Ligation of the uterine artery and early postnatal food restriction - animal models for growth retardation.

Intrauterine growth restriction (IUGR) is one of the major causes of short stature in child- and adulthood. The cause of IUGR is unknown, however, an impaired uteroplacental function during the second half of human pregnancy might be an important factor, by affecting the programming of somatotropic axis and leading to postnatal growth failure into adulthood. Two rat models with perinatally induced growth retardation were used to examine the long-term effects of perinatal insults on growth. IUGR rats were prepared from pregnant dams, with a bilateral uterine artery ligation at day 17 of their pregnancy. Since the rat is relatively immature at birth, an early postnatal food restriction model was included as another model to broaden the time window of sensitive period of organogenesis. An individual growth curve was calculated of each animal (n = 813). From these individual growth curves the predicted growth curve for each experimental group was calculated by multilevel analysis. The proposed mathematical model allows us to estimate the growth potentials of these rat models with precision and could provide basic information to investigate the relationships among a number of other variables in future studies. Furthermore, we concluded that both pre- and early postnatal malnutrition leads to irreversible slowing down of postnatal growth.

Adult height in patients with early onset of Crohn's disease.

BACKGROUND: Growth impairment during childhood and adolescence is a common problem faced by patients with an early onset of Crohn's disease. AIMS: To establish how the final adult height is affected in patients with early onset of symptoms of Crohn's disease. METHODS: Information on height, parental height, and disease history was obtained from 135 patients with Crohn's disease who reached their adult height (men 22-40 years, women 18-40 years) using a questionnaire and by outpatient measurement of height where possible. Subsequently, adult heights were expressed as standard deviation scores, with and without correction for the expected target height. RESULTS: Patients with onset of disease before puberty were shorter compared with patients with onset in adulthood (p<0.01). This difference was not statistically significant when adult heights were corrected for parental height. Also, height standard deviation scores for those patients with onset of disease before puberty were significantly lower than those with onset of disease during puberty (p<0.05) but after correction for parental height the difference was not significant. The site of disease had no influence on adult height. Patients who had used corticosteroids during puberty were significantly shorter than patients who had not (p=0.005). This was also true when corrected for target height (p=0.007). CONCLUSIONS: Although there was a trend indicating a deficit in adult height in patients with an early onset of Crohn's disease, once adjustment was made for parental height, this difference was not significant. Use of corticosteroids in puberty resulted in lower adult height.

Final height gain by GH therapy in children with idiopathic short stature is dose dependent.

Recombinant human GH therapy to children with idiopathic short stature (ISS) increases growth velocity, but its effect on final height (FH) is still uncertain. The aim of this study was to investigate the effect of recombinant human GH on FH of patients with ISS who were treated according to two protocols in comparison to untreated historical controls. In study 1 (n = 24), all patients were treated with 14 IU (4.6 mg)/m(2) body surface x wk in the first year; thereafter the dosage was doubled if the growth response was insufficient. In study 2 (n = 34), patients were randomized into three arms: 18 IU (6 mg)/m(2) x wk; 27 IU (9 mg)/m(2) x wk; and 18 IU/m(2) x wk in the first year, followed by 27 IU/m(2) x wk thereafter. Observed or estimated FH was available for 53 patients. Thirty-four untreated controls from the same centers were available for comparison. Mean FH SD score in GH-treated children was -2.1, vs. -2.4 in controls (-2.4) (NS), but height SD score gain (1.3 vs. 0.7) and the difference between FH and predicted adult height (4.0 vs. 0.8 cm) were significantly greater. The growth response on an initial dosage of 27 IU/m(2) x wk (6.9 cm) was significantly better than on other regimens (2.8 cm). We conclude that a GH dosage of 27 IU (9 mg)/m(2) x wk to prepubertal children with ISS leads to a mean FH gain of approximately 7 cm, whereas regimens starting on lower dosages are less efficacious.