Differences In Growth Velocity Research Articles

Twice Daily Compared to Three Times Daily Hydrocortisone in Prepubertal Children with Congenital Adrenal Hyperplasia

Introduction: Glucocorticoid therapy in children with congenital adrenal hyperplasia (CAH) must be finely balanced between optimizing adrenal control and minimizing side effects. Twice (BID) rather than three times daily (TID) hydrocortisone may provide similar adrenal control and reduce metabolic risk. We compared BID and TID regimens with respect to adrenal control, growth, and metabolic effects. Methods: A retrospective chart review (n = 128 visits, 36 individual patients) of prepubertal children with classical CAH was conducted at a tertiary care center between March 2007 and February 2020. Adrenal control, growth, and metabolic data were extracted in those taking hydrocortisone BID versus TID. Univariate generalized estimating equations models were performed to analyze the effect of dose frequency on outcomes of interest. Results: Overall, we found no difference in adrenal control (8% vs. 18% poor control) or testosterone levels (9.65 ng/dL vs. 7.62 ng/dL) between the BID versus TID groups. We detected no difference in growth velocity (6.86 vs. 6.32 cm/year) or bone age advancement (11.3 vs. 5.91 months) between the groups. There was no difference in daily steroid dose (12.1 vs. 11.7 mg/m²/day), BMI Z-score (0.43 vs. 0.31), or systolic blood pressure percentile (65.5 vs. 61.7). Conclusion: BID dosing provides similar adrenal control and does not appear to impact growth or bone age advancement. On the other hand, TID dosing does not appear to increase the metabolic side effect profile in this age-group. Dosing should be patient-centered with individualized consideration.

Effect of an exclusive human milk diet on feeding tolerance in preterm infants

To compare the time to full enteral feeds in preterm infants fed exclusive human milk (EHM) - mother's own milk (MOM) fortified with human milk-based fortifier (HMBF), to those who received partial human milk (PHM) - MOM fortified with bovine milk-based fortifier (BMBF), and exclusive formula. A single-center retrospective study of infants with birth weight <1250 g from 2013 to 2018. Data on feeding, growth and other short-term neonatal morbidities were collected. On regression analysis, time to full enteral feeds was significantly higher in PHM compared to EHM group (β-coefficient 4.14, 95% CI 0.00-8.29) and formula-fed group compared to EHM (β-coefficient 4.3, 95% CI 0.32-8.20). No significant differences in growth velocity, length of stay and other morbidities were found between the groups. Infants in EHM had better feeding tolerance and reached their enteral feed goals sooner compared to PHM and formula-fed groups.

Risk Factors for Rebound After Correction of Genu Valgum in Skeletal Dysplasia Patients Treated by Tension Band Plates.

Growth modulation using tension band plates (TBPs) is increasingly important for lower limb deformity correction in patients with skeletal dysplasia (SKD). Development of rebound deformity is a concern after TBP removal. Data regarding this complication are rare; therefore, we evaluated the prevalence and risk factors for rebound deformity in children with SKD undergoing correction of genu valgum using TBP. All patients with SKD with genu valgum treated by TBP at the distal femur or/and proximal tibia at a single center were reviewed. Inclusion criteria were: (1) minimum 2-year follow-up after TBP removal or having revision surgery for rebound deformity and (2) implant removal age for girls 14 years and below and boys 16 years and below. Exclusion criteria were any femoral/tibial osteotomies during TBP treatment or follow-up. A change of ≥3 degrees of mechanical lateral distal femoral and/or medial proximal tibial angle was accepted as rebound deformity and analyzed statistically. Thirty-three patients (59 limbs; 52 femur and 29 tibia physes) met our criteria. Mean follow-up after implant removal was 43.7 months. Rebound deformities were seen in 43 limbs (39 femurs and 13 tibias). Boys had more rebound than girls; however, this was not influenced by body mass index. Femurs had more rebound than tibias. Patients in the rebound group were younger than the nonrebound group. Time from application to removal of TBP was shorter in the rebound versus nonrebound group. Overcorrected limbs had more rebound deformity than not overcorrected. The difference in growth velocity of lower limbs in the rebound versus nonrebound group was statistically significant. Patients with epiphyseal dysplasia had more rebound than metaphyseal dysplasia, but this was not statistically significant. Risk factors for developing a rebound deformity after correction of genu valgum using TBP in SKD included male sex, TBP surgery at a young age, short duration of TBP implantation, overcorrected extremity (mechanical axis deviation ≤1), and high percent growth velocity after TBP removal. Level IV-retrospective study.

