Growth Disorders Research Articles

The impact of soil-transmitted helminths infection on growth impairment: systematic review and meta analysis

Human helminthiasis, particularly soil-transmitted helminth (STH) infections, is a prevalent health concern in Indonesia, especially among children, often resulting in growth disorders, notably stunting. To examine the link between STH infections and childhood stunting, we conducted a comprehensive review of literature spanning 2012-2023, encompassing 40 selected articles from databases like PubMed, Science Direct, and Google Scholar. Our analysis revealed a substantial association between STH infections and increased stunting risk in children, estimating a 44.407% rise in stunting risk due to STH infection. Stunting, a consequence of chronic malnutrition, profoundly affects a child's physical and cognitive development, with long-lasting repercussions on their future potential and quality of life. This study has significant implications. It underscores the urgent need for robust public health interventions targeting STH infections, especially in high-prevalence areas like Indonesia. Measures such as mass deworming campaigns, improved sanitation and hygiene practices, and health education can significantly alleviate the burden of STH infections and the resulting stunting. Moreover, the research emphasizes the intricate relationship between infectious diseases and malnutrition, highlighting the necessity for a holistic approach to child health. Addressing STH infections necessitates not only medical intervention but also efforts to enhance overall living conditions and nutritional status. Integrating these approaches into a comprehensive public health strategy can yield more effective and sustainable results in the fight against childhood stunting. In conclusion, this study underscores the paramount importance of addressing STH infections in the context of child growth and underscores the urgency of implementing effective public health interventions. This approach can enable children to reach their full physical and cognitive potential, ultimately contributing to the overall well-being and development of societies.

Association Between Adolescent Pregnancy and Stunting Incidence: A Scoping Review

Background: Stunting is a developmental disorder that occurs in children caused by malnutrition, frequent infections, and poor psychosocial simulation. Stunting can be influenced by some factors such as infection, exclusive breastfeeding, early initiation of breastfeeding, and adolescent pregnancy. This study aims to review the association between adolescent pregnancy and stunting incidence.Method: This scoping review used the PRISMA-ScR framework by searching for articles from relevant databases such as Pubmed, EBSCO, and Wiley. The article search obtained ten articles for further analysis. The article was analyzed based on the Joanna Briggs Institute (JBI). The keywords used were Teen Pregnancy* OR Adolescent Pregnancy* OR Teen Pregnancies* AND Nutritional Deficiency* OR Undernutrition* OR Growth Disorder* OR Stunting*. Besides, the researcher added a filter, namely articles published in the last five years (2018-2022), articles that are open access, and original research articles.Results: Based on the results of reviewing the ten articles, it can be concluded that adolescent pregnancy is significantly associated with stunting incidence in adolescents with low education levels and poor economic conditions leading to poor health awareness and nutritional status. Future studies are expected to further evaluate the relationship between adolescent pregnancy and stunting incidence

DESCRIPTIVE STUDY OF LOW BIRTH WEIGHT INFANTS AT SEPASO HEALTH CENTER

Low birth weight (LBW) infants are a serious health issue in Indonesia. LBW is associated with high mortality rates, chronic diseases risks, and growth and developmental disorders in children. This study aims to provide an overview of LBW occurrence at Sepaso Health Center. This research employed a descriptive research design. According to Sumadi (2016), descriptive research aims to provide a description of a situation or event. A case study approach was used in this research design, where information was collected to understand a specific event or problem. The population of this study consisted of individuals with authority regarding the influence of LBW infants at Sepaso Health Center. Purposive sampling technique was utilized for sample selection. Based on the research conducted on 30 mothers with low birth weight (LBW) infants, the findings revealed that 60% of the mothers were at risk due to being below 20 years or above 35 years old, while 40% of the mothers were not at risk with ages between 20-35 years. Parity showed that 30% were nulliparous and 70% were multiparous. Maternal occupation indicated that 40% were employed and 60% were unemployed. Antenatal care (ANC) distribution showed that 40% had frequent ANC visits, while 60% had inadequate ANC visits. Maternal food consumption during pregnancy showed that 27% had good consumption, 67% had sufficient consumption, and 6% had inadequate consumption. These findings can serve as a basis for enhancing attention and care for low birth weight infants at the Sepaso Health Center. It is expected that this study can contribute to the efforts in improving the health of low birth weight infants in the region.

MATERNAL KNOWLEDGE REGARDING THE FIRST 1000 DAYS OF LIFE WITH THE INCIDENCE OF STUNTED CHILDREN UNDER THE AGE OF FIVE IN THE WORKING AREA OF SUKOMULYO COMMUNITY HEALTH CENTER

