Fluticasone in the therapy of asthmatic children: short-term effects on growth

AIM: Inhaled corticosteroids (ICS), for years used in the therapy of low-moderate bronchial asthma, reduce the rate of asthmatic attack with improved pulmonary functioning and quality of life. Clinical trials have been addressed mainly to study the efficacy rather than the safety of drugs, so that the side effects of these drugs have not yet been accurately defined. Clinical experience shows that growth delay appears in the first months of therapy with ICS. The aim of the study was to evaluate the influence of the therapy with spacer-administered inhaled corticosteroid on short-term auxological development in prepubertal children. METHODS: In a group of children with low asthma, height and weight have been evaluated before and after six months of inhaled therapy with dipropionate fluticasone at a dose of 100 microg per day. RESULTS: Twenty-five patients (19 males and 6 females; age 5.5+/-1.6 years; range: 2.6-7.8 years) showed a regular growth during the six months of therapy (mean height 0.8 standard deviation score [SDS] before therapy and 0.8 SDS after therapy), while 21 (17 males and 4 females; age 10.0+/-1.5 years; range 8.0-12.7 years) showed an increment of growth rate (mean height from 0.5 SDS to 0.7 SDS, respectively). CONCLUSION: Spacer-administered low dose fluticasone does not negatively influence short-term growth rate, regardless of the age of the patients.     

One-year treatment with recombinant human growth hormone of children with meningomyelocele and growth hormone deficiency: a comparison of supine length and arm span.

Growth retardation and precocious puberty are frequently found in children with meningomyelocele (MMC). Lower limb contractions, spasticity and kyphoscoliosis may lead to disproportionate short stature. Most of these patients have structural brain defects or hydrocephalus which can cause growth hormone deficiency. In this study, 19 children aged between 3.5 and 12.8 years with MMC and growth hormone (GH) deficiency were treated with recombinant human GH for a period of 12 months. Supine length, arm span and growth velocity were compared before, and after 6 and 12 months of treatment with rhGH (daily dose 2.0 IU/m2 BSA s.c.). Mean supine length standard deviation score (SDS) increased by +0.8 SDS after 6 months and +1.2 SDS after 12 months of therapy. Mean arm span standard deviation score increased by +0.9 SDS and +1.3 SDS. Growth velocity increased in supine length from 3.3 cm/yr (-2.1 SDS) to 8.4 cm/yr (+2.4 SDS) and in arm span from 4.8 cm/yr (-1.3 SDS) to 8.6 cm/yr (+3.1 SDS) in the first 6 months and was 8.1 cm/yr (+2.4 SDS) and 8.3 cm/yr (+2.6 SDS) after 12 months of therapy. Linear correlation between SDS growth velocity supine length and SDS growth velocity arm span during one year of treatment was excellent (r = 0.65, p < 0.0025). We surmise that body proportions do not deteriorate when growth velocity is stimulated in MMC patients. Both supine length and arm span measurements are necessary to document growth in children with spinal dysraphism.     

Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect

OBJECTIVES: To investigate in an open-label randomized study, the effect of two doses of growth hormone (GH) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature (mean baseline height standard deviation score [SDS] -3.2). STUDY DESIGN: Patients were treated with GH at 0.24 mg/kg/week, 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter (0.24-->0.37), or 0.37 mg/kg/week. Final height was evaluated in 50 patients at study completion (mean treatment duration, 6.5 years). RESULTS: Patients who received 0.37 mg/kg/week (n = 72) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week (n = 70) (treatment difference = 0.8 cm/year; P = .003) or 0.24-->0.37 mg/kg/week (n = 67) (treatment difference = 0.9 cm/year; P = .001). For the 50 patients for whom final height measurements were available, mean height SDS increased by 1.55, 1.52, and 1.85 SDS, respectively, for the three dose groups. For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, the mean treatment difference (adjusted for differences in baseline predicted height SDS) was 0.57 SDS (3.6 cm; P = .025). Mean overall height gains (final height minus baseline predicted height) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, respectively, without dose effects on safety parameters. Final height measurements were within the normal adult height range for 94% of patients randomized to 0.37 mg/kg/week who continued to final height. CONCLUSION: GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature.     

