Impact of CNS Stimulants for Attention-Deficit/Hyperactivity Disorder on Growth: Epidemiology and Approaches to Management in Children and Adolescents.

Central nervous system stimulants are established treatments for pediatric attention-deficit/hyperactivity disorder with robust efficacy data. Reductions in appetite, weight, and growth velocity are some of the most common concerns regarding the long-term use of central nervous system stimulants in developing children. They are associated with suppression of weight and body mass index in childhood. However, both weight and body mass index often progressively increase over adolescence at rates faster than those seen in non-attention-deficit/hyperactivity disorder youth to the degree that attention-deficit/hyperactivity disorder is associated with elevated body mass index by the end of adolescence regardless of medication use. The capacity of central nervous system stimulants to slow growth was identified 50 years ago. Recent work has established that the growth deficits accumulate during the first 2 years of use and may persist provided medication is used. Early initiation coupled with persistent use through adolescence is most likely to be associated with clinical impactful growth suppression. There has been limited formal investigation of treatments for stimulant-associated reductions in weight and height. The most robust evidence exists for drug holidays improving weight gain. Observational studies suggest that limiting lifetime exposure or discontinuing medication is associated with greater adult height. Additional research is needed to identify the causal mechanisms driving the observed slowing in growth as well as the identification of predictors of clinically impactful growth suppression.

The concentration of selected elements in the placenta according to selected sociodemographic factors and their effect on birth mass and birth length of newborns.

BACKGROUND AND AIMS: The placenta is a remarkable organ which provides critical transport functions between the maternal and fetal circulations during pregnancy. The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals, such as calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese, determines the correct growth and development of a fetus. The aim of the study was to assess the concentration of selected elements in the placenta, and to assess the impact of their concentrations on the birth weight and birth length of newborns. The second aim of the study was to assess the influence of selected sociodemographic factors on the concentration of elements in the placenta. RESULTS: The study demonstrated that the age of mothers affected the concentration of Ca and Mn in the placenta, and their habit of tobacco smoking during the gestational period was associated with higher concentrations of Ca, P, K, Mg, Fe, Cu, and Cd in the placental tissue. The results also showed that concentrations of K, Fe, Zn, and Mn in the placental tissue affected birth length. Furthermore, the association was demonstrated between a higher Cd concentration in the placenta (≥ 0.0503 µg/g) and the birth anthropometric parameters of neonates. CONCLUSIONS: Smoking during pregnancy and environment pollution are the factors that affects the concentration of elements in the placenta and contributes to their high accumulation in the placenta. Smoking during pregnancy causes an increased concentration of cadmium in the placenta which has negative health effects for the newborn. Women living in a big city or village had a higher concentration of cadmium in their placentas compared to women living in smaller cities. The significant influence of some elements (K, Fe, Zn, Cu and Cd) on the newborn's birth parameters was also demonstrated. The results of our research indicate the importance of the mother's lifestyle in providing the placenta with elements, which affects the growth of the fetus.

Metabolic and immunological assessment of small-for-gestational-age children during one-year treatment with growth hormone: the clinical impact of apolipoproteins.

Children born small for gestational age (SGA) are at a higher risk for metabolic disorders later in life. In this study, we aimed to characterize young SGA children without catch-up growth and evaluate the effects of GH treatment on endocrinological, metabolic, and immunological parameters. Study design is a one-year single hospital-based study included prospective observation of SGA patients during 12 months of GH treatment. Clinical and laboratory profiles of SGA children at baseline were compared with controls born appropriate size for age. Twenty-six SGA children (median age, 3.4 years) and 26 control children (median age, 3.8 years) were enrolled. Anthropometric, hematologic, biochemical, immunological, and endocrinological parameters were assessed at baseline and 1, 3, 6, 9, and 12 months after the start of GH treatment. As a result, median height SD score (SDS) of SGA children increased by +0.42 with 12-month GH treatment. Body mass index SDS was lower in SGA children than in controls. Serum apolipoprotein A1 increased, whereas apolipoprotein B decreased during GH treatment. Serum leptin and resistin levels, which were lower in SGA children than in controls at baseline, did not change remarkably with GH treatment. Monocyte counts, which were lower in SGA patients at baseline, increased after GH treatment. Neutrophil counts significantly increased after GH treatment. Natural killer cell ratios, which were higher in SGA patients, decreased after GH treatment. In conclusion, there was no evidence suggesting metabolic abnormalities in SGA children. Serum apolipoprotein changes might predict the beneficial role of GH treatment in lowering cardiometabolic risk.

