Growth hormone therapy for short children born small for gestational age.
ABSTRACT Children born small for gestational age may demonstrate continued growth retardation, resulting in persistent short stature. In the majority of the cases, this is linked with abnormal growth hormone secretion and also abnormal insulin-like growth factor levels. This review discusses the treatment of such children with recombinant human growth hormone. It illustrates the importance of starting therapy early, the dose-dependent response, and the advantages of continuous therapy and describes safety considerations.
- SourceAvailable from: Hans M Koot[show abstract] [hide abstract]
ABSTRACT: Short stature is not the only problem faced by small for gestational age (SGA) children. Being born SGA has also been associated with lowered intelligence, poor academic performance, low social competence, and behavioral problems. Although GH treatment in short children born SGA can result in a normalization of height during childhood, the effect of GH treatment on intelligence and psychosocial functioning remains to be investigated. We show the longitudinal results of a randomized, double-blind, GH-dose response study initiated in 1991 to follow growth, intelligence quotient (IQ), and psychosocial functioning in SGA children during long-term GH treatment. Patients were assigned to one of two treatment groups (1 or 2 mg GH/m(2) body surface.d, or approximately 0.035 or 0.07 mg/kg.d). Intelligence and psychosocial functioning were evaluated at start of GH treatment (n = 74), after 2 yr of GH treatment (n = 76), and in 2001 (n = 53). IQ was assessed by a short-form Wechsler Intelligence Scale for Children-Revised or Wechsler Adult Intelligence Scale (Block-design and Vocabulary subtests). Behavioral problems were measured by the Achenbach Child Behavior Checklist or Young Adult Behavior Checklist, and self-perception was measured by the Harter Self-Perception Profile. Mean (sem) birth length sd score was -3.6 (0.2), mean age and height at start was 7.4 (0.2) yr and -3.0 (0.1) sd score, respectively, mean duration of GH treatment was 8.0 (0.2) yr, and mean age in 2001 was 16.5 (0.3) yr. After 2 yr of GH treatment, 96% of both GH groups showed a height gain sd score of 1 sd from the start of treatment or more, resulting in a normal height (i.e. height >/= -2.0 sd for age and sex) in 70% of the children. In 2001, 48 (91%) of the 53 children participating in this study had reached a normal height. Block-design s-score and the estimated total IQ significantly increased (P < 0.001 and P < 0.001, respectively) from scores significantly lower than Dutch peers at start (P < 0.001 and P < 0.001, respectively) to comparable scores in 2001. The increase over time for the Vocabulary s-score was not significant. Internalizing Behavior sd scores remained comparable to Dutch peers, whereas Externalizing Behavior sd scores and Total Problem Behavior sd scores improved significantly during GH therapy (P < 0.01 and P < 0.05, respectively) to scores comparable to Dutch peers. Self-perception sd scores improved from start of GH treatment until 2001 (P < 0.001) to scores significantly higher than Dutch peers (P < 0.05). No significant differences between the two GH dosage groups were found. Improvement in Externalizing and Total Problem Behavior sd scores over time was significantly related to change in height sd score (P < 0.05 and P < 0.01, respectively), whereas scores over time for Vocabulary, Block-design, Internalizing, or total Harter Self-Perception score were not related to change in height sd scores. In conclusion, parallel to a GH-induced catch-up growth in adolescents born SGA, IQ, behavior, and self-perception showed a significant improvement over time from scores below average to scores comparable to Dutch peers. In addition, children whose height over time became closer to that of their peers showed less problem behavior.Journal of Clinical Endocrinology & Metabolism 11/2004; 89(11):5295-302. · 6.43 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Human GH (hGH) treatment leads to catch-up growth in children with short stature born small for gestational age (SGA). However, long-term efficacy and safety results in this patient group remain scarce. The present study assessed the efficacy and safety of late childhood treatment with biosynthetic hGH (Humatrope) in a group of short children born SGA (height <-2 standard deviation scores (SDS)). Patients in this open-label, Phase III, multicenter study received a daily hGH dose of 0.067 mg/kg for 2 years, and then received no treatment for the following 2 years. After the fourth year on study, patients whose height had decreased more than 0.5 SDS but who still showed growth potential based on bone age were allowed to resume treatment until they reached adult height. Height gain SDS was assessed for 11 girls and 24 boys (mean age+/-s.d. 9.6+/-0.9 years) at the end of the 2 years of hGH treatment, during the subsequent 2-year off-treatment period, and upon reaching adult height. At the end of the initial 2-year treatment period, 83% of patients had reached a height within the normal range, with a mean increase in height SDS vs baseline of 1.3+/-0.3 (P <0.001). Adult heights (n = 20) were within the normal range for 50% of patients, and mean height gain from baseline was statistically significant (0.7+/-0.8 SDS, P <0.001). Fasting glucose and glycosylated hemoglobin levels were not significantly modified during treatment. High-dose hGH treatment for a minimum of 2 years in short children born SGA was well tolerated and resulted in a significant increase in adolescent and adult height.European Journal of Endocrinology 07/2005; 152(6):835-43. · 3.14 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: To determine whether hyperinsulinemia and reduced insulin sensitivity in individuals born small for gestational age (SGA) could be related to persisting abnormalities of the GH/IGF-I axis, we assessed overnight GH secretory profiles and measured fasting glucose, insulin, intact and 32,33 split proinsulin, and IGF-I levels in 16 short SGA children (age range 2.3-8.0 y) and in controls. Insulin sensitivity was calculated using the homeostasis model. Compared with short normal-birthweight controls (n = 7, age range 2.3-5.0 y), short SGA children had higher fasting insulin levels (means: 26.8 vs 20.6 pmol/L, p = 0.02), lower insulin sensitivity [means: 204 vs 284 %homeostasis model assessment (HOMA), p = 0.01], and higher beta cell function (112 vs 89 %HOMA, p = 0.04). SGA children also had lower levels of IGFBP-1 (87.0 vs 133.8, p = 0.04), but similar IGF-I levels (IGF-I SDS: -1.1 vs -1.7, p = 0.4). Compared with normal-height controls (n = 15, age range 5.6-12.1 y), SGA children had higher overnight GH secretion (GH maximum: 55.9 vs 39.6 mU/L, p = 0.01; mean: 13.1 vs 8.9, p = 0.004; minimum: 1.2 vs 0.6, p = 0.02). Interestingly, among SGA children, fasting insulin levels and insulin sensitivity were significantly related to overnight GH secretion (insulin sensitivity vs maximum GH: r = -0.68, p = 0.01; vs GH pulse amplitude r = -0.71, p = 0.007). The only hormone level significantly related to current height velocity was C-peptide (r = 0.75, p = 0.008). In conclusion, elevated fasting insulin levels and reduced insulin sensitivity in short SGA children was related to elevated levels of overnight GH secretion. We hypothesize that resistance to the somatotropic actions of GH and IGF-I in short SGA children may contribute directly to reduced insulin sensitivity.Pediatric Research 02/2002; 51(1):76-80. · 2.67 Impact Factor