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The increased availability of recombinant human GH (rhGH), albeit at a relatively high cost, has increased a demand for treatment of children and adolescents of normal height to increase their adult stature. There are no scientific reports on the efficacy and safety of rhGH therapy in this condition; therefore, the authors comment on the possible causes and consequences based on their personal opinion and experience. As in gigantism, when GH action and end-organ are normal, enough GH is expected to result in increased growth velocity. Short-term adverse effects related to rhGH therapy for approved indications of short stature in children have been very rare. Data on long-term adverse effects are still scarce. A small increase in height might be statistically significant but not functionally or socially relevant. Considering that an increase in height represents more a desire than a need, physicians should emphasize the normality and qualities of these children, discuss with families the alternatives, such as counseling, and refrain from supporting the concept that taller is better., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Context: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS)., Objective: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature., Design: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up., Methods: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues., Results: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219)., Conclusions: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined., (© 2024. The Author(s).)

Hemochromatosis (HC) is characterized by the progressive accumulation of iron in the body, resulting in organ damage. Endocrine complications are particularly common, especially when the condition manifests in childhood or adolescence, when HC can adversely affect linear growth or pubertal development, with significant repercussions on quality of life even into adulthood. Therefore, a timely and accurate diagnosis of these disorders is mandatory, but sometimes complex for hematologists without endocrinological support. This is a narrative review focused on puberty and growth disorders during infancy and adolescence aiming to offer guidance for diagnosis, treatment, and proper follow-up. Additionally, it aims to highlight gaps in the existing literature and emphasizes the importance of collaboration among specialists, which is essential in the era of precision medicine., (© 2024 Wiley Periodicals LLC.)

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., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Lactiplantibacillus plantarum promotes growth in undernourished mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain Lp WJL ) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that Lp WJL 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 Lp WJL , 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 Lp WJL -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.

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., Competing Interests: The author have declared that no competing interests exist.

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 (β [95% CI] - 0.953 [- 1.145, - 0.761], p < 0.001), weight (- 0.999 [- 1.176, - 0.807], p < 0.001) and BMI (β [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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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.

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.

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.

(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.

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., (Copyright © 2021 by the American College of Sports Medicine.)

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.

Besides its effects on longitudinal growth in childhood and its metabolic effects with consequences on body composition and lipid levels, growth hormone (GH) has important roles on maintaining the structure and function of the normal adult heart. GH/insulin like growth factor-I (IGF-I) also interacts with the vascular system and plays a role in the regulation of vascular tone. GH deficiency (GHD) in adulthood is associated with increased fat mass (particularly visceral) and abnormal lipid profile, which may contribute to the excess cardiovascular mortality observed in patients with panhypopituitarism. Treatment with GH improved body composition (by increasing lean mass and decreasing fat mass) and improved lipid profile. It also has beneficial effects on vascular walls. The improvement in cardiovascular morbidity and mortality induced by GH is less clear as data are scarce and obtained on small populations. The importance of alteration in cardiac morphology and function observed in GHD is debated, particularly when cardiac magnetic resonance is used rather than echocardiography. The effects of treatment with GH on heart function and morphology are modest when studied by echocardiography., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Qianqian Zhao et al.)

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 β-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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Individuals with postnatal growth retardation (PGR) are prone to developing chronic diseases. Abnormal development in small intestine is casually implicated in impaired growth. However, the exact mechanism is still implausible. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyze developmental changes in intestinal mucosal barrier function. Our data demonstrated that PGR piglets exhibited impaired jejunal and ileal epithelial villous morphology and permeability, accompanied by decreased cell proliferation ability and increased apoptosis rate. In addition, the expression of tight junction proteins (ZO-1, claudin 1, and occludin) and E-cadherin was markedly inhibited by PGR. The expression of P-glycoprotein was significantly reduced in PGR piglets, as well as decreased activity of lysozyme. Moreover, the mRNA abundance and content of inflammatory cytokines were significantly increased in the intestinal mucosa and plasma of PGR piglets, respectively. PGR also contributed to lower level of sIgA, and higher level of CD68-positive rate, β-defensins, and protein expression involved p38 MAPK/NF-κB pathway. Furthermore, PGR altered the intestinal microbial community such as decreased genus Alloprevotella and Oscillospira abundances, and led to lower microbial-derived butyrate production, which may be potential targets for treatment. Collectively, our findings indicated that the intestinal mucosal barrier function of PGR piglets could develop the nutritional intervention strategies in prevention and treatment of the intestinal mucosal barrier dysfunction in piglets and humans., (© 2020 Wiley Periodicals LLC.)