Resting energy expenditure in girls with Turner syndrome.

BACKGROUND: Knowledge concerning energy metabolism in Turner syndrome (TS) is lacking. We compared the resting energy expenditure per fat-free mass (REE/FFM) in TS with other girls with short stature treated with growth hormone (GH) and age-related controls. METHODS: We measured prospectively REE by spirometry under fasting conditions in the morning in 85 short prepubertal girls at the start of GH treatment. Diagnoses were TS (n=20), GH deficiency (GHD) (n=38) and small for gestational age (SGA) short stature (n=27). Additionally, 20 age-related controls were studied. Mean ages were 8.3 (TS), 7.1 (GHD), 6.9 (SGA) and 8.5 years (controls). Mean heights were -2.90 (TS), -3.32 (GHD), -3.69 (SGA) and -0.03 standard deviation scores (SDS) (controls). FFM was measured by bioelectrical impedance analysis (BIA). RESULTS: At the start of GH girls with TS showed insignificantly higher REE per FFM (REE/FFM) (mean±SD; 65±9 kcal/kg×day) than did the other female patients (62±9 kcal/kg×day) (p>0.23). The healthy controls had significantly lower REE/FFM (35±4 kcal/kg×day) (p<0.001). Follow-up examination of the patients after 6 or 12 months revealed decreasing REE/FFM in TS (62±9 kcal/kg×day) resulting in comparable REE/FFM in all three patient groups. CONCLUSIONS: At baseline short girls with TS had insignificantly higher REE/FFM than short children with SGA or GHD, but in follow-up this difference was not detectable any more. Future studies are necessary to understand this observation.

A 4-Year, Open-Label, Multicenter, Randomized Trial of Genotropin® Growth Hormone in Patients with Idiopathic Short Stature: Analysis of 4-Year Data Comparing Efficacy, Efficiency, and Safety between an Individualized, Target-Driven Regimen and Standard Dosing.

BACKGROUND/AIMS: Growth hormone (GH) treatment regimens for children with non-GH-deficient, idiopathic short stature (ISS) have not been optimized. To compare the efficacy, efficiency, and safety of an individualized, target-driven GH regimen with standard weight-based dosing after 4 years of treatment. METHODS: This is a 4-year, open-label, multicenter, randomized trial comparing individualized, formula-based dosing of Genotropin® versus a widely used ISS dose of Genotropin®. Subjects were prepubertal, had a bone age of 3-10 years for males and 3-9 years for females, were naive to GH treatment, and had a height standard deviation score (Ht SDS) of -3 to -2.25, a height velocity <25th percentile for their bone age, and peak stimulated GH >10 ng/ml. After the first 2 years, the individualized-dosing group was further randomized to either 0.18 or 0.24 mg/kg/week. RESULTS: At 4 years, subjects in all treatment regimens achieved similar average height gains of +1.3 SDS; however, the individualized dosing regimen utilized less GH to achieve an equivalent height gain. CONCLUSION: Individualized, formula-based GH dosing, followed by a dose reduction after 2 years, provides a more cost-effective growth improvement in patients with ISS than currently employed weight-based regimens.

Aldehyde dehydrogenase 2-a potential genetic risk factor for lung function among southern Chinese: evidence from the Guangzhou Biobank Cohort Study.

PURPOSE: In Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function. METHODS: We examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1 second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression. RESULTS: ALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1 second -1.52%, 95% confidence interval [CI], -2.52% to -0.51% for one inactive allele and -2.05%, 95% CI, -3.85% to -0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacity -1.25%, 95% CI -2.15% to -0.35% and -1.65%, 95% CI, -3.25% to -0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders. CONCLUSIONS: Previous findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease.

Parent preference in Switzerland for easy-to-use attributes of growth hormone injection devices quantified by willingness to pay.

Sustained treatment adherence, usually over long periods of time, is critical to the success of growth hormone (GH) therapy. However, adherence rates are often poor which may result in suboptimal clinical outcomes. The type of device used by patients to administer their GH can influence adherence. Offering patients a choice of device maximizes the chance of adherence to treatment. Multiple factors will influence a patient's choice of device, depending on individual priorities. This study evaluated the most preferred features of GH injection devices by parents using a web-based questionnaire and as assessed by their willingness to pay for specific device features. The results show that parents are willing to pay for device features facilitating ease of use.

Translating clinical guidelines into practice: the effective and appropriate use of human growth hormone.

There are 9 recombinant human growth hormone (rhGH) products currently available for 10 US Food and Drug Administration-approved indications; each rhGH product is approved for 1 or more indications. Adult and pediatric patients with the various conditions for which rhGH is indicated, from idiopathic short stature (ISS) and growth hormone (GH) deficiency to short bowel syndrome and HIV/AIDS wasting, may benefit from rhGH treatment. In clinical practice, pediatric patients with GH deficiency or ISS make up the majority of the population receiving treatment with rhGH. Most rhGH products are provided through specialty pharmacies that often have to balance the needs of the patient, their own utilization objectives, and the availability of the rhGH on formulary from a particular payer. Often, a payer will prefer only 2 or 3 rhGH products to cover all 10 indications. As such, managed care professionals need to be more informed about the options available and should be familiar with the different indications to help educate patients about treatment. Additionally, healthcare providers should endeavor to identify and manage the care of appropriate patients who would potentially benefit from rhGH therapy, and should be aware of formulary options. Because many of the patients are children and young adults, adherence to treatment is a concern; patient education on the importance of treatment adherence should be ongoing. Various mechanisms are in place (eg, prior authorization requirements and case manager follow-up) to help ensure that rhGH products are used, and used appropriately. This publication includes highlights from a roundtable discussion by key opinion leaders (clinicians and managed care professionals) on how managed care policies and clinical guidelines on appropriate use of rhGH translate into real-world practice. Also discussed are the efficacy and safety of rhGH therapy for its pediatric indications, and the role of specialty pharmacies in managing patient access to therapy.

Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation.

PURPOSE: Children with acute lymphoblastic leukemia (ALL) are at risk for impaired bone accrual. This peripheral quantitative computed tomography study assessed changes in bone mineral density (BMD) and structure after completion of ALL treatment. METHODS: Fifty ALL participants, ages 5-22 yr, were enrolled within 2 yr (median 0.8 yr) after completing ALL therapy. Tibia peripheral quantitative computed tomography scans were performed at enrollment and 12 months later. Age-, sex-, and race-specific Z-scores for trabecular BMD (TrabBMD), cortical BMD (CortBMD), and cortical area (CortArea) were generated based on more than 650 reference participants. Multivariable linear regression models examined determinants of changes in Z-scores. RESULTS: At enrollment, mean TrabBMD (-1.03±1.34) and CortBMD (-0.84±1.05) Z-scores were low (both P<0.001) compared with reference participants. TrabBMD and CortBMD Z-scores increased to -0.58±1.41 and -0.51±0.91 over 1 yr, respectively (both P<0.001). Changes in cortical outcomes varied according to the interval since completion of therapy. Among those enrolled less than 6 months after therapy, CortArea Z-scores increased and CortBMD Z-scores decreased (both P<0.01). Among those enrolled 6 months or more after therapy, CortArea Z-scores did not change and CortBMD Z-scores increased (P<0.01). Changes in CortArea and CortBMD Z-scores were inversely associated (r=-0.32, P<0.001). Cumulative glucocorticoid exposure, leukemia risk status, and antimetabolite chemotherapy were not associated with outcomes. CONCLUSION: TrabBMD was low after completion of ALL therapy and improved significantly. Early increases in cortical dimensions were associated with declines in CortBMD; however, participants further from ALL therapy demonstrated stable cortical dimensions and increases in CortBMD, potentially reflecting the time necessary to mineralize newly formed bone.

