Validation of auxological reference values for Japanese children with Noonan syndrome and comparison with growth in children with Turner syndrome.
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ABSTRACT:
SUBMITTER: Isojima T
PROVIDER: S-EPMC5537211 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Single-nucleotide polymorphisms (SNPs) associated with the response to recombinant human growth hormone (r-hGH) have previously been identified in growth hormone deficiency (GHD) and Turner syndrome (TS) children in the PREDICT long-term follow-up (LTFU) study (Nbib699855). Here, we describe the PREDICT validation (VAL) study (Nbib1419249), which aimed to confirm these genetic associations.Children with GHD (n = 293) or TS (n = 132) were recruited retrospectively from 29 sites in nine countries. All children had completed 1 year of r-hGH therapy. 48 SNPs previously identified as associated with first year growth response to r-hGH were genotyped. Regression analysis was used to assess the association between genotype and growth response using clinical/auxological variables as covariates. Further analysis was undertaken using random forest classification.The children were younger, and the growth response was higher in VAL study. Direct genotype analysis did not replicate what was found in the LTFU study. However, using exploratory regression models with covariates, a consistent relationship with growth response in both VAL and LTFU was shown for four genes - SOS1 and INPPL1 in GHD and ESR1 and PTPN1 in TS. The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 ?g/L on GH stimulation test), however, in severe GHD (?4 ?g/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR).The PREDICT validation study supports, in an independent cohort, the association of four of 48 genetic markers with growth response to r-hGH treatment in both pre-pubertal GHD and TS children after controlling for clinical/auxological covariates. However, the contribution of these SNPs in a prediction model of first-year response is not sufficient for routine clinical use.
| S-EPMC5097129 | biostudies-literature
Project description:IntroductionPATRO Children is an international, observational, postmarketing surveillance study for a biosimilar recombinant human growth hormone (rhGH; somatropin, Omnitrope®; Sandoz), approved by the European Medicines Agency in 2006. We report safety and effectiveness data for patients with Turner syndrome (TS).MethodsThe study population included infants, children, and adolescents with TS who received Omnitrope® treatment according to standard clinical practice. Adverse events (AEs) were monitored for safety evaluation, and height velocity (HV), height standard deviation score (HSDS), and HVSDS were calculated to evaluate treatment effectiveness.ResultsAs of August 2019, 348 TS patients were enrolled from 130 centers. At baseline, 314 patients (90.2%) were prepubertal and 284 patients (81.6%) were rhGH treatment naïve. The mean (range) age at baseline was 9.0 (0.7-18.5) years, and mean (SD) treatment duration in the study was 38.5 (26.8) months. Overall, 170 patients (48.9%) reported AEs, which were considered treatment related in 25 patients (7.2%). One treatment-related serious AE was reported (intracranial hypertension). Mean ΔHSDS after 3 years of therapy was +1.17 in treatment-naïve prepubertal patients and +0.1 in pretreated prepubertal patients. In total, 51 patients (31.1%) reached adult height (AH), 35 of whom were rhGH treatment naïve; in these patients, mean (SD) HSDS was -2.97 (1.03) at the start of Omnitrope® treatment, and they achieved a mean (SD) AHSDS of -2.02 (0.9).ConclusionThese data suggest that biosimilar rhGH is well tolerated and effective in TS patients managed in real-life clinical practice. Optimization of rhGH dose may contribute to a higher AH.
| S-EPMC8491505 | biostudies-literature
Project description:BackgroundShort stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS.MethodsThis open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day).ResultsThe change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups.ConclusionsThis study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future.Trial registrationThe study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).
| S-EPMC8662840 | biostudies-literature
Project description:PurposePatients with Turner syndrome (TS) have distinct neurocognitive and psychosocial characteristics. However, few clinical studies have reported neuropsychological findings in Korean patients. This study investigated the neurocognitive and psychosocial profiles of Korean children with TS.MethodsThis retrospective cross-sectional study analyzed 20 pediatric patients (<18 years) with TS at the Department of Pediatric Endocrinology at Yonsei University Severance Children's Hospital in South Korea from January 2016 to March 2019. We selected 20 age- and sex-matched controls from among those who visited the endocrinology clinic and were confirmed to have no clinical abnormalities. All participants underwent several neuropsychological tests.ResultsIn the Korean Wechsler Intelligence Scale for Children-IV test, the Full-Scale Intelligence Quotient of the TS group was within the normal range. The Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index scores were significantly lower in the TS group than in the control group. In contrast, the Verbal Comprehension Index did not differ significantly between the groups. The Comprehensive Attention Test results showed that the TS group displayed borderline visual selective attention. The social quotient score was significantly lower in the TS group than in the control group.ConclusionPediatric patients with TS in Korea displayed distinct neurocognitive and psychosocial characteristics. Patients in the TS group maintained their verbal function, but their attention, visuospatial function, and social competence were low. Our findings will contribute to the development of education programs for patients with TS to improve their neurocognitive and psychosocial functioning.
| S-EPMC10765031 | biostudies-literature
Project description:BackgroundObesity can affect linear growth of children but there is uncertainty regarding the dynamics and potential causes.MethodsIn the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood cohorts (8,629 children, 37,493 measurements), recruited from 1999 to 2018 in Germany, we compared height, growth, and endocrine parameters between normal-weight and children with obesity (0-20 years). Derived from the independent German CrescNet registry (12,703 children) we generated height reference values specific for children with obesity (data collected from 1999 to 2020).FindingsChildren with obesity were significantly taller than normal-weight peers, differing at maximum by 7·6 cm (1·4 height, standard deviation scores or SDS) at age 6-8 years. Already at birth, children with obesity were slightly taller and thereafter had increased growth velocities by up to 1·2 cm/year. This growth acceleration was unrelated to parental height, but was accompanied by increased levels of insulin-like growth factor-1 (IGF-1), insulin and leptin. During puberty, children with obesity showed a catch-down in height SDS. The reduction in pubertal growth velocity by up to 25% coincided with a decrease in levels of IGF-1 (by 17%) and testosterone (by 62%) in boys and estradiol (by 37%) in girls. We confirmed these alterations in growth in the independent CrescNet cohort and furthermore provide height reference values for children with obesity for open access.InterpretationDynamics of linear growth are altered distinctively in different developmental phases in children with obesity. Early emergence before other profound comorbidities implies predisposition, environmental, and/or endocrine factors affecting growth in early life. Height reference values for children with obesity may enhance the precision of clinical health surveillance.FundingGerman Research Foundation, German Diabetes Association, EU, ESF, ERDF, State of Saxony, ESPE, Hexal, Novo Nordisk, Pfizer Pharma.
| S-EPMC8343253 | biostudies-literature
Project description:AimTurner Syndrome (TS) is caused by partial or complete absence of the second sex chromosome in a phenotypic female. TS is associated with recognizable congenital anomalies and chronic health conditions. The principal objective of this study was to evaluate the health-related knowledge and insight of participants.MethodsIn 2015, we founded the UTHealth Turner Syndrome Research Registry for longitudinal follow-up of individuals with TS. Study participants were recruited from UTHealth Houston clinics and the Turner Syndrome Society of the United States. Participants completed a questionnaire about demographics, karyotype, congenital anomalies, health history, frequency of contact with care providers, and knowledge of care providers about TS.ResultsForty percent of registry participants indicated that they did not know their karyotypes. Knowledge of karyotype, which can predict clinical outcomes in TS, markedly varied by self-reported race and ethnicity but not by age. Participants also reported significant gaps in routine medical and gynecologic care.ConclusionWe identified knowledge gaps and health disparities that could benefit from improved provider and patient education.
| S-EPMC10398636 | biostudies-literature
Project description:INTRODUCTION:Cardiopulmonary exercise testing is an essential tool to assess cardiorespiratory fitness (CRF) in children. There is a paucity of adequate pediatric reference values that are independent of body size and pubertal stage. The purpose of this study is to provide Z score equations for several maximal and submaximal CRF parameters derived from a prospectively recruited sample of healthy children. METHODS:In this cross-sectional multicenter study, we prospectively recruited 228 healthy children 12 to 17 yr old in local schools. We performed a symptom-limited cardiopulmonary exercise testing progressive ramp protocol on an electronically braked cycle ergometer. Eighteen CRF parameters were analyzed. We tested several regression models to obtain prediction curves that minimized residual association with age, body size, and pubertal stage. Both the predicted mean and the predicted SD were modeled to account for heteroscedasticity. RESULTS:We identified nonlinear association of CRF parameters with body size and significant heteroscedasticity. To normalize CRF parameters, the use of a single body size variable was not sufficient. We therefore used multivariable models with various combination of height, corrected body mass, and age. Final prediction models yielded adjusted CRF parameters that were independent of age, sex, body mass, height, body mass index, and Tanner stages. CONCLUSIONS:We present Z score equations for several CRF parameters derived from a healthy pediatric population. These reference values provide updated predicted means and range of normality that are independent of sex and body size. Further testing is needed to assess if these reference values increase sensitivity and specificity to identify abnormal cardiorespiratory response in children with chronic diseases.
