of 3 yr. A noncomparative multicenter prospective study included 49 children (22 girls and 27 boys) with isolated GH deficiency (n = 19) or multiple pituitary hormone deficiency (n = 30) treated with daily sc injections (0.6 U/kg·week) for 3–5 yr. They were divided into two groups according to their height SD score for chronological age (CA) at the initiation of therapy: group A consisted of 8 patients presenting an initial height within the normal range (<2 SD below the mean) followed for 2–5 yr, and group B consisted of 25 children followed for 5 yr among 41 patients with initial growth retardation.

In group A, the mean height SD score increased from -1.1 ± 0.6 to 0.35 ± 1.0 SD (P < 0.001) in the first year and remained in the normal range throughout the following 4 yr. In group B after 4 yr of treatment, the mean height SD score for age had increased from -3.6 ± 1.0 SD (time zero) to -0.9 ± 1.2 SD. During the fourth year of therapy, the mean height gain of 0.2 ± 0.2 SD was significant (P < 0.001). After 5 yr of treatment, a plateau was reached with a corresponding height SD score (CA) of -0.8 ± 1.2 SD (95% confidence interval between -1.3 and -0.2 SD). This value remained significantly below normal for age (P < 0.001), indicating that catch-up growth was incomplete. Only four patients (16%) remained below -2SD for CA. The 5-yr height gain was negatively correlated with the height SD score at the start of treatment (r = -0.6; P < 0.005) and the first year height gain was the most predictive parameter. There was no significant influence of intrauterine growth retardation, body mass index and age at the start of treatment, or parental target height. Bone maturation was significantly retarded over CA by a mean value of 1.1 ± 0.9 yr (P < 0.0001), with a mean bone age/CA ratio of 0.8 ± 0.2 after a mean treatment duration of 5.1 ± 1.1 yr.

In conclusion, the rapid and almost complete return to normal height obtained in this study supports the need for GH treatment in early diagnosed GH-deficient children. The present dosage may be considered the minimum to obtain satisfactory catch-up growth ensuring a favorable outcome for these children. In addition, it allowed growth at a rate normal for age in patients diagnosed before growth retardation.

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