Background: Since 2002, the Department of Pediatrics of Nippon Medical School Chiba Hokusoh Hospital has offered educational activities for children with short stature. We analyzed outcomes of growth hormone (GH) treatment for children with short stature treated at our hospital, particularly outcomes after the growth spurt., Methods: We analyzed data from children aged 0 to 17 years who were treated with recombinant GH during the period from 2000 through 2016 and were followed for at least 2 years after the start of treatment., Results: Among children with short stature, 85 had GH deficiency, 5 had Turner syndrome, 9 were small for gestational age, and 1 had Noonan syndrome. The outcomes of GH treatment was similar to those previously reported in Japan. Children with GH deficiency who started GH treatment before the growth spurt exhibited marked height catch-up until the second year, but the effect decreased after 3 years. The effect of treatment for GH deficiency that was started after the growth spurt continued for 4 to 5 years after the start of treatment., Conclusions: Improvement in height standard deviation score was similar when treatment was started before and after the growth spurt.

Associations between different forms of malnutrition and environmental conditions, including water, sanitation and hygiene (WASH), may contribute towards persistently poor child health, growth and cognitive development. Experiencing poor nutrition in utero or during early childhood is furthermore associated with chronic diseases later in life. The primary responsibility for provision of water and sanitation, as a basic service and human right, lies with the State; however, a number of stakeholders are involved. The situation is most critical in sub-Saharan Africa (SSA), where, in 2015, 311 million people lacked a safe water source, and >70% of SSA populations were living without adequate sanitation. The aim of this paper was to conduct a systematic review to investigate the state of literature concerned with WASH and its association with nutritional status, and governance in children from birth to 5 years of age in SSA. Articles were sourced from PubMed Central, Science Direct and ProQuest Social Science databases published between 1990 and 2017. The PRISMA Statement was utilised and this systematic review is registered with PROSPERO (CRD42017071700). The search terms returned 15,351 articles for screening, with 46 articles included. This is indicative of a limited body of knowledge; however, the number of publications on this topic has been increasing, suggesting burgeoning field of interest. Targeted research on the governance of WASH through the identification of the various role players and stakeholders at various levels, while understanding the policy environment in relation to particular health-related outcomes is imperative to address the burden of child undernutrition.

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.

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., (© 2021 S. Karger AG, Basel.)