Long-term treatment with growth hormone in Noonan's syndrome

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of -2.1 (range -4.1 to - 0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from -3.3(range -4.2 to -2.2)to -2.4(range -3.3 to - 1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was -2.1) (range -3.1 to - 1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from -1.8 (range - 2.8 to - 09) to -1.2 (range - 1.6 to -0.6).     

Long-term treatment with growth hormone in Noonan's syndrome

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of -2.1 (range -4.1 to - 0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from -3.3(range -4.2 to -2.2)to -2.4(range -3.3 to - 1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was -2.1) (range -3.1 to - 1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from -1.8 (range - 2.8 to - 09) to -1.2 (range - 1.6 to -0.6).     

Final height in psychosocial short stature: is there complete catch‐up?

AIM: To determine whether children with psychosocial short stature attain their genetic height potential. METHODS: We report on 18 children (10 girls, 8 boys) diagnosed by a multidisciplinary team as having psychosocial short stature. All the children had had some kind of change in their environment (9 were separated from their families), and increased their mean height velocity standard deviation score (SDS) from -0.7 (1.3) to +3.6 (4.8) (p < 0.005) as well as their height SDS from -3.0 (0.3) to -2.6 (0.9) in the first year after the change. All the patients were postpubertal and had reached their near final height (mean age, 20.0 y; range, 16.0-23.3). RESULTS: Only 3 out of 18 had a greater final height than the mid-parental target height, 14 out of 18 had a near final height within the mid-parental target range (95% tolerance limits of the mid-parental height (+/- 2 SD = +/- 10 cm). Nevertheless, mean final height expressed in height SDS for the whole group was significantly shorter with -2.4 SDS compared with the mean of the mid-parental target height of -1.5 SDS (p < 0.001). Surprisingly, initial catch-up growth did not correlate with final height attainment. CONCLUSION: The majority of patients will attain a stature within the range of mid-parental target height, although towards the lower limit of this range.     

Long-lasting extracorporeal albumin dialysis in a child with end-stage renal disease and severe cholestasis

Abstract:  We report a case of long-lasting MARS therapy as a bridge to liver–kidney transplantation. A 26-month-old girl with congenital tubulointerstitial nephritis and severe liver fibrosis was placed on MARS for an acute-on-chronic liver failure due to sepsis. She underwent two sessions with good tolerance and recovered her previous neurological status. On the basis of pruritus, sleep, and vomiting improvement, repeated MARS sessions were performed to bridge her to combined liver–kidney transplantation. During eight months, 40 sessions were performed with the MARSmini® kit and the MARS monitor^® (Gambro, Lyon, France). The treatment significantly decreased mean pruritus score from 2.2 ± 0.9 to 0.8 ± 0.6 night-time awakening and vomiting episodes. Body weight, height, and HC were −3.2, −3.5 and −2.2 SDS before and −1.7, −4.2, −2.0 SDS after eight months on MARS therapy, respectively. The arm circumference/HC ratio increased from 0.28 to 0.31. Mean total bilirubin serum levels were 303 ± 72 μmol/L before and 214 ± 42 μmol/L after MARS cycles. Long-lasting MARS dialysis is feasible in children, decreases adverse effects of severe chronic cholestasis, and may help to preserve nutritional status prior to combined liver–kidney transplantation.     

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF-I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

ABSTRACT. Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5–12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.     

Noonan's syndrome: abnormalities of the growth hormone/IGF-I axis and the response to treatment with human biosynthetic growth hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.     

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.     