| S-EPMC6023574 | biostudies-literature
Project description:Individual responses to growth hormone (GH) treatment are variable. Short-term generation of insulin-like growth factor-I (IGF-I) is recognized as a potential marker of sensitivity to GH treatment. This prospective, phase IV study used an integrated genomic analysis to identify markers associated with 1-month change in IGF-I (ΔIGF-I) following initiation of recombinant human (r-h)GH therapy in treatment-naïve children with GH deficiency (GHD) (n=166) or Turner syndrome (TS) (n=147). In both GHD and TS, polymorphisms in the cell-cycle regulator CDK4 were associated with 1-month ΔIGF-I (P<0.05). Baseline gene expression was also correlated with 1-month ΔIGF-I in both GHD and TS (r=0.3; P<0.01). In patients with low IGF-I responses, carriage of specific CDK4 alleles was associated with MAPK and glucocorticoid receptor signaling in GHD, and with p53 and Wnt signaling pathways in TS. Understanding the relationship between genomic markers and early changes in IGF-I may allow development of strategies to rapidly individualize r-hGH dose.
| S-EPMC3959225 | biostudies-literature
Project description:ContextMeasurement of IGF-I is essential for diagnosis and management of patients with disorders affecting the somatotropic axis. However, even when IGF-I kit manufacturers follow recent consensus guidelines, different kits can give very different results for a given sample.ObjectivesWe sought to establish normative data for six IGF-I assay kits based on a large random sample of the French general adult population.Subjects and methodsIn a cross-sectional multicenter cohort study, we measured IGF-I in 911 healthy adults (18-90 years) with six immunoassays (iSYS, LIAISON XL, IMMULITE, IGFI RIACT, Mediagnost ELISA, and Mediagnost RIA). Pairwise concordance between assays was assessed with Bland-Altman plots for both IGF-1 raw data and standard deviation scores (SDS), as well as with the percentage of observed agreement and the weighted Kappa coefficient for categorized IGF-I SDS.ResultsNormative data included the range of values (2.5-97.5 percentiles) given by the six IGF-I assays according to age group and sex. A formula for SDS calculation is provided. Although the lower limits of the reference intervals of the six assays were similar, the upper limits varied markedly. Pairwise concordances were moderate to good (0.38-0.70).ConclusionDespite being obtained in the same healthy population, the reference intervals of the six commercial IGF-1 assay kits showed noteworthy differences. Agreement between methods was moderate to good.
| S-EPMC5054194 | biostudies-literature
Project description:AimsTo generate reference values for two inspiratory muscle endurance (IME) protocols in healthy children and adolescents.Materials and methodsThis is an observational, cross-sectional study, in healthy children and adolescents from 4 to 18 years of age. Weight, height, maximal inspiratory pressure (MIP) and IME were measured using two protocols. A fixed load of 30% of MIP with a 10% increment every 2 minutes was used in the incremental threshold loading protocol. As for the maximal loading protocol, a fixed load of 70% of MIP was used and the time limit (Tlim) achieved until fatigue was measured.ResultsA total of 462 participants were included, 281 corresponding to the incremental loading protocol and 181 to maximal loading. There were moderate and positive correlations between IME and age, MIP, weight and height in the incremental threshold loading. However, the regression model demonstrated that MIP and age were the best variables to predict the IME. Otherwise, weak and positive correlations with age, weight and height were found in the maximal loading. Only age and height influenced endurance in the regression model. The predictive power (r2) of the incremental threshold loading protocol was 0.65, while the maximal loading was 0.15. The reproducibility measured by the intraclass correlation coefficient (ICC) was higher in the incremental loading (0.96) compared to the maximal loading test (0.69).ConclusionIME in healthy children and adolescents can be explained by age, height and MIP. The incremental threshold loading protocol showed more reliable results and should be the model of choice to evaluate IME in the pediatric age group.
| S-EPMC5266249 | biostudies-literature