Context: Growth retardation is an established complication of anorexia nervosa (AN); however, findings concerning the adult height of AN patients are inconsistent., Objective: The objective of this work was to assess linear growth and adult height in female adolescents with AN., Design and Setting: A prospective observational study was conducted in a tertiary university hospital., Participants: Participants included all 255 female adolescent AN patients hospitalized in the pediatric psychosomatic department between January 1, 2000 and May 31, 2015., Interventions: Height and weight were assessed at admission and during hospitalization. Patients were subsequently invited for measurement of adult height. Additional data collected included premorbid height data, menstrual history, skeletal age, pertinent laboratory studies, and parental heights., Main Outcome Measure: The main outcome measure of this study was adult height., Results: Mean age at admission was 15.4 ± 1.75 years, mean body mass index (BMI) was 15.7 ± 1.8 kg/m2 (BMI SDS = -2.3 ± 1.45 kg/m2). Premorbid height SD scores (SDS) were not significantly different from those expected in normal adolescents (0.005 ± 0.96). However, height SDS at admission (-0.36 ± 0.99), discharge (-0.34 ± 0.96), and at adult height (-0.29 ± 0.95), were significantly (P < .001) lower than expected. Furthermore, adult height was significantly (P = .006) shorter compared to the midparental target height. Stepwise forward linear regression analysis identified age (r = 0.32, P = .002) and bone age (r = -0.29, P = .006) on admission, linear growth during hospitalization (r = 0.47, P < .001), and change in luteinizing hormone during hospitalization (r = -0.265, P = .021) as independent predictors of improvement in height SDS from the time of admission to adult height., Conclusions: Whereas the premorbid height of female adolescent AN patients is normal, linear growth retardation is a prominent feature of their illness. Weight restoration is associated with catch-up growth, but complete catch-up is often not achieved., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders characterized by abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. MPS patients frequently exhibit failures of endochondral ossification during postnatal growth leading to skeletal deformity and short stature. In this review, we outline the current understanding of the cellular and molecular mechanisms underlying failures of endochondral ossification in MPS and discuss associated treatment challenges and opportunities., Recent Findings: Studies in MPS patients and animal models have demonstrated that skeletal cells and tissues exhibit significantly elevated GAG storage from early in postnatal life and that this is associated with impaired cartilage-to-bone conversion in primary and secondary ossification centers, and growth plate dysfunction. Recent studies have begun to elucidate the underlying cellular and molecular mechanisms, including impaired chondrocyte proliferation and hypertrophy, diminished growth factor signaling, disrupted cell cycle progression, impaired autophagy, and increased cell stress and apoptosis. Current treatments such as hematopoietic stem cell transplantation and enzyme replacement therapy fail to normalize endochondral ossification in MPS. Emerging treatments including gene therapy and small molecule-based approaches hold significant promise in this regard. Failures of endochondral ossification contribute to skeletal deformity and short stature in MPS patients, increasing mortality and reducing quality of life. Early intervention is crucial for effective treatment, and there is a critical need for new approaches that normalize endochondral ossification by directly targeting affected cells and signaling pathways.

We use a multivariate multilevel model to study the links between physical fitness (PF) and gross motor coordination (GMC) and investigate the influence of predictors affecting their levels across age. We sampled 7918 Peruvians, aged 6-15 years, from sea-level, Amazon region and high-altitude. Composite markers of GMC and PF were derived (GMC z and PF z , respectively). BMI, biological maturation, and stunting were assessed. School characteristics were obtained via an objective audit. School contexts explained 35% of the associations between PF z and GMC z , whereas children's characteristics explained 65% of the total variation. On average, with increasing age, there was a greater increase in GMC z (β = 0.79 ± 0.04, P < .001) than in PF z (β = 0.15 ± 0.03, P < .001); boys outperformed girls (PF z , β = 3.25 ± 0.08, P < .001; GMC z , β = 1.58 ± 0.09, P < .001); those with lower BMI and ahead in their maturation had higher PF z (β = -0.13 ± 0.01, P < .001; β = 1.09 ± 0.05, P < .001, respectively) and GMC z (β = -0.18 ± 0.01, P < .001; β = 0.39 ± 0.06, P < .001, respectively) levels. Stunting was negatively related to PF z (β = -0.30 ± 0.07; P < .001) and GMC z (β = -0.30 ± 0.08, P < .001) and high-altitude Peruvians had significantly lower GMC z (β = -0.93 ± 0.33, P < .001), and those living in the Amazon region had significantly higher PF z (β = 1.21 ± 0.58, P < .001) compared to those living at sea level. A higher number of students was negatively related to PF z (β = -0.016 ± 0.006, P < .001) and positively with GMC z (β = 0.005 ± 0.003, P < .001); the duration of physical education classes was positively associated with PF z (β = 0.70 ± 0.32, P < .001) and GMC z (β = 0.46 ± 0.15, P < .001); and the existence of policies for physical activity was only negatively associated with GMC z (β = -1.17 ± 0.34, P < .001). In conclusion, PF z and GMC z were positively correlated and child- and school-level traits predicted their levels., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