Growth hormone treatment of children with Prader-Willi syndrome affects linear growth and body composition favourably

We have compared the growth and the body composition in children with Prader-Willi syndrome (PWS) with and without growth hormone treatment (recombinant GH 0.1 IU/kg/day) after a 1-y period. Twenty-nine prepubertal children with PWS, with mean body mass index (BMI) SDS of 2.2, and 10 (control) healthy obese children with mean BMI SDS of 5.6, underwent 24-h frequent blood sampling. Both PWS and control obese children had low and similar GH levels (0.7 /ng/l ± 0.4 SD). Serum IGF-I levels, however, were significantly lower in children with PWS (-1.5 SDS ± 0.8 SD vs -0.2 SDS ±0.8 SD). The 29 PWS children were randomized into 2 groups of 15 and 14 subjects for GH treatment and no treatment, respectively. Height velocity increased from -1.9 SDS to + 6.0 SDS in the treated group ( p < 0:001) and decreased from -0.1 SDS to -1.4 SDS in the control PWS group during the study year. BMI decreased significantly for the treated group (+3.0 SDS to + 2.0 SDS). Relative fat mass decreased significantly, while fat-free mass increased ( p < 0:001) for the treated group. No significant changes were noticed in body composition in the control PWS group. In conclusion, the low spontaneous 24-h GH secretion, regardless of body weight, and the exceptional response to growth hormone treatment together with the finding of low IGF-I levels suggest that growth hormone deficiency is a common feature of PWS, as a result of hypothalamic dysfunction. Treatment with growth hormone is beneficial for the majority of PWS children.     

Is insulin-like growth factor-1 monitoring useful in assessing the response to growth hormone of growth hormone-deficient children?

OBJECTIVE: To assess the relationship between insulin-like growth factor-1 (IGF-1), the growth hormone (GH) dose utilized to treat GH-deficient children and the changes noticed in height-standard deviation score (H-SDS) and height velocity (HV). STUDY DESIGN: We studied 24 prepubertal GH-deficient patients with a mean age of 10.5 +/- 1.8 years and a mean bone age (BA) of 8.4 +/- 2.1 years. H-SDS for chronologic age (CA) and BA before therapy were -2.6 +/- 0.8 and -1.2 +/- 0.8, whereas height velocity (HV)-SDS was -1.1 +/- 1.5. Serum IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured before, after 6 and 12 months of GH, and correlated with the GH dose used. Based on the increment of IGF-1 used during treatment, patients were divided into 2 groups: G1 (>1 SDS) and G2 (<1 SDS). HV-SDS and interval height increases were analyzed. RESULTS: HV-SDS, as well as H-SDS for CA and BA during the first year of treatment, were significantly greater than before therapy. IGF-1 SDS increased significantly during the first 6 months of therapy (P <.0003), but increased no further at 12 months despite the use of a higher GH dose (0.1 vs 0.14 IU/kg/day), whereas IGFBP-3 SDS increased at both 6 and 12 months. There was no correlation between the GH dose used and IGF-1 and IGFBP-3 levels. When patients were divided according to their IGF-1 increment during therapy, a significant increase in H-SDS for BA and in HV-SDS was noted only in group 2. CONCLUSIONS: The increment in IGF-1 SDS during therapy did not correlate with the interval height increase. IGF-1 measurement may be helpful in monitoring compliance and safety, but seems to be less useful in adjusting the GH dose needed to treat prepubertal GH-deficient children.     

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

The effects of recombinant human growth hormone on linear growth in children with Crohn's disease and short stature

BACKGROUND/AIMS: The efficacy of recombinant human growth hormone (rhGH) in treating the growth failure associated with Crohn's disease (CD) is unclear. METHODS: Retrospective data analysis at 12 months before (T-12), 6 months before (T-6), at baseline (T+0), 6 months after (T+6) and 12 months after (T+12) rhGH treatment in seven patients with CD (five males). RESULTS: Median chronological age (CA) and median difference between CA and bone age was 15.9 yr (range, 13.0 to 17.9) and 1.7 yr (-0.7 to 3.3), respectively. Median dose of rhGH at T+0 was 0.23 mg/wk (0.15 to 0.31). Pubertal status remained unchanged in 6/7 patients. Median albumin and C-reactive protein (CRP) were similar at T+0 and T+6. Median height SDS at T+0, T+6 and T+12 was -2.2 (-4.0 to -1.5), -1.9 (-4.1 to -0.8), -1.9 (-4.1 to -0.7), respectively (NS). Median height velocity (HV) SDS at T+0 and T+6 was -2.5 (-4.8 to 1.4) and -0.9 (-5.3 to 3.4), respectively (NS). There was a positive correlation between percentage change in HV SDS at T+6 and dose of rhGH at T+0 (r = 0.8, p = 0.03). CONCLUSION: Introduction of rhGH therapy was associated with a cessation in the deterioration in linear growth. However, an improvement in height SDS was not observed over the period of the study. Future studies should explore the efficacy of a higher dose of rhGH in CD.     