Effectiveness of growth hormone therapy in children with Noonan syndrome.

PurposeRecombinant human growth hormone (rhGH) has been used to improve growth in children with Noonan syndrome (NS). This study aimed to investigate the efficacy of rhGH therapy in Korean children with NS.MethodsSeventeen prepubertal children (10 boys, 7 girls) with NS who received rhGH therapy for at least 3 years between 2008 and 2017 were included. To compare the response, age- and sex-matched children with GH deficiency (GHD; n=31) were included. Height and growth velocity before and during treatment were analyzed.ResultsThe mean age of NS patients was 6.34±2.32 years. After treatment, the height standard deviation score (SDS) increased from -2.93±0.81 to -1.51±1.00 in patients with NS and from -2.45±0.42 to -1.09±0.47 in patients with GHD. There were no significant differences in growth velocity or change in height SDS between patients with NS and GHD. Growth velocity in the first year of treatment was higher in patients with PTPN11 mutations than those without PTPN11 mutations, but the change in height SDS was not significantly different between those 2 groups.ConclusionsrhGH therapy can increase linear growth in prepubertal children with NS. The growth response between patients with NS and patients with GHD was not significantly different. Furthermore, we observed that lower doses of growth hormone have a similar effect on height compared to previous studies in patients with NS. Our study indicates that rhGH treatment is useful for growth promotion.

Direct growth of 2D MoO2 single crystal on SiO2/Si substrate by atmospheric pressure chemical vapor deposition

Due to its distinct properties, two-dimensional (2D) materials had attracted much attention and plenty of 2D materials had been synthesized and studied. Metal oxides have been widely used in lithium-ion battery, supercapacitor, catalyst, etc, but the corresponding 2D material of metal oxides has not been sufficiently researched. Here, micrometer-scale 2D Molybdenum dioxide (MoO2) single crystals have been successfully synthesized directly on silicon dioxide/silicon (SiO2/Si) substrate by atmospheric pressure chemical vapor deposition, through the reduction by hydrogen. The growth temperature is 690 °C, and the reduction reaction lasted with 90 minutes. Raman spectra and x-ray photoelectronic spectroscopy are used to confirm the chemical component of MoO2. The shape of two-dimensional MoO2 single crystals has three types, including standard parallelogram, parallelogram with two angles misses and hexagonal. The growth model of three shape types is discussed, and the difference in growth velocity between two growth directions is the key factor of the final shape. The theoretical calculation confirmed the metallic property of as-synthesized 2D MoO2 and its resistivity is 2 × 10−4 Ω*cm, indicating it has excellent conductivity and may have potential application for conducting films.

Effect of -202 A/C IGFBP-3 polymorphisms on growth responses in children with idiopathic short stature.

PurposeThis study evaluated the -202 A/C insulin-like growth factor binding protein 3 (IGFBP-3) promoter polymorphism as a predictor of serum IGFBP-3 concentration and growth velocity after recombinant growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS).MethodsGenotyping and serial measurement of clinical parameters were performed in 69 children with a confirmed diagnosis of ISS. Restriction fragment length polymorphism analysis was performed to determine the genotype at the -202 IGFBP-3 locus. Serum insulin-like growth factor 1 (IGF-1) and IGFBP-3 levels were measured at baseline and after 1 year of rhGH treatment, as were height standard deviation score and growth velocity.ResultsThe -202 A/C IGFBP-3 genotype comprised 69.6% AA, 24.6% AC, and 5.8% CC. One year of treatment did not produce a meaningful difference in IGF-1 or IGFBP-3 levels between children in the AA group and those with at least one copy of the C allele (AC/CC group). Comparing the 2 groups after one year also revealed no significant difference in growth velocity (ΔHeight: 9.061±1.612 cm/yr in the AA group, 9.421±1.864 in the AC/CC group, P=0.419).ConclusionsrhGH treatment was effective and there were no significant differences in IGF-1, IGFBP-3, or growth velocity according to genotype. Thus, -202 IGFBP-3 genotype may not be a major factor affecting individual growth responses in Korean children with ISS.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Growth and Clinical Outcome in Very Low-Birth-Weight Infants After the Introduction of a Multicomponent Intravenous Lipid Emulsion.

Very low-birth-weight (VLBW; birth weight < 1500 g) infants are often dependent on intravenous nutrition after birth. Conventional soy-based intravenous lipid emulsions (Soy LE) are associated with inflammatory and metabolic complications that may be harmful to preterm infants. Evidence to support any clinical benefit associated with newer multicomponent emulsions (Mixed LE), remains inconsistent and unsubstantiated in appropriate studies. This retrospective study aimed to determine whether growth and clinical outcomes differed between VLBW infants given Mixed LE vs Soy LE at Auckland City Hospital. Data were collected on nutrition, growth, and neonatal morbidities for the first 4 weeks after birth. Outcomes were compared between 2 lipid cohorts, Soy LE (February 2013 - August 2014) and Mixed LE (August 2014 - December 2015), using univariate and multivariate analysis. 207 infants (Soy LE, 105 vs Mixed LE, 102) were included in the study. Significantly fewer infants in the Mixed LE cohort developed any stage retinopathy of prematurity (Soy LE 59% vs Mixed LE 39%, P=.005) or intraventricular hemorrhage (Soy LE 27% vs Mixed LE 15%, P=.03) during their admission. Mixed LE was also associated with significantly lower mean (P=.01), minimum (P=.03), and maximum (P=.04) total bilirubin concentrations across the first 4 weeks after birth. There was no difference in growth velocity or weight, length, and head circumference z-score change. SMOFlipid may represent a favorable alternative to conventional lipid emulsions in neonatal parenteral nutrition regimens; however, long-term effects should be further evaluated.

NIMG-64. IMPACT OF TUMOR LOCATION ON IMAGE-DERIVED VOLUME, PROLIFERATION RATE AND GROWTH VELOCITY IN GLIOBLASTOMA PATIENTS

Abstract INTRODUCTION Glioblastoma (GBM) is the most common malignant primary brain tumor in adults with a median overall survival (OS) of 15months. Despite advancements in treatments, prognosis is dismal and the prognostic significance of tumor location is not entirely understood. METHODOLOGY: In our study, we investigated sex-specific volumetric, tumor growth kinetics, and outcome differences among GBMs in various brain locations. Primary GBM patients with pretreatment magnetic resonance imaging (MRI) data (N=289, 173 males, 116 females) were selected from our brain tumor repository. Tumor abnormality was segmented on T1-weighted post-gadolinium contrast agent (T1Gd) MRIs. We utilized the Harvard-Oxford brain atlases to determine the location of GBMs. RESULTS Overall, our study found smaller tumors in the left hemisphere. This may be expected as left-hemispheric GBM symptoms could present earlier, leading to earlier diagnosis and treatment. However, when the cohort was split by sex, we found this observation significant for females only in the parietal lobe (p &lt; 0.0001). Further, female GBMs demonstrated smaller necrotic volume in the left hemisphere (p = 0.030). Sex-specific differences in incidence were noted in the temporal and occipital lobes (2M:1F). Comparing tumor growth kinetics in different brain locations and hemispheres, females had significantly lower tumor proliferation rates in the left hemisphere (p = 0.009) and lower tumor proliferation rates in the left frontal lobe (p = 0.031). Controlling for treatment, patients with frontal lobe tumors had significantly longer OS compared to those with GBMs in the temporal lobe (p = 0.046, 312 days). Differences in growth velocities were noted between frontal and parietal lobe with frontal GBMs having lower velocities in comparison to parietal lobe GBMs. CONCLUSION Together, our results demonstrate that tumor growth and proliferation rates may vary based on location and sex. Additional research is needed to further explore the clinical significance of tumor location.

Growth patterns of survivors of retinoblastoma treated with ophthalmic artery chemosurgery.

Although studies from pediatric cancers (largely acute lymphoblastic leukemia) have shown that patients undergoing systemic chemotherapy may experience decreased growth velocity during the treatment phase, no such data exist for retinoblastoma patients treated with systemic chemotherapy or ophthalmic artery chemosurgery (OAC). The purpose of this study is to report growth patterns of our retinoblastoma (Rb) population who were treated with OAC in a retrospective, single center (Memorial Sloan Kettering Cancer Center) review of 341 patients treated between 2006 and 2016. Children who only received OAC were classified as naive; those who were treated initially with systemic chemotherapy and subsequently presented to our center for OAC were termed secondary; and a small group of patients who received single-agent systemic chemotherapy prior to OAC were labeled bridge. For all patients, height and weight were recorded at monthly intervals during OAC (short-term) and then annually during a follow-up period (long-term) up to 3 years after treatment. Excluded from this study were children who received external radiation therapy and those with genetic syndromes, which are independently associated with growth derangements. During OAC, there was no significant difference in growth velocity between the naïve and secondary groups. In either group, number of treatments also did not affect growth rate. Three years after the end of OAC, naïve patients were in the 68th percentile by height (95% CI 61.30, 74.63) compared to secondary patients in the 61st percentile (95% CI 51.1, 71.47). Both groups were in the same weight percentiles during the first two years of follow-up but at the three-year follow-up period, naïve patients were in the 63rd percentile (95% CI 57.4, 69.4) and secondary patients were in the 60th percentile (95% CI 50.4, 69.7). OAC for retinoblastoma does not appear to impact short-term growth velocity, weight gain during the treatment period or after three years.

Tumour growth rate of follicular thyroid carcinoma is not different from that of follicular adenoma.

Distinguishing malignancy from benign thyroid nodule has always been challenging, especially in follicular lesions. Thyroid nodules with small size and indeterminate cytology do not lead to immediate surgery. We tried to evaluate whether tumour size and tumour growth rate can distinguish follicular thyroid carcinoma (FTC) from follicular adenoma (FA). This retrospective study included patients with pathologically proven FTCs (n=50) and FAs (n=110) who underwent preoperative serial neck ultrasonography (US) at least 3 times: it comprises 30% of all follicular tumours (32% FAs and 25% FTCs). The growth rates of follicular tumours on serial US were measured using at least 3 consecutive examinations during a median follow-up of 4.1years (range, 0.7-13.3years) by experienced radiologists. The FA and FTC groups showed no significant difference in clinicopathological characteristics, including age, proportion of large nodules (>4cm) and preoperative cytology. The maximum diameter of thyroid nodule was gradually increased in both groups with statistical significance (P<.001 and P<.001, respectively). No significant differences in change of maximum diameter of thyroid nodule (P=.132) and tumour volume (P=.208) were found between the FA and FTC groups during the follow-up. The median time to a significant tumour growth from baseline was not different between the FA and FTC groups (1.4years and 1.7years, respectively, P=.556). When we divided the patients into four groups (rapid, moderate, slow and no growth) according to the growth velocity of the thyroid tumours, no significant difference in growth velocity was found among the groups. The tumour size and growth rate of the thyroid nodule itself could not predict malignancy. Diagnostic approaches that use molecular markers would be more important than clinical features for the decision of diagnostic surgery for patients with follicular tumours.

Infant feeding practice on growth velocity in 4-6 month-olds

Background In developing countries, 5-10% of infants suffer from failure to thrive. Adequate feeding is the most crucial factor for optimal growth in early life.Objective To assess the differences in growth velocity at 4 to 6 months of age, based on the infant feeding practices.Methods This cross-sectional study involving 4 to 6 month-old babies from 6 public health centres in Yogyakarta was performed from August to November 2016. Data on body weight, and growth velocity as they related to weight at birth were collected. Subjects were divided into groups according to their feeding practices.Results Of 173 subjects, 130 (75%) infants were exclusively breastfed, 19 infants (11%) were given breast milk and formula, 14 (8%) infants were given breast milk and complementary food (8%), and 10 (6%) infants were given formula and complementary food. The mean growth velocity z-scores by group were as follows: exclusively breastfed 0.04 (SD 1.15) (95%CI -0.16 to 0.24), breast milk and formula -0.61 (SD 0.84) (95%CI -1.01 to -0.21), breast milk and complementary food -0.69 (SD 1.14) (95%CI -1.35 to -0.04), formula and complementary food 0.23 (SD 1.50) (95%CI: -0.84 to 1.31). The mean difference in growth velocity between the exclusively breastfed vs. breast milk and formula groups was 0.65 (SD 0.28) (95%CI: 0.10 to 1.20; P=0.02); vs. breast milk and complementary food was 0.73 (SD 0.32) (95%CI: 0.10 to 1.37; P=0.02); and vs. formula and complementary food was -0.19 (SD 0.37) (95%CI: -0.93 to 0.55; P=0.61).Conclusion Exclusively breastfed have the most optimal growth velocity compared to infants who experience other feeding practices.

Infant feeding practice on growth velocity in 4-6 month-olds

Background In developing countries, 5-10% of infants suffer from failure to thrive. Adequate feeding is the most crucial factor for optimal growth in early life.Objective To assess the differences in growth velocity at 4 to 6 months of age, based on the infant feeding practices.Methods This cross-sectional study involving 4 to 6 month-old babies from 6 public health centres in Yogyakarta was performed from August to November 2016. Data on body weight, and growth velocity as they related to weight at birth were collected. Subjects were divided into groups according to their feeding practices.Results Of 173 subjects, 130 (75%) infants were exclusively breastfed, 19 infants (11%) were given breast milk and formula, 14 (8%) infants were given breast milk and complementary food (8%), and 10 (6%) infants were given formula and complementary food. The mean growth velocity z-scores by group were as follows: exclusively breastfed 0.04 (SD 1.15) (95%CI -0.16 to 0.24), breast milk and formula -0.61 (SD 0.84) (95%CI -1.01 to -0.21), breast milk and complementary food -0.69 (SD 1.14) (95%CI -1.35 to -0.04), formula and complementary food 0.23 (SD 1.50) (95%CI: -0.84 to 1.31). The mean difference in growth velocity between the exclusively breastfed vs. breast milk and formula groups was 0.65 (SD 0.28) (95%CI: 0.10 to 1.20; P=0.02); vs. breast milk and complementary food was 0.73 (SD 0.32) (95%CI: 0.10 to 1.37; P=0.02); and vs. formula and complementary food was -0.19 (SD 0.37) (95%CI: -0.93 to 0.55; P=0.61).Conclusion Exclusively breastfed have the most optimal growth velocity compared to infants who experience other feeding practices.

Solidification behavior of Co-Sn eutectic alloy with Nb addition

(Co76Sn24)100-xNbx (x = 0, 0.5, 0.8, 1.0) eutectic alloy melts were solidified at small undercooling for investigating the effect of Nb addition on microstructural development. With increasing Nb content, the solidification interface transits from eutectic seaweed (x = 0) to eutectic dendrite (x = 0.5) as a response to the change in the anisotropy of interfacial energy. Coupled eutectic growth can no longer be maintained within the main stems at x = 0.8 because the enrichment of Nb in the liquid ahead of the interface causes a significant difference in growth velocity between the α-Co and β-Co3Sn2 phases and, as such, Co3Sn2 doublons form. For x = 1.0, the difference in growth kinetics between the two eutectic phases is so large that divorced eutectic growth takes place on a large scale. Letting the undercooling prior to solidification increase, the eutectic interface morphology of (Co76Sn24)99.5Nb0.5 eutectic alloys returns from dendritic pattern back to factual seaweed pattern at more than 38 K undercooling and then transits to compact seaweed pattern at more than 181 K undercooling. The eutectic growth velocity slightly increases at low and intermediate undercooling but obviously decreases at large undercooling due with Nb addition.

Relaciones funcionales entre la temperatura del agua de mar y el coeficiente de Brody en cultivos suspendidos de Argopecten purpuratus

Experimentos naturales muestran evidencia que a temperaturas mas altas el crecimiento de Argopecten purpuratus se ve beneficiado. Asi, en condiciones de eventos de El Nino la velocidad de crecimiento se puede hasta duplicar al ser comparada con periodos de su ausencia. Sin embargo, estudios recientes mostraron que aunque las temperaturas promedios de cultivo en Peru (Playa El Carbon) y en Chile (Bahia de Tongoy) pudieran mostrar valores similares, se evidenciaron diferencias en la velocidad de crecimiento. Para explicar esta situacion se relaciono la velocidad de crecimiento mediante regresiones lineales, determinada con el coeficiente de Brody ( k ) de la ecuacion de von Bertalanffy y la temperatura a 10 m de profundidad, utilizandose las unidades termicas acumuladas (UTA) en distintas escalas de tiempo. Los resultados indicaron alta correlacion entre las UTA y k al primer (R 2 = 0,69) y segundo mes de edad (R 2 = 0,80). Los resultados pueden ser utilizados para evaluar el comportamiento futuro de cohortes de ostion del norte o predecir el crecimiento futuro de A. purpuratus en modelos de simulacion bioeconomicos si se dispone de pronosticos oceanograficos de corto, mediano o largo plazo de las condiciones de temperatura en la zona de estudio.

Potential effects of valproate and oxcarbazepine on growth velocity and bone metabolism in epileptic children- a medical center experience.

BackgroundChildren with longstanding use of antiepileptic drugs (AEDs) are susceptible to developing low bone mineral density and an increased fracture risk. However, the literature regarding the effects of AEDs on growth in epileptic children is limited. The aim of this study was to investigate the potential effects of valproate (VPA) and/or oxcarbazepine (OXC) therapy on growth velocity and bone metabolism.MethodsSeventy-three ambulatory children (40 boys and 33 girls) with epilepsy, aged between 1 and 18 years (mean age 9.8 ± 4.1 years), were evaluated for growth velocity before and for 1 year after VPA and/or OXC treatment. The bone resorption marker serum tartrate-resistant acid phosphatase 5b (TRAcP5b) and the bone formation marker serum bone-specific alkaline phosphatase (BAP) were measured post-AEDs therapy for 1 year.ResultsThe difference in growth velocity (ΔHt) and body weight change (ΔWt) between pre- and post-AEDs treatment were -1.0 ± 2.8 cm/year (P < 0.05) and 0.1 ± 3.9 kg/year (P = 0.84), respectively. The study population had serum TRAcP5b-SDS of -1.6 ± 1.2 and BAP-SDS of 1.7 ± 3.7 compared with sex- and age-matched healthy children. Significant correlation between serum TRAcP 5b and BAP activities was noted (r = 0.60, p < 0.001). There was a positive correlation between growth velocity and serum TRAcP 5b activity after AED treatment (r = 0.42, p < 0.01). No correlation was found between ΔHt, ΔWt, serum TRAcP 5b, BAP activity and types of AEDs.ConclusionGrowth velocity was significantly decreased in epileptic children after 1 year of VPA and/or OXC treatment. The effect of VPA and/or OXC therapy on dysregulation of bone metabolism might play a crucial role in physical growth.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0597-7) contains supplementary material, which is available to authorized users.

Impact of Inhaled Corticosteroids on Growth in Children with Asthma: Systematic Review and Meta-Analysis.

BackgroundLong-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth.MethodsWe initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic.ResultsWe found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65).ConclusionUse of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users.

Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth.

Background Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians. Objectives To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma. Search methods We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014. Selection criteria Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma. Data collection and analysis Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Main results Among 22 eligible trials, 17 pairs of groups comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X2 = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, body mass index and skeletal maturation reported with low quality of evidence due to imprecision. Authors' conclusions In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents’ and physicians’ concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth.

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Recommended IGF-I Dosage Causes Greater Fat Accumulation and Osseous Maturation Than Lower Dosage and May Compromise Long-term Growth Effects

The maximum dose of IGF-I recommended for treatment of GH insensitivity is commonly used. The aim was to test the hypothesis that a lower dose is as effective as a high dose of IGF-I in growth promotion and has fewer deleterious effects. Subjects were treated for 3 years with regular examinations including bone age and dual energy x-ray absorptiometry and for 1 year with abdominal ultrasound studies at a clinical research institute in Quito, Ecuador. The study included 21 subjects ages 3.2-15.9 years with GH insensitivity due to the same splice site mutation on the GH receptor gene. Subjects were allocated to receive 120 (n = 14) or 80 (n = 7) μg/kg IGF-I twice daily. Height velocity, osseous maturation, height SD scores (SDS), body composition, abdominal organ growth, and side effects were assessed. There were no differences in growth velocity or height SDS increment by dosage, and the SDS increase was greater than in other reported series. Osseous maturation over 3 years with the high dose was nearly twice as rapid as with the lower dose (P < .001) and correlated with an increase in percentage body fat (r = .64; P < .001) and with adrenal size increase over 1 year (r = .32; P = .03). The ratio of bone age to height age was lower in the high-dose group after 3 years of treatment (P = .007). The commonly used IGF-I dosage of 120 μg/kg twice a day is excessive in comparison to a dose of 80 μg/kg twice a day, disproportionately accelerating osseous maturation, probably from the combined effects of obesity and inappropriate adrenal growth, thus likely compromising adult height potential. Moreover, the lower dose decreases direct treatment cost by one-third.