In this study, we examine the concepts of spatial dependence and spatial heterogeneity in the effect of macro-level and micro-level factors on stunting among children aged under five in Uganda. We conducted a cross-sectional analysis of 3624 Ugandan children aged under five, using data from the 2016 Ugandan Demographic and Health Survey. Multilevel mixed-effect analysis, spatial regression methods and multi-scale geographically weight regression (MGWR) analysis were employed to examine the association between our predictors and stunting as well as to analyse spatial dependence and variability in the association. Approximately 28% of children were stunted. In the multilevel analysis, the effect of drought, diurnal temperature and livestock per km 2 on stunting was modified by child, parent and household factors. Likewise, the contextual factors had a modifiable effect on the association between child's sex, mother's education and stunting. The results of the spatial regression models indicate a significant spatial error dependence in the residuals. The MGWR suggests rainfall and diurnal temperature had spatial varying associations with stunting. The spatial heterogeneity of rainfall and diurnal temperature as predictors of stunting suggest some areas in Uganda might be more sensitive to variability in these climatic conditions in relation to stunting than others.

Golgi matrix protein 130 (GM130), encoded by GOLGA2, is the classical marker of the Golgi apparatus. It plays important roles in various mitotic events, such as interacting with importin-alpha and liberating spindle assembly factor TPX2 to regulate mitotic spindle formation. A previous study showed that in vitro knockdown of GM130 could regulate the meiotic spindle pole assembly. In the current study, we found that knockout (KO) mice progressively died, had a small body size and were completely infertile. Furthermore, we constructed an oocyte-specific GM130 knockout mouse model (GM130-ooKO) driven by Gdf9-Cre. Through breeding assays, we found that the GM130-ooKO mice showed similar fecundity as control mice. During superovulation assays, the KO and GM130-ooKO mice had comparable numbers of ovulated eggs, oocyte maturation rates and normal polar bodies, similar to the control groups. Thus, this study indicated that deletion of GM130 might have a limited impact on the maturation and morphology of oocytes. This might due to more than one golgin sharing the same function, with others compensating for the loss of GM130., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Baraitser-Winter Cerebro-fronto-facial syndrome (BWCFF, OMIM #243310, #614583) is caused by a heterozygous gain-of-function mutation of ACTB and ACTG1 that encodes actin. The syndrome is characterized by striking facial features, structural brain abnormalities, ocular coloboma, hearing loss, cardiac defects, intellectual disabilities, short stature, and developmental delay. We report a two-year-old girl who had distinctive facial features, including hypertelorism, arched eyebrows, bilateral ptosis, short broad nose with a flat nasal tip, long philtrum, retrognathia, low-set ears, and a thin upper lip. In addition, she also exhibited short stature, pectus excavatum, developmental delay, brain malformation, and hearing loss. Targeted gene panel sequencing identified a de novo heterozygous missense variant c.826G>A (p.Glu276Lys) in ACTB This is the first Korean case of BWCFF with a novel mutation in ACTB ., (© 2020 by the Association of Clinical Scientists, Inc.)

Aim: To describe the trajectory of clinical signs in children who developed human immunodeficiency virus encephalopathy (HIVE) after starting early antiretroviral therapy (ART)., Method: This was a retrospective case-cohort description of HIVE among Cape Town participants from the Children with HIV Early AntiRetroviral treatment (CHER) trial. Criteria for HIVE diagnosis were at least two of: (1) acquired central motor deficit, (2) impaired brain growth, and (3) failure to attain or loss of developmental milestones in the absence of an alternative aetiology., Results: Of 133 surviving participants who initiated ART at a median age of 9 weeks and who were followed until a median age of 6 years, 20 (12%) developed HIVE at a median age 31 months (interquartile range 19-37). In these, the first neurological deterioration was noticed at a median age of 19 months, when 16 were on ART and nine had undetectable HIV viral load for a median of 12 months. Signs of upper motor neurons were present in 18, of whom 12 resolved and four had persistent spastic diplegia; 19 had motor delay, of whom 14 resolved; 12 had language delay, of whom 11 resolved; and 16 had impaired brain growth, of whom only five recovered. For the 16 participants already on ART at HIVE diagnosis, regimens were not altered in response to diagnosis., Interpretation: HIVE may occur despite early ART initiation and virological suppression and then resolve on unchanged ART, most likely as intrathecal inflammation subsides., What This Paper Adds: Despite suppressive antiretroviral therapy, children can develop human immunodeficiency virus encephalopathy, The most common manifestations are motor deficits and impaired brain growth. Most experience improvement, with many resolving without additional intervention., (© 2020 Mac Keith Press.)

While weight gain is common following migration to a new country and Mexican Americans have a disparate prevalence of overweight and obesity. In particular, Mexican American women have one of the world's highest rates of Metabolic Syndrome (MetS), characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia, all of which increase the risk for atherosclerotic cardiovascular disease (CVD). Although the etiology of this dilemma is not well understood, using the framework of allostatic load (AL), we posit that exposure to multiple physiologic, psychosocial and environmental stressors over the course of the lifespan may contribute to an increased risk of MetS among indigenous Mexican immigrant women. Two such frequently overlooked stressors are: 1) a history of childhood growth stunting (CGS) and 2) dietary changes post migration that result in decreased diversity of the gut microbiome (dysbiosis). To date, little is known about how migration experiences differentially affect the relationship between CGS and MetS in adulthood. The purpose of this theoretical article is to present a proposed model of how early life stressors (ELS), specifically CGS, may interact with insalubrious aspects of the immigration experience to promote an increased risk for MetS among indigenous Mexican immigrant women. This model may be used in a bi-national effort to guide intervention efforts to decrease CGS in Mexico and to prevent, monitor or delay the components of MetS post migration in the US.

Introduction: Growth impairment has often been described in children who develop coeliac disease (CD). Based on data from the multicentre, longitudinal PreventCD study, we analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD 'cases', 113 infants) versus those who did not develop CD by 6 years (no CD 'controls', 831 infants)., Methods: Weight and length/height were measured using a longitudinal protocol. Raw measurements were standardised, computing z-scores for length/height and weight; a linear mixed model was fitted to the data in order to compare the rate of growth in the two cohorts., Results: Neither cases nor controls had significant growth failure. However, when the mean z-scores for weight and height were analysed, there was a difference between the two groups starting at fourth month of life. When the growth pattern in the first year was analysed longitudinally using mixed models, it emerged that children who develop CD had a significantly lower growth rate in weight z-score (-0.028/month; 95% CI -0.038 to -0.017; p<0.001) and in length/height z-score (-0.018/month; 95% CI -0.031 to -0.005; p=0.008) than those who do not develop CD. When the whole follow-up period was analysed (0-6 years), differences between groups in both weight and length/height z-scores were confirmed., Conclusion: The growth of children at risk of CD rarely fell below 'clinical standards'. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stunting is a worldwide public health problem caused by factors that vary across regions, including in Ethiopia. Limited evidence to prevent stunting makes it difficult to design and prioritize appropriate interventions. Therefore, this study investigated the intervention priorities for the prevention of stunting among children 6-59 months old in Kemissie City Administration, northeastern Ethiopia., Methods: A community-based individual matched case-control study was conducted from January to April 2017 including 107 cases and 214 controls. Controls were selected and matched with cases using the matching variable of child's age. Data were collected by open data kit (ODK) software using a structured questionnaire. Data were analyzed using STATA version 13.0 and WHO (World Health Organization) Anthro 2005. A conditional logistic regression model was used for data analysis. From multivariable conditional logistic regression analysis, determinants of stunting were identified. A statistically significant level was declared by a conditional adjusted odds ratio (cAOR) with 95% confidence interval (CI) and p-value of less than 0.05., Main Findings: The wealth index 52 (48.6%) of the cases and 108 (50.5%) controls were categorized as poor. The mean height-for-age z-score (HAZ) for the cases and controls was -2.79±.67 and -0.55±.92, respectively. One-sixth (16.8%) of the cases and 29 (13.6%) of the controls were given prelacteal feeding. A majority 82 (86.9%) of the cases and 137 (69.1%) of the controls had undernourished mothers/care-givers. Slightly less than one-third 35 (32.7%) of cases and one-fourth 53 (24.8%) of controls were affected by repeated episodes of diarrhea. Mother's body mass index (BMI) (conditional adjusted odds ratio [cAOR]) = 2.64; 95% CI: 1.28, 5.43), giving food priority to father (cAOR = 2.42; 95% CI: 1.23, 4.75), lack of exclusive breastfeeding for at least 6 months (cAOR = 2.44; 95% CI: 1.15, 5.17), no intake of meat by child (cAOR = 2.35; 95% CI: 1.21, 4.58) and child having repeated diarrheal episodes (cAOR = 2.0: 95% CI: 1.07, 3.86) were factors associated with childhood stunting., Conclusion: Maternal nutritional status, food priority, duration of exclusive breastfeeding, no intake of meat and repeated episodes of diarrhea were the main determinants of stunting among children aged 6-59 months. Therefore, intervention measures to avert childhood stunting should include strengthening action on provision of essential nutrition, providing counseling to parents on giving food priority to children, promotion of optimal duration of breastfeeding and preventing diarrheal disease among children 6-59 months old., Competing Interests: The authors have declared that no competing interests exist.