Background: Stunting is a global and national health problem. The World Health Organization (WHO) determines that if the prevalence of stunting is between 30-39%. Based on the reports of Riskesdas in 2010, it was reported that 35.6% of Indonesian children under five were stunted. Stunting is a condition that describes a linear growth disorder characterized by height that is below normal standards for age and sex that is commonly associated with malnutrition and chronic (non-endocrine) infections. The stunting intervention was focused on 1000 Hari Pertama Kehidupan (HPK) period, which is a golden period of a child and if not utilized appropriately, permanent damage could occur. Objective: To determine the correlation between maternal knowledge levels regarding 1000 HPK and the incidence of stunting in children under five. Methods: This study used an observational analytic method with a cross sectional design. Sampling was done with consecutive sampling technique. In this study, will be examined for body length using a stadiometer. After that, the mother will be interviewed to find out the correlation between mother's knowledge regarding 1000 HPK and the incidence of stunting in toddlers. Then the stunting and normal children will be grouped based on the standardized WHO growth chart. Results: Kendall's tau-b statistical test showed a significant relationship (p = 0.000) with positive moderate strength correlation (τ = 0.442). Conclusion: There is a significant relationship and a moderate strength positive correlation between the mother's level of knowledge regarding 1000 HPK and the incidence of stunting Keywords: Maternal knowledge of 1000 HPK, Stunted, Children under five

ANALYSIS OF POLICY IMPLEMENTATION SYSTEM PROGRAM FOR GIVING FE TABLETS TO ADOLESCENT WOMEN IN SCHOOL AS A PREVENTION EFFORT STUNTING IN TOBA DISTRICT THE YEAR 2023

Stunting is a growth and development disorder in children due to critical malnutrition. Adolescence is a transition from childhood to adulthood which in its growth requires greater nutrition compared to other ages, especially iron. Adolescent health will determine the success of development in presenting a quality generation of the nation in the future. Adolescent girls are prospective mothers who will become pregnant and give birth, so efforts are made to obtain sufficient iron by administering Blood Supplement Tablets (TTD). This research is qualitative research with a phenomenological study design. This study displays a picture of a person's life experience when each individual subjectively feels the experience of a situation. The main informants were the nutrition manager at the health center, the teacher in charge of the UKS, and young female students who consumed iron supplement tablets. Triangulation informants are the Head of the Public Health Sector, the Nutrition Manager for the Health Service, the Promotion Manager for the Public Health Service, and the Head of the Health Center. The sample was determined using the Side Purposive technique, totaling 13 people. Competent human resources to facilitate and speed up the smooth running of the program. Facilities and infrastructure are in good condition and able to support program implementation. Planning, Actuating, and controlling went very well and clearly. The program coverage showed a decrease in the prevalence of stunting from the previous year of 26.92%. The program by giving Fe tablets to young women at schools in Toba Regency has succeeded in reducing the number of stunting cases.

DETERMINANTS OF STUNTING IN SEMARANG CITY

Background : Stunting is not only a problem of physical growth disorders, but also causes children to become sick easily, brain and intelligence development also occurs. So, stunting is a big threat to the quality of human resources in Indonesia. The purpose of writing of this literature review is to collect determinants of Stunting in Semarang.
 Objective : This research uses a literature revies from Google Scholar library sources, which is presented descriptively according to the problem formulation.
 Result : Review from some of articles, found that maternal education level, maternal occupation, child order, birth length, child rearing patterns, exclusive breastfeeding status, family income, housing conditions, nutritional intake, and history of KEK are risk factors determining the incidence of Stunting in the Semarang. 
 Conclusions : Stunting prevention programs must be improved, by screening and monitoring the growth and development of babies and toddlers to prevent Stunting from an early age. Public is also advised to be more diligent in carrying out examinations at health services to monitor children’s growth and development.

The Relationship Between Mothers’ Knowledge On Posyandu Services And Their Frequency Of Visit To Posyandu In Karangrejo Village Purworejo Regency

Integrated Service Post (Posyandu) is among the Community-based Health Efforts (UKBM) managed by and for benefits of the community members assisted by health workers’ technical supports. Posyandu is a strategy implemented by the Indonesian government and assigned by the Ministry of Health to conduct early detection of any growth disorders among toddlers, especially stunting (growth failure). However, in reality, the community hardly use Posyandu services due to mother’s lack of knowledge regarding the services. This study was aimed to investigate the relationship between mothers’ knowledge on Posyandu services and their frequency of visit to Posyandu in Karangrejo village, Purworejo regency. The researcher implemented quantitative approach with observational analytic method and cross-sectional research design. The respondents were mothers with 12-59 months aged children in Karangrejo village. There were 44 participants chosen using total sampling technique. Spearman’s rank statistical test revealed that 20 respondents (45.4%) had good knowledge on Posyandu services and therefore frequently visited Posyandu for their toddlers while 5 of them (11.4%) had little knowledge on the services which explained why they did not pay regular visits to Posyandu. Further, the results showed p-value=0.000 and correlation coefficient 0.698 meaning that the relationship of mothers’ knowledge on Posyandu services and their frequency of visit to Posyandu in Karangrejo village, Purworejo regency was considered to be moderate (C=0.698). It is suggested that mothers with children of 12-59 months age regularly visit Posyandu to ensure the good growth of their children.

Risk Factors of Stunting in Toddlers in The Village of Gunung Batin Udik, Lampung Tengah

Nutritional status in Indonesia, especially in toddlers is still a health problem, including malnutrition and stunting. Stunting is a linear growth disorder caused by chronic malnutrition or recurrent chronic infectious diseases. Risