Gut microbiota in regulation of childhood bone growth.

Childhood stunting and wasting, or decreased linear and ponderal growth associated with undernutrition, continue to be a major global public health challenge. Although many of the current therapeutic and dietary interventions have significantly reduced childhood mortality caused by undernutrition, there remain great inefficacies in improving childhood stunting. Longitudinal bone growth in children is governed by different genetic, nutritional and other environmental factors acting systemically on the endocrine system and locally at the growth plate. Recent studies have shown that this intricate interplay between nutritional and hormonal regulation of the growth plate could involve the gut microbiota, highlighting the importance of a holistic approach in tackling childhood undernutrition. In this review, I focus on the mechanistic insights provided by these recent advances in gut microbiota research and discuss ongoing development of microbiota-based therapeutics in humans, which could be the missing link in solving undernutrition and childhood stunting.

Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

A gut bacterial strain rescues stunted growth.

Lactiplantibacillus plantarum promotes growth in undernourished mice.

Spatiotemporal clustering and correlates of childhood stunting in Ghana: Analysis of the fixed and nonlinear associative effects of socio-demographic and socio-ecological factors.

Childhood stunting remains a major public health issue in many low- and middle-income countries. In Ghana, the progress made is insufficient to reach the targets set by the 2025 World Health Assembly and the 2030 United Nations Sustainable Development Goals. Although studies have examined the socio-demographic determinants of childhood stunting, there has not been any systematic study to examine the spatial associative effects of the socio-demographic and socio-ecological factors at the district level, where health programmes are implemented and monitored. Bayesian geo-additive semiparametric regression technique was used to analyse five conservative rounds of Demographic and Health Surveys in Ghana, with socio-ecological covariates derived from the Demographic and Health Survey Program Geospatial Covariate datasets to examine the temporal trends in childhood stunting, the extent of geospatial clustering at the district level and their associative relationships with socio-demographic and socio-ecological factors. The findings show that childhood stunting in Ghana is not spatially randomly distributed but clustered. Clustering of high childhood stunting was observed amongst districts in the Upper West, Upper East, Northern, North East, Savannah, and Western North regions, whilst clustering of low childhood stunting was observed in districts in the Greater Accra, Volta, Bono and the Eastern regions. Whist socio-demographic factors were predominantly associated with clustering of districts with high childhood stunting, the socio-ecological factors were mainly associated with clustering of districts with low childhood stunting. The socio-ecological factors identified to have a nonlinear associative effect with childhood stunting were Insecticide Treated Net (ITN) coverage, nightlight composite, travel time to a main settlement and population density. The findings suggest that targeted interventions at the district level are essential to reducing childhood stunting in Ghana.

Growth in infants, children and adolescents with unilateral and bilateral cerebral palsy.

To compare growth patterns during infancy, childhood and adolescence in children with unilateral and bilateral cerebral palsy (CP) phenotype and to assess the association with gross motor impairment, dysphagia and gestational age. We retrospectively studied 389 children with CP from a single center population in Munich, Germany. 1536 measurements of height and weight were tabulated and z-scored from 6 to 180 months of age. Generalized linear mixed model were used to examine the association between growth, GMFCS, dysphagia and gestational age by CP phenotype. Children with unilateral CP tend to grow similarly to their typically developed peers. In the main effect model, bilateral CP phenotype was significantly associated with decreased mean z-scores for height (ß [95% CI] - 0.953 [- 1.145, - 0.761], p < 0.001), weight (- 0.999 [- 1.176, - 0.807], p < 0.001) and BMI (ß [95% CI] - 0.437 [- 0.799, - 0.075]), compared with unilateral CP phenotype. This association remained significant in the interaction models. The height-for-age z-scores, weight-for-age decreased z-scores and BMI-for-age z-scores of children with bilateral CP and GMFCS III-V or dysphagia decreased more significantly than those of children with unilateral CP. Preterm birth was not significantly associated with decreased growth in height, weight and BMI. Reduced growth in children with bilateral CP was strongly associated with moderate to severe impairment in gross motor function (GMFCS III-V) and dysphagia.

Long-term growth and final adult height outcome in childhood-onset systemic lupus erythematosus.

BACKGROUND: Growth impairment is the most common complication in patients with childhood-onset systemic lupus erythematosus (cSLE). There are limited data on risk factors affecting growth development in Asian patients with cSLE. This study aimed to determine the predictors of growth impairment in such patients. METHODS: All SLE patients aged < 15 years diagnosed in Ramathibodi Hospital between 2006 and 2016 were enrolled in a retrospective cohort study. Baseline characteristics, including height, weight, clinical manifestations, disease activity score, and medications, were reviewed from medical records from the time at diagnosis to achievement of final adult height (FAH). Age at menarche in girls, adult voice appearance in boys, and parental height were collected by interview. Parent-adjusted FAH (PaFAH) Z-score was calculated as the difference between FAH Z-score for chronological age of the patients and their mid parental height-Z score. The patients were classified into two groups: (1) normal growth (PaFAH Z-score ≥ - 1.5, 2) growth impairment (PaFAH Z-score < - 1.5). Descriptive statistics and logistic regression analysis were used to analyze the data. RESULTS: Of 106 cSLE patients, 19 (18%) were male and 87 (82%) were female. The mean age at study enrollment was 20.6 ± 3.0 years, mean age at diagnosis 12.1 ± 2.3 years, and mean age at achievement of FAH 17.5 ± 1.9 years. Growth impairment was found in 23.6% of patients (52.6% in boys and 17.2% in girls). Predictors of growth impairment were male sex, duration of disease before menarche in girls and adult voice appearance in boys, and cumulative corticosteroid dose (prednisolone equivalent) ≥230 mg/kg received before the late phase of puberty, with odds ratios of 7.07 (95%CI 2.11-23.74), 1.26 (95% CI 1.02-1.56), and 6.99 (95%CI 1.63-30.02), respectively. CONCLUSIONS: One-fourth of cSLE patients developed growth impairment, which mostly affected male patients. Longer duration of disease before the late phase of puberty and corticosteroid dose ≥230 mg/kg received before the late phase of puberty were factors predictive of growth impairment.

Monthly measurement of child lengths between 6 and 27 months of age in Burkina Faso reveals both chronic and episodic growth faltering.

BACKGROUND: Linear growth faltering is determined primarily by attained heights in infancy, but available data consist mainly of cross-sectional heights at each age. OBJECTIVES: This study used longitudinal data to test whether faltering occurs episodically in a few months of very low growth, which could potentially be prevented by timely intervention, or is a chronic condition with slower growth in every month of infancy and early childhood. METHODS: Using anthropometric data collected monthly between August 2014 and December 2016, we investigated individual growth curves of 5039 children ages 6-27 mo in Burkina Faso (108,580 observations). We evaluated growth-curve smoothness by level of attained length at ∼27 mo by analyzing variation in changes in monthly growth rates and using 2-stage regressions: 1) regressing each child's length on their age and extracting R2 to represent curve smoothness, initial length, and average velocity by age; and 2) regressing extracted parameters on individual-level attained length. RESULTS: Short children started smaller and remained on their initial trajectories, continuously growing slower than taller children. Growth between 9 and 11 mo was the most influential on attained length; for each 1-cm/mo increase in growth velocity during this period, attained length increased by 6.71 cm (95% CI: 6.59, 6.83 cm). Furthermore, a 0.01 increase in R2 from individual regression of length on age was associated with a 3.10-cm higher attained length (95% CI: 2.80, 3.41 cm), and having 2 consecutive months of slow growth (<15th centile relative to the sample) was associated with 1.7-cm lower attained length (95% CI: -1.80, -1.59 cm), with larger effects in younger children, suggesting that smoother growth patterns were also associated with higher attained length. CONCLUSIONS: Children who experience extreme growth faltering are likely less resilient to systematic growth-limiting conditions as well as episodic insults to their growth.This trial was registered at clinicaltrials.gov as NCT02071563.

Most Short Children with Cystic Fibrosis Do Not Catch Up by Adulthood.

Poor linear growth is common in children with cystic fibrosis (CF) and predicts pulmonary status and mortality. Growth impairment develops in infancy, prior to pulmonary decline and despite aggressive nutritional measures. We hypothesized that growth restriction during early childhood in CF is associated with reduced adult height. We used the Cystic Fibrosis Foundation (CFF) patient registry to identify CF adults between 2011 and 2015 (ages 18-19 y, n = 3655) and had height for age (HFA) records between ages 2 and 4 y. We found that only 26% CF adults were ≥median HFA and 25% were <10th percentile. Between 2 and 4 years, those with height < 10th percentile had increased odds of being <10th percentile in adulthood compared to children ≥ 10th percentile (OR = 7.7). Of HFA measured between the 10th and 25th percentiles at ages 2-4, 58% were <25th percentile as adults. Only 13% between the 10th and 25th percentile HFA at age 2-4 years were >50th percentile as adults. Maximum height between ages 2 and 4 highly correlated with adult height. These results demonstrate that low early childhood CF height correlates with height in adulthood. Since linear growth correlates with lung growth, identifying both risk factors and interventions for growth failure (nutritional support, confounders of clinical care, and potential endocrine involvement) could lead to improved overall health.

Associations of Growth Impairment and Body Composition among South African School-Aged Children Enrolled in the KaziAfya Project.

(1) Background: Early childhood malnutrition may result in increased fat mass (FM) among school-aged children in low- and middle-income countries (LMICs). We explored whether South African children with shorter stature have greater overall and abdominal FM compared to normal stature children. (2) Methods: Baseline assessments of body composition and weight were determined among school-aged children enrolled in a randomized controlled trial in Port Elizabeth, South Africa, using bioelectrical impedance analysis. Multiple linear regression models tested associations of children's height and degree of stunting with FM, fat free mass (FFM), truncal fat mass (TrFM), and truncal fat free mass (TrFFM) overall and by sex. (3) Results: A total of 1287 children (619 girls, 668 boys) were assessed at baseline. Reduced child height was associated with higher FM and lower FFM and TrFFM, but these associations were reversed with increases in height. Girls classified as mildly or moderately/severely stunted had higher FM and TrFM but lower FFM and TrFFM, while no association was found for boys. (4) Conclusions: Our study suggests that efforts to reduce the non-communicable disease burden in LMICs should target growth-impaired children who may have greater overall FM and greater abdominal FM.

The Double Burden of Malnutrition and Associated Factors among South Asian Adolescents: Findings from the Global School-Based Student Health Survey.

The health and nutrition of the global adolescent population have been under-researched, in spite of its significant size (1.2 billion). This study investigates the prevalence and associated factors of malnutrition (stunting, thinness and overweight) among adolescents living in South Asia. The sample analysed was 24,053 South Asian schooled adolescents aged 12-15 years that participated in the cross-sectional Global School-Based Student Health Survey (GSHS) between 2009 and 2016. The prevalence of stunting, thinness and overweight was calculated using the World Health Organization (WHO) Child Growth Reference 2007. Associations between the three forms of malnutrition and their possible associated factors were assessed with binary logistic regression analysis using bootstrapping as a resampling method. The overall prevalence of stunting in South Asia was 13%, thinness was 10.8% and overweight was 10.8%. In the logistic regression model of the overall pooled sample, the factors associated with adolescent malnutrition were: age, hygiene behaviours, social support, sedentary behaviour, and tobacco use. A substantial proportion of stunting, thinness and overweight was found among school-going South Asian adolescents, indicating that the double burden of malnutrition is present in this population. Future research should seek to further understand the relationship between all forms of malnutrition and its associated factors in the adolescent population.

Twenty-year follow-up of the facial phenotype of Brazilian patients with Sotos syndrome.

Sotos syndrome is characterized by overgrowth starting before birth through childhood with intellectual disability and craniofacial anomalies. The majority of patients are large for gestational age with developmental delay or intellectual disability. The majority of cases are caused by pathogenic variants in NSD1. The most consistent physical features in this disorder are facial dysmorphisms including prominent forehead, downslanted palpebral fissures, prognathism with a pointed chin, and a long and narrow face. We present a follow-up to a cohort of 11 individuals found to harbor heterozygous, pathogenic, or likely pathogenic variants in NSD1. We analyzed the facial dysmorphisms and the condition using retrospective over 20 years. Among these patients, followed in our medical genetics outpatient clinic for variable periods of time, all had a phenotype compatible with the characteristic Sotos syndrome facial features, which evolved with time and became superimposed with natural aging modifications. We present here a long-term follow-up of facial features of Brazilian patients with molecularly confirmed Sotos syndrome. In this largest Brazilian cohort of molecularly confirmed patients with Sotos syndrome to date, we provide a careful description of the facial phenotype, which becomes less pronounced with aging and possibly more difficult to recognize in adults. These results may have broad clinical implications for diagnosis and add to the global clinical delineation of this condition.