Background: Peru reduced its under-5 child stunting prevalence notably from 31.3% in 2000 to 13.1% in 2016., Objectives: We aimed to study factors and key enablers of child stunting reduction in Peru from 2000-2016., Methods: Demographic and Health Surveys were used to conduct descriptive analyses [height-for-age z scores (HAZ) means and distributions, equity analysis, predicted child growth curves through polynomial regressions] and advanced regression analyses. An ecological (at department level) multilevel regression analysis was conducted to identify the major predictors of stunting decline from 2000 to 2016, and Oaxaca-Blinder decomposition was conducted to identify the relative contribution of each factor to child HAZ change. A systematic literature review, policy and program analysis, and interviews with relevant stakeholders were conducted to understand key drivers of stunting decline in Peru., Results: The distribution of HAZ scores showed a slight rightward shift from 2000 to 2007/2008, and a greater shift from 2007/2008 to 2016. Stunting reduction was higher in the lowest wealth quintile, in rural areas, and among children with the least educated mothers. Decomposing predicted changes showed that the most important factors were increased maternal BMI and maternal height, improved maternal and newborn health care, increased parental education, migration to urban areas, and reduced fertility. Key drivers included the advocacy role of civil society and political leadership around poverty and stunting reduction since the early 2000s. Key enablers included the economic growth and the consolidation of democracy since the early 2000s, and the acknowledgement that stunting reduction needs much more than food supplementation., Conclusions: Peru reduced child stunting owing to improved socioeconomic determinants, sustained implementation of out-of-health-sector and within-health-sector changes, and implementation of health interventions. These efforts were driven through a multisectoral approach, strong civil society advocacy, and keen political leadership. Peru's experience offers useful lessons on how to tackle the problem of stunting under differing scenarios, with the participation of multiple sectors., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Population-based surveys collect crucial data on anthropometric measures to track trends in stunting [height-for-age z score (HAZ) < -2SD] and wasting [weight-for-height z score (WHZ) < -2SD] prevalence among young children globally. However, the quality of the anthropometric data varies between surveys, which may affect population-based estimates of malnutrition., Objectives: We aimed to develop composite indices of anthropometric data quality for use in multisurvey analysis of child health and nutritional status., Methods: We used anthropometric data for children 0-59 mo of age from all publicly available Demographic and Health Surveys (DHS) from 2000 onwards. We derived 6 indicators of anthropometric data quality at the survey level, including 1) date of birth completeness, 2) anthropometric measure completeness, 3) digit preference for height and age, 4) difference in mean HAZ by month of birth, 5) proportion of biologically implausible values, and 6) dispersion of HAZ and WHZ distribution. Principal component factor analysis was used to generate a composite index of anthropometric data quality for HAZ and WHZ separately. Surveys were ranked from the highest (best) to the lowest (worst) index values in anthropometric quality across countries and over time., Results: Of the 145 DHS included, the majority (83 of 145; 57%) were conducted in Sub-Saharan Africa. Surveys were ranked from highest to lowest anthropometric data quality relative to other surveys using the composite index for HAZ. Although slightly higher values in recent DHS suggest potential improvements in anthropometric data quality over time, there continues to be substantial heterogeneity in the quality of anthropometric data across surveys. Results were similar for the WHZ data quality index., Conclusions: A composite index of anthropometric data quality using a parsimonious set of individual indicators can effectively discriminate among surveys with excellent and poor data quality. Such indices can be used to account for variations in anthropometric data quality in multisurvey epidemiologic analyses of child health., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Chronic malnutrition among infants and children continues to represent a global public health concern. The Kyrgyz Republic has achieved rapid declines in stunting over the last 20 y, despite modest increases in gross domestic product per capita., Objective: This study aimed to conduct a