Efficacy of long-term growth hormone therapy in short children with reduced growth hormone biological activity.

AIM: The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated. METHODS: In 12 GH-deficient (GHD) and 12 bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio. RESULTS: We found a significant (p < 0.05) increase in growth velocity in both groups during the first year of GH treatment (non- GHD: from -1.7 to 5.4 SDS; GHD: from -1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28 ± 653.15 euro) and bioinactive GH children (1639.55 ± 631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68 ± 2018.1 euro) and bioinactive GH children (11355.08 ± 1747.61 euro). CONCLUSION: In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.

Cost-effectiveness of somatropin for the treatment of short children born small for gestational age.

BACKGROUND: Short children born small for gestational age (SGA) may be at increased risk for long-term morbidity and reduced health-related quality of life (HRQoL) due to their short stature. Normalization of height in childhood and adolescence is possible in such children via the use of the recombinant human growth hormone somatropin. OBJECTIVE: The aim of this study was to determine whether somatropin was a cost-effective treatment option in short children born SGA. METHODS: A decision analytic model was constructed to calculate the cost-effectiveness of somatropin treatment versus no treatment over the lifetime of a short individual born SGA, from the perspective of the UK National Health Service (NHS). The model was based on patient-level data from a multicenter, double-blind, randomized controlled trial that reported the effects of somatropin on final (adult) height in short children born SGA. Health care resource and drug costs associated with each of the treatment arms were considered, and published utility scores were used to calculate improvement in HRQoL. The model calculated incremental costs and incremental quality-adjusted life-years (QALYs) associated with somatropin treatment compared with no treatment. Cost-effectiveness was expressed as incremental cost per QALY and cost per centimeter of height gained. RESULTS: Over a patient's lifetime, somatropin (0.033 mg/kg/d) treatment was associated with a height gain of 16.12 cm and a cost per centimeter of height gained of pound4359 compared with no treatment. The incremental cost of somatropin treatment was pound70,263, with a QALY gain of 2.95, resulting in an incremental cost per QALY of pound23,807-below the widely accepted cost-effectiveness threshold in the United Kingdom of pound30,000. CONCLUSION: In this model, somatropin was a cost-effective treatment option for short children born SGA from the perspective of the UK NHS.

Active malaria morbidity management has limited impact on height status of preschool Senegalese children.

Although infections contribute to growth faltering in preschool children, malaria prevention seems to have limited impact on height status. In 2002-2003, a malaria intermittent preventive treatment (IPT) trial was conducted in Senegal, including randomly selected preschool children from 11 villages. A rapid decrease in stunting prevalence (from 28.3 to 16.3%; P < 0.0001) was reported in both intervention and placebo groups. During this 15-mo period, both groups of children benefited from active detection and prompt treatment of malaria attacks. In this study, we investigated whether management of malaria morbidity could explain the improvement of height status. An anthropometric survey, conducted in September 2004 in the area, included 929 2- to 5-y-old children. Some 539 children, previously included in the 2002-2003 IPT trial, benefited from active malaria morbidity management and formed the malaria trial group. The remaining 390 children constituted the control group. Mean height-for-age and stunting prevalence in September 2004 were compared between groups adjusting for age and mother's activity. Mean height-for-age Z-scores did not differ between trial (-1.17 +/- 0.93) and control children (-1.24 +/- 1.00; P = 0.25). Only 36- to 47-mo-old malaria trial children had a lower prevalence of stunting than controls of similar age (19.4 vs. 28.7%; P = 0.044). Compared with the usually slow progression of height status related to better living conditions, it seems very likely that the rapid improvement observed among IPT study children resulted from the trial. These findings suggest that improved health services provided by the trial may also have benefited children not included living in study villages.

Mecasermin: new drug. Insufficient improvement in statural growth.

(1) Human insulin-like growth factor type 1 (IGF-1) is the main effector of growth hormone action. Primary IGF-1 deficiency is a rare disease, mainly resulting in very short stature; (2) Mecasermin is a recombinant IGF-1 marketed for this indication as a twice daily subcutaneous injection; (3) Clinical evaluation is mainly based on a non-comparative follow-up study of 76 children with an average age of 7 years, some of whom were treated for 8 years. The mean height at treatment initiation was 6.7 standard deviations below normal. Eight years later, it was 5.2 standard deviations below normal, i.e. their growth failure remained very severe; (4) The main short-term adverse effects of mecasermin are hypoglycaemia, headache and intracranial hypertension. Nearly one in 5 children developed tonsillar hypertrophy, resulting in otitis and hypoacusis; (5) Animal studies showed hypertrophy of other organs (kidneys, spleen and heart) as well as carcinogenic effects. The risk in humans is unknown; (6) The mecasermin packaging is not well-adapted (a multidose vial designed to be punctured several times), and is a potential source of contamination and errors. Prefilled pens or syringes would be easier to use; (7) In practice, the limited clinical benefits of mecasermin do not justify exposure to its potential risks.

Growth-attenuation therapy: principles for practice.

Publication of an account of growth attenuation with high-dose estrogen in a child with profound physical and cognitive disability brought widespread attention to a common and complex issue faced by families caring for similarly affected children, namely, the potentially negative effect of the increasing size of a child on the ability of his or her family to provide independent care, which in turn makes it more difficult for parents to keep the child in the home and involved in family activities. In this article we explore the scientific rationale for, effectiveness and safety of, and ethical considerations bearing on growth-attenuation treatment of children with profound and permanent cognitive disability. Informed responses to key clinically relevant questions are proposed. Our analysis suggests that growth attenuation is an innovative and sufficiently safe therapy that offers the possibility of an improved quality of life for nonambulatory children with profound cognitive disability and their families. Pediatricians and other care providers should include discussion of these options as part of anticipatory guidance around the age of 3 years so that, if elected, potential clinically meaningful benefits of growth-attenuation therapy can be realized. Because of the publicity and debate surrounding the first reported case, ethics consultation is recommended.

Effects of micronutrients on growth of children under 5 y of age: meta-analyses of single and multiple nutrient interventions.

BACKGROUND: Micronutrient interventions have received much attention as a cost-effective and promising strategy to improve child health, but their roles in improving child growth remain unclear. OBJECTIVE: Meta-analyses of randomized controlled trials were conducted to evaluate the effect of micronutrient interventions on the growth of children aged <5 y old. DESIGN: Eligible studies were identified by PubMed database searches and other methods. Weighted mean effect sizes and 95% CIs were calculated for changes in height, weight, and weight-for-height z scores (WHZ) by using random-effect models. Tests for publication bias were done by using funnel plots, heterogeneity, and stratified analyses by predefined characteristics. RESULTS: Interventions including iron (n = 27) or vitamin A (n = 17) only had no significant effects on growth. Interventions including zinc only (n = 43) had a small positive effect (effect size = 0.06; 95% CI: 0.006, 0.11) on change in WHZ but no significant effect on height or weight gain. Multiple micronutrient interventions (n = 20) improved linear growth (0.09; 95% CI: 0.008, 0.17). CONCLUSIONS: Our findings confirm earlier results of no benefits for interventions including iron and vitamin A only but differ from the earlier meta-analysis that found improvements in linear growth for zinc only interventions. This may be due to the improved nutritional status of children in the more recent studies. Multiple micronutrient interventions improve linear growth, but the benefits are small. Other strategies are needed to prevent stunting.

[GH treatment in patients with idiopathic short stature]. / Uso de GH em pacientes com baixa estatura idiopática.

Growth hormone has been used in the treatment of patients with idiopathic short stature. Clinical and laboratory criteria are discussed, taking into consideration the indication of GH and the evaluation of its efficacy and individual responsiveness. Anthropometric, psychosocial, ethical, and also cost/benefit aspects must be considered before GH prescription in idiopathic short stature patients.

Uso de GH em pacientes com baixa estatura idiopática: [revisão] / GH treatment in patients with idiopathic short stature: [review]

Pacientes com baixa estatura idiopática podem ser tratados com GH. Os critérios clínicos e laboratoriais utilizados na decisão do uso do GH, bem como no reconhecimento da responsividade dos indivíduos ao tratamento, são discutidos. Não apenas os resultados antropométricos, mas também os aspectos éticos e psicossociais devem ser considerados na avaliação dos custos/benefícios envolvidos no tratamento com GH em pacientes com baixa estatura idiopática.

Growth hormone has been used in the treatment of patients with idiopathic short stature. Clinical and laboratorial criteria are discussed, taking into consideration the indication of GH and the evaluation of its efficacy and individual responsiveness. Anthropometric, psychosocial, ethical, and also cost/benefit aspects must be considered before GH prescription in idiopathic short stature patients.

A longitudinal assessment of the effect of inhaled fluticasone propionate therapy on adrenal function and growth in young children with asthma.

OBJECTIVE: Fluticasone proprionate (FP) is increasingly used to treat very young children with asthma. Its safety in terms of effects on the hypothalamic pituitary axis (HPA) and growth in this age group is uncertain. PATIENTS AND METHODS: Eleven children (median (range) age 10 (5.6-24.3) months) presenting with recurrent wheeze and family history of asthma were studied prospectively for a period of 18 months. Children received daily-inhaled FP 250 microg via a spacer device. No other corticosteroid therapy was administered prior to or during the study. A Short Standard Synacthen Test (SST) (125 microg) was performed pretreatment, and after 6 and 18 months. Weight (Wt), height (Ht), and body mass index (BMI) were measured at 3-6 monthly intervals. RESULTS: Fasting early morning and peak cortisol levels remained within the normal reference range with therapy. There were no changes in Ht SDS, whereas both Wt SDS (baseline 0.05 (-2.17 to 0.52) vs. +18 months 0.68 (-0.5 to 1.36) P < 0.02) and BMI SDS (-0.22 (-1.73 to 0.75) vs. 0.86 (0.03 to 1.99) P < 0.005) increased after 18 months of treatment. CONCLUSION: Daily treatment with inhaled FP 250 microg in young children with asthma appears to have no adverse effects on the HPA or on linear growth, however, treatment is associated with increases in body Wt and BMI in young children.

Assessment of the long-term safety of inhaled ciclesonide on growth in children with asthma.

OBJECTIVE: To assess the effects of the new inhaled corticosteroid ciclesonide on growth in children with asthma. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled study to assess the effects of inhaled ciclesonide on growth in children with mild, persistent asthma. After a 6-month run-in period, 661 prepubertal children who were aged 5.0 to 8.5 years were randomly assigned to once-daily morning treatment for 1 year with ciclesonide 40 or 160 microg (ex-actuator) or placebo, followed by a 2-month follow-up period. The primary end point was the linear growth velocity (linear regression estimate) over the double-blind treatment period. Growth was recorded as the median of 4 stadiometer measurements. Adverse events and 10-hour overnight and 24-hour urinary free cortisol levels were also assessed. RESULTS: Mean linear growth velocity during run-in was comparable between groups: 160 microg, 6.20 cm/year; 40 microg, 6.59 cm/year; placebo, 6.49 cm/year. Mean differences from placebo (5.75 cm/year) in growth velocity over the double-blind treatment period were -0.02 cm/year for ciclesonide 40 microg and -0.15 cm/year for ciclesonide 160 microg. Both ciclesonide treatments were noninferior to placebo with respect to growth velocity. The overall incidence of adverse events was comparable between groups, and no significant changes in 10-hour overnight or 24-hour urinary free cortisol levels were noted between groups during the double-blind treatment period. CONCLUSIONS: Ciclesonide demonstrated no detectable effect on childhood growth velocity, even at the highest dosage, which may ease concerns about systemic adverse events.