The effect of cyproterone acetate on the growth of children with central precocious puberty

We have examined the growth and skeletal maturation of 19 children (6 male, 13 female) with central precocious puberty. The aetiology in nine patients (5 male, 4 female) was secondary to a hypothalamic hamartoma. Six children (2 male, 4 female) received no treatment whereas 13 children (4 male, 9 female) were treated with cyproterone acetate in a mean dose of 68 mg/m² per day (range, 34–260) for a mean duration of 4.5 years (range, 0.8–7.9). There was no significant difference between height SDS for bone age at the beginning and end of observation in either treated or untreated groups. No significant relationship between the mean dose of cyproterone acetate used and change in height SDS for bone age could be determined. We conclude that cyproterone acetate has no beneficial effect on the growth prognosis of children with central precocious puberty.Abbreviation GnRH gonadotrophin releasing hormone     

Treatment of short stature in renal disease with recombinant human growth hormone.

Six prepubertal children with chronic renal failure (group 1), six prepubertal children with renal transplants (group 2), and six pubertal children with renal transplants (group 3) who were short (mean height SD score, -3.2, range -4.5 to -1.6) and growing poorly (mean (range) growth velocity (cm/year) over the year before treatment: group 1, 4.8 (3.5-5.8), group 2, 2.3 (0.9-4.7), and group 3, 3.2 (0.5-6.5] were treated with recombinant human growth hormone 30 units/m2/week in daily doses for a median of 0.98 years (range 0.25-0.99). Mean (range) growth velocity over the treatment period increased significantly in all groups (group 1, 10.7 (8.8-12.3), group 2, 6.1 (2.7-10.8), and group 3, 6.0 (4.6-6.8]. There was, however, no improvement in height SD score for bone age in any group. The renal function of two children deteriorated after starting treatment with growth hormone, but it was not possible to say whether the growth hormone was responsible for this. The long term effects of treatment and its influence on final height are not yet known.     

Oxandrolone in Girls with Turner's Syndrome

Twenty-six one-year treatment periods on oxandrolone (0.1 mg/kg/day) were studied in 20 patients with Turner's syndrome. Control patients with Turner's syndrome were matched by using the following criteria: difference in bone age being not greater than 0.S years and difference in the Bayley-Pinneau height prediction not greater than 3 cm. Height and height velocity were compared with standards of girls with Turner's syndrome (10) and expressed in standard deviation scores (SDS). On oxandrolone height velocity increased significantly from −0.3 SDS to +3.0 SDS. The increase in height velocity was negatively correlated to the bone age at onset of treatment ( r = 0.62, p<0.01). Height SDS improved by 0.45 SDS in the treated patients whereas it did not change in the control patients. The bone age velocity during the treatment period (including a six-month period after treatment) was 0.75 year/year in the treated, compared to 0.66 year/year in the control patients (NS). 15 of the 20 patients have reached final height. The difference in final height minus predicted height (Bayley-Pinneau) at onset of treatment was taken as a measure of "gain in final height". Seven of those (mean bone age 12.1 years at onset of treatment) were treated for one year only and had–compared to the matched controls–a mean net gain in final height of 2.5 cm (NS). Eight patients (mean bone age 10.1 years at onset of treatment) were treated for two one-year periods and had a significant mean net gain in final height of 5.2 cm. Height predictions calculated by the method of Lenko (14) gave an identical mean net gain in final height (5.1 cm)     