systematic, in-depth assessment of national, community, household, and individual drivers of nutrition change and stunting reduction, as well as nutrition-specific and -sensitive policies and programs, in the Kyrgyz Republic., Methods: This mixed methods study employed 4 inquiry methods, including: 1) a systematic scoping literature review; 2) retrospective quantitative data analyses, including linear regression multivariable hierarchical modeling, difference-in-difference analysis, and Oaxaca-Blinder decomposition; 3) qualitative data collection and analysis; and 4) analysis of key nutrition-specific and -sensitive policies and programs., Results: Stunting prevalence has decreased in the Kyrgyz Republic, however, subnational variations and inequities persist. Child growth Victora curves show improvements in height-for-age z-scores (HAZ) for children in the Kyrgyz Republic between 1997 and 2014, indicating increased intrauterine growth and population health improvements. The decomposition analysis explained 88.9% (0.637 SD increase) of the predicted change in HAZ for children under 3 y (1997-2012). Key factors included poverty (61%), maternal nutrition (14%), paternal education (6%), fertility (6%), maternal age (3%), and wealth accumulation (2%). Qualitative analysis revealed poverty reduction, increased migration and remittances, food security, and maternal nutrition as key drivers of stunting decline. Systematic scoping literature review findings supported quantitative and qualitative results, and indicated that land reforms and improved food security represented important factors. Key nutrition-specific and -sensitive policies and programs implemented involved breastfeeding promotion, social protection schemes, and land and health sector reforms., Conclusions: Improvements in stunting were achieved amidst political and economic changes. Multilevel enablers, including poverty reduction, improved food security, and introduction of land and health reforms have contributed to improvements in health, nutrition, and stunting among children in the Kyrgyz Republic., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Progress has been made worldwide in reducing chronic undernutrition and rates of linear growth stunting in children under 5 y of age, although rates still remain high in many regions. Policies, programs, and interventions supporting maternal and child health and nutrition have the potential to improve child growth and development., Objective: This article synthesizes the available global evidence on the drivers of national declines in stunting prevalence and compares the relative effect of major drivers of stunting decline between countries., Methods: We conducted a systematic review of published peer-reviewed and gray literature analyzing the relation between changes in key determinants of child linear growth and contemporaneous changes in linear growth outcomes over time., Results: Among the basic determinants of stunting assessed within regression-decomposition analyses, improvement in asset index score was a consistent and strong driver of improved linear growth outcomes. Increased parental education was also a strong predictor of improved child growth. Of the underlying determinants of stunting, reduced rates of open defecation, improved sanitation infrastructure, and improved access to key maternal health services, including optimal antenatal care and delivery in a health facility or with a skilled birth attendant, all accounted for substantially improved child growth, although the magnitude of variation explained by each differed substantially between countries. At the immediate level, changes in several maternal characteristics predicted modest stunting reductions, including parity, interpregnancy interval, and maternal height., Conclusions: Unique sets of stunting determinants predicted stunting reduction within countries that have reduced stunting. Several common drivers emerge at the basic, underlying, and immediate levels, including improvements in maternal and paternal education, household socioeconomic status, sanitation conditions, maternal health services access, and family planning. Further data collection and in-depth mixed-methods research are required to strengthen recommendations for those countries where the stunting burden remains unacceptably high., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background and Aims: Short stature has been linked with the development of metabolic syndrome (MetS). However, only one study has been conducted in Latin American adults. We aimed to assess the association between short stature and MetS in workers of a private educational institution in Peru. In addition, we evaluated the association between height and surrogate markers of insulin resistance (IR)., Methods: We performed an analytical cross-sectional study. We categorized the height in tertiles and evaluated MetS according to the Latin American Diabetes Association statement. We used the triglycerides and glucose (TyG) index and the triglycerides to HDL-cholesterol (TG/HDL-c) ratio as IR markers. We elaborated crude and adjusted Poisson generalized linear models to evaluate the association between height tertiles and MetS. For the IR markers, we carried out crude and adjusted linear regressions., Results: We analyzed 1080 participants and the overall prevalence of MetS was 16.2%. In the adjusted Poisson generalized linear model, using the high tertile as a reference, we found statistically significant differences in the prevalence of MetS with the low and intermediate tertile (aPR = 2.03; 95%CI: 1.48-2.77 and aPR = 1.41; 95%CI: 1.01-1.99; respectively). In the gender-stratified analysis, we found statistical significance between height and MetS when comparing high and low tertile for both genders. For IR markers, we found an inverse association between the height and TyG index (aβ = -0.14; 95%CI: 0.19 to -0.10) and TG/HDL-c ratio (aβ = -0.62; 95%CI: 0.84 to -0.39). When we stratified by gender, the association for both secondary outcomes and height remained statistically significant in both groups., Conclusions: We found an association between short stature and the prevalence of MetS and IR markers. We need studies with national representative samples to define the threshold of short stature with better sensitivity and specificity for the screening of MetS., Competing Interests: Declaration of competing interest The authors have no potential competing interests., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Introduction: The availability of high-quality studies on the association between sleep-disordered breathing in children and delayed growth associated with the hormonal profile recorded before surgery and at follow-up is limited., Evidence Acquisition: Medline PubMed, Scopus and WebOfScience databases were searched for relevant publications published between January 2008 to January 2020 and a total of 261 potentially eligible studies were identified., Evidence Synthesis: Following review 19 papers were eligible for inclusion: seven reported a significant postsurgical increase in growth regardless of initial weight status, type of surgery, type of study design, and length of follow-up period. The only high-quality study was a randomized controlled trial that found an increased risk of obstructive sleep apnea syndrome relapse in overweight children. Twelve studies reported the significant increase in growth parameters showing that IGF-1, IGFBP-3, and ghrelin may boost growth after surgery., Conclusions: The current systematic review demonstrates a scarcity of high-quality studies on growth delay in children with sleep-disordered breathing. Significant catch-up growth after surgery in the short term and changes in IGF-1, IGFBP-3, ghrelin, and leptin levels has been reported in most published studies.

Objectives Imprinted genes have important roles for normal growth and development. Imprinting disorders (IDs) such as Silver-Russell syndrome and Temple syndrome are rare diseases that typically cause short children born small for gestational age (SGA). However, some patients with short stature (SS) caused by IDs were born non-SGA. To date, the contribution of IDs to idiopathic short stature (ISS) has been poorly investigated. The aim of this study was to clarify the contribution of IDs to ISS. Methods We conducted methylation analysis for 10 differentially methylated regions using pyrosequencing to detect known IDs in 58 patients (31 male and 27 female children, height standard deviation score -4.2 to -2.0) carrying a clinical diagnosis of ISS. Results We identified no patient with IDs among these patients with ISS. Conclusions These results indicate that IDs are rare in patients having ISS, and that imprinted genes affect fetal growth more than postnatal growth. Because patients with IDs born non-SGA usually have clinical features characteristic of each ID, in addition to SS, the patients with ISS as a clinical diagnosis may not be associated with IDs. It is unlikely that cases clinically diagnosed with ISS are caused by IDs leading to growth failure.

Background: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR., Methods: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected., Results: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry., Conclusions: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up., (© 2020 The British Dietetic Association Ltd.)

Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.