Trends in underweight, stunting, and wasting prevalence and inequality among children under three in Indian states, 1993-2016.

Child undernutrition remains high in India with far-reaching consequences for child health and development. Anthropometry reflects undernutrition. We examined the state-level trends in underweight, stunting, and wasting prevalence and inequality by living standards using four rounds of the National Family Health Surveys in 26 states in India, conducted in 1992-1993, 1998-1999, 2005-2006, and 2015-2016. The average annual reduction (AAR) for underweight ranged from 0.04 percentage points (pp) (95% CI - 0.12, 0.20) in Haryana to 1.05 pp (95% CI 0.88, 1.22) in West Bengal for underweight; 0.35 pp (95% CI 0.11, 0.59) in Manipur to 1.47 (95% CI 1.19, 1.75) in Himachal Pradesh for stunting; and - 0.65 pp (95% CI - 0.77, - 0.52) in Haryana to 0.36 pp (95% CI 0.22, 0.51) in Bihar & Jharkhand for wasting. We find that change in the pp difference between children with the poorest and richest household living standards varied by states: statistically significant decline (increase) was observed in 5 (3) states for underweight, 5 (4) states for stunting, and 2 (1) states for wasting. Prevalence of poor anthropometric outcomes as well as disparities by states and living standards remain a problem in India.

Physical Activity Engagement Worsens Health Outcomes and Limits Exercise Capacity in Growth-restricted Mice.

INTRODUCTION: A total of 161 million children a year are growth restricted, leading to a 47% increased risk of chronic disease in adulthood. Physical activity (PA) reduces the risk of mortality from chronic disease. The purpose of the present investigation was to determine the effect of a PA intervention (wheel running) on cardiac and skeletal muscle capacities in gestational (GUN) and postnatal (PUN) growth-restricted mice as compared with nonrestricted controls (CON). METHODS: A low-protein cross-fostering FVB mouse model was used to induce growth restriction during gestation and the first 21 d of postnatal life. Mouse pups were recovered on a healthy diet until mature and provided wheel access for 3 wk. At completion of the PA intervention, mice underwent maximal exercise testing on a treadmill, echocardiography, and skeletal muscle histology. RESULTS: After the PA intervention, CON mice had a 45% improvement in maximal exercise capacity (P = 0.0390) because of cardiac and skeletal muscle adaptations, but GUN and PUN mice did not. Alarmingly, PUN female mice exposed to wheels had 11.45% lower left ventricular volume (P = 0.0540) and 18% lower left ventricle area (P = 0.0585), with blood flow velocities indicative of cardiac fibrosis (GUN had elevated isovolumetric contraction time P = 0.0374; GUN females and PUN males had longer isovolumetric relaxation time P = 0.0703). PUN male mice had mixed skeletal muscle responses with an oxidative shift in the diaphragm (P = 0.0162) but a glycolytic shift in the extensor digitorum longus (P = 0.0647). PUN female mice had a glycolytic shift in the soleus after wheel running. CONCLUSIONS: Unexpectedly, growth-restricted mice were nonresponders to a PA intervention and displayed negative cardiac outcomes.

Adult Height in 299 Patients with Turner Syndrome with or without Growth Hormone Therapy: Results and Literature Review.