Recombinant human growth hormone treatment in infants with chronic renal failure

Poor growth is a particular problem for children with congenital renal disease. A one year trial of the use of recombinant human growth hormone (rhGH) in eight infants and young children with chronic renal failure is reported here. At entry bone age was less than 2 years, mean (range) chronological age 1.9 (1.3-2.7) years, and glomerular filtration rate (GFR) was 17 (9-42) ml/min/1.73 m2. Height standard deviation score (SDS) was -3.3 (-4.6 to -2.0) and height velocity SDS was -1.3 (-3.1 to 0.7). One child was withdrawn when he received a renal transplant after 9.5 months. Two children required dialysis, but remained in the trial. Treatment with rhGH resulted in an increase in height SDS to -2.2 (-4.2 to -0.9), p = 0.0002, and height velocity SDS to 1.1 (-0.7 to 2.6), p = 0.006. There was no change in GFR and no serious adverse events. There was no effect on plasma lipids, calcium, phosphate, intact parathyroid hormone, or glucose. Alkaline phosphatase rose significantly. Thus rhGH improved growth in eight infants with chronic renal failure, with four children entering the normal range.     

Growth in pre-pubertal children with myelomeningocele (MMC) on growth hormone (GH): the KIGS experience

PURPOSE: To analyse the auxological data of children with myelomeningocele (MMC) on growth hormone (GH) therapy whose growth data was documented within KIGS (Pfizer International Growth Database). Longitudinal growth data of a sub-group of pre-pubertal children were studied after a treatment period of 3 years. PATIENTS AND METHODS: Eighty patients (38 m, 42 f) with MMC with a median chronological age (CA) of 11.6 years (at latest visit) on GH were registered in the KIGS database. In 52 patients, GH deficiency was documented. GH therapy started with a median dose of 0.23 mg kg(-1) per week. The 3-year longitudinal growth was analysed in 21 patients (13 m, 8 f; median CA 9.2 years, latest visit), all of whom were pre-pubertal at start and during GH therapy. RESULTS: GH therapy started at 7.5 years with a dose of 0.23 mg kg(-1) per week. Birth length SDS (-0.51) and mid-parental height SDS (+0.07) were in the normal range. BMI SDS at start was +0.24, at latest visit -0.03. After a median treatment duration of 3.0 years (latest visit), height SDS improved from -2.97 (start of GH) to -2.01. The sub-group of pre-pubertal MMC patients started GH therapy (dose 0.22 mg kg(-1) per week) at 6.2 years. Growth velocity (GV) SDS increased significantly (at start: -1.77; 1 year: +2.60, 2 years: +2.25, 3 years: +1.24), thus height SDS improved from -3.25 at start to -1.87 at 36 months. BMI SDS was in the normal range and remained unchanged during GH therapy. No major side effects of GH were recorded. CONCLUSION: GH had positive effects on height SDS in MMC patients. The analysis of the longitudinal growth data of pre-pubertal MMC patients showed a significant increase in GV SDS and improvement of height SDS.     

Prediction of the growth response of short prepubertal children treated with growth hormone

The aim of this study was to identify predictors of the growth response to growth hormone (GH) during the first 2 years of GH treatment, using auxological data and the maximum GH response (GH_max) to provocation tests. The patients were 169 prepubertal short children (27F, 142M), with Gmax values ranging from 0 to 65 mU/1. Their mean age (± SD)was8.3 ± 2.4 years (range 3-13 years), mean height SDS –3.0 ± 0.7 (range –1.5 to –6.0SDS) and mean pretreatment height velocity was normal (± 0.0 SDS) (range -1.6 to + 0.9 SDS). The increase in height SDS during the first 2 years of GH treatment (0.1 U/kg/day) varied from 0.10 to 3.75 SDS, with younger children having a better growth response. Individual growth responses correlated (p < 0.001) with GH_max (r =–0.37), age (r= -0.35), 1-year pretreatment delta SDS (r = -0.25), mid-parental height SDS (r = 0.34), height SDS at start of treatment (r =–0.22) and difference between height SDS of an individual child at the onset of GH treatment and mid-parental height expressed in SDS (diff SDS) (r = –0.43). In a multiple stepwise linear regression model, diff SDS and log GH_max were found to be the strongest predictors of the magnitude of the growth response. In the short children in this study who exhibited a broad range of GH_max values, 33% of the growth response during the first 2 years of treatment could be predicted.