CONTEXT: Treatment with growth hormone (GH) is considered effective in improving adult height (AH) in Turner syndrome (TS). However, there are few studies comparing AH between treated patients and a concurrent untreated group. OBJECTIVE: To assess the efficacy of GH treatment in improving AH in TS and to review previous published studies with treated and untreated groups. PARTICIPANTS AND METHODS: We retrospectively analyzed clinical data and AH of a large cohort of GH-treated (n = 168) and untreated (n = 131) patients with TS. Data are shown as median and interquartile range (IQR). We assessed pretreatment variables related with AH and compared our results with 16 studies that also included an untreated group. RESULTS: The GH-treated group was 6.2 cm taller than the untreated group (AH = 149 cm [IQR 144.5-152.5 cm] vs. 142.8 cm [IQR 139-148 cm], p < 0.001) after 4.9 years of GH treatment with a dose of 0.35 mg/kg/week. AH SDS corrected for target height (TH) was 7.2 cm higher in GH-treated patients. AH SDS ≥-2 was more frequent in GH-treated patients (43%) than in untreated patients (16%, p < 0.001). AH SDS was also more frequently within the TH range in the GH-treated group (52%) than in the untreated group (15%, p < 0.001). Height SDS at start of GH therapy and TH SDS were positively correlated with AH (p < 0.001; R2 = 0.375). Considering the current result together with previous similar publications, a mean AH gain of 5.7 cm was observed in GH-treated (n = 696) versus untreated (n = 633) patients. CONCLUSIONS: Our study strengthens the evidence for efficacy of GH therapy in patients with TS from different populations.

A Retrospective Analysis of Patients with Short Stature in Eastern China between 2013 and 2019.

OBJECTIVE: To identify the aetiology of growth and development diseases and assess the long-term effectiveness of recombinant human growth hormone (rhGH) therapy in a real-life clinical setting and provide better guidance in clinical strategy and decision making. METHODS: This retrospective study included 1145 children and adolescents with short stature admitted to the Department of Endocrinology, Affiliated Hospital of Jining Medical University, from January 2013 to December 2019, of whom 484 received rhGH treatment. The related anthropometrics and laboratory examinations were assessed in all participants. RESULTS: A total of 1145 children and adolescents with short stature aged 10.5 ± 3.3 years, including 740 boys and 405 girls, were analysed in this study. The number of children and adolescents with short stature gradually increased per year from 2013 to 2019. The mean pretreatment height standard deviation score (SDS) and insulin-like growth factor-1 SDS were -2.93 ± 1.05 and -1.01 (-1.83--0.16), respectively. The majority of the children (658, 57.47%) were prepubescent. In total, 484 subjects aged 10.6 ± 3.2 years received rhGH and were followed up, and among them, 292 children were treated for more than one year. As the treatment time increased, the children's height SDS gradually increased, and most of them attained a height SDS within the normal range. The mean height SDS in children who were treated for more than one year was -3.0 ± 1.0 at baseline and gradually increased to -0.8 ± 0.3 by year 6. The results were consistent across subgroups of different aetiologies of short stature. CONCLUSIONS: Increasing attention has been given to the height of children during the period of 2013-2019 in eastern China. The present findings indicate that children with short stature need to be referred to a specialist centre to diagnose the cause of growth failure and that short children receiving rhGH therapy show a significant increase in height over time.

Impact of short stature on quality of life: A systematic literature review.

OBJECTIVE: We sought to obtain a better understanding of the burden of short stature using a systematic literature review. METHODS: Studies of the burden of short stature, of any cause in adults and children, were searched using Embase, MEDLINE and Cochrane databases in April 2020, capturing publications from 2008 onwards. Case series and populations with adult-onset growth hormone deficiency (GHD) were excluded. RESULTS: Of 1684 publications identified, 41 studies (33 in children, 8 in adults) were included. All studies assessed human burden. Most study populations in children included short stature due to GHD, idiopathic short stature (ISS) and short stature after being born small for gestational age (SGA). In these populations, four studies showed that quality of life (QoL) in children with short stature was significantly worse than in children with normal stature. A significant association between QoL and short stature was observed in children with chronic kidney disease (CKD) (3 studies), achondroplasia (1 study) and transfusion-dependent ß-thalassaemia (1 study), and in samples with mixed causes of short stature (3 studies). Three studies (one in GHD/ISS/SGA and two in CKD) found no significant association between short stature and QoL, and several studies did not report statistical significance. Approximately half of adult studies showed that QoL was reduced with short stature, and the other half showed no association. Two studies, one in adults with Prader-Willi syndrome and one in children with GHD, suggested a potential association between short stature and poorer cognitive outcomes. Three studies demonstrated an increased caregiver burden in parents of children with short stature. CONCLUSIONS: Evidence suggests that, compared with those with normal stature, children and adults with short stature of any cause may experience poorer QoL. Further research could extend our understanding of the human burden in this field.

Identification of a novel pathogenic variant in CKAP2L and literature review in a child with Filippi syndrome and congenital talipes equinovarus.

Filippi syndrome (MIM #272440), one of the craniodigital syndromes, is a rare genetic entity with autosomal recessive inheritance and characterized by pre- and postnatal growth retardation, microcephaly, distinctive facial appearance, developmental delay/intellectual disability, and variable syndactylies of the fingers and toes. In this report, a further female patient of Filippi syndrome who additionally had a unilateral congenital talipes equinovarus (CTEV), a feature not previously recorded, is described. Genetic testing revealed a novel homozygous frameshift pathogenic variant (c.552_555delCAAA, p.Asn184Lysfs*8) in CKAP2L and thus confirmed the diagnosis of Filippi syndrome. We hope that the newly recognized feature (CTEV) will contribute to expand the clinical spectrum of this extremely rare condition. In view of the paucity of reported cases, the full spectrum of clinical findings of Filippi syndrome necessitates obviously further affected individuals/pedigrees delineation in order to elucidate the etiological and phenotypic aspects of this orphan disease appropriately.

Transgenic mice with an R342X mutation in Phf6 display clinical features of Börjeson-Forssman-Lehmann Syndrome.

The PHF6 mutation c.1024C > T; p.R342X, is a recurrent cause of Börjeson-Forssman-Lehmann Syndrome (BFLS), a neurodevelopmental disorder characterized by moderate-severe intellectual disability, truncal obesity, gynecomastia, hypogonadism, long tapering fingers and large ears (MIM#301900). Here, we generated transgenic mice with the identical substitution (R342X mice) using CRISPR technology. We show that the p.R342X mutation causes a reduction in PHF6 protein levels, in both human and mice, from nonsense-mediated decay and nonsense-associated alternative splicing, respectively. Magnetic resonance imaging studies indicated that R342X mice had a reduced brain volume on a mixed genetic background but developed hydrocephaly and a high incidence of postnatal death on a C57BL/6 background. Cortical development proceeded normally, while hippocampus and hypothalamus relative brain volumes were altered. A hypoplastic anterior pituitary was also observed that likely contributes to the small size of the R342X mice. Behavior testing demonstrated deficits in associative learning, spatial memory and an anxiolytic phenotype. Taken together, the R342X mice represent a good preclinical model of BFLS that will allow further dissection of PHF6 function and disease pathogenesis.

Evaluation of Growth Hormone Results in Different Diagnosis and Trend Over 10 Year of Follow-up: A Single Center Experience

Objective: The aim was to evaluate the results of diagnosis, follow-up and treatment of the patients who recieved growth hormone (GH) treatment for the last 10 years and to determine the differences in the process and results over the years. Methods: Anthropometric, clinical, laboratory data, treatment adherence and side effects were evaluated retrospectively in 767 patients who recieved GH treatment between 2009-2018. Patients were grouped as isolated GH deficiency (IGHD), multiple pituitary hormone deficiency (MPHD), small for gestational age (SGA), and Turner syndrome (TS) depending on diagnosis. Results: GH treatment was started in 689 cases (89.8%) with IGHD, 24 (3.1%) with MPHD, 26 (3.4%) with SGA and 28 (3.7%) with TS. Median age of GH treatment onset was the earliest in SGA (8.4 years) and the latest in the IGHD group (12.0 years). At the time of treatment cessation, height standard deviation score (SDS) in IGHD and MPHD was significantly higher than treatment initiation time, whereas there was no significant difference in TS and SGA. One hundred eighty-nine cases reached the final height. Final heights for girls/boys were: IGHD 154/164.9 cm; MPHD 156.2/163.5 cm; TS 146.7 cm; and SGA 145.7/-cm, respectively. Target height SDS-final height SDS median values were IGHD: 0.1, MPHD: 0.6, SGA: 0.5, TS: 2.4 respectively. The patients' treatment compliance was high (92%) and the incidence of side effects was low (2.7%). Conclusion: In our cohort, GH treatment start age was late and no difference in this was observed in the last 10 years. The improvement in the height SDS was most marked in the IGHD and MPHD groups, the least in the TS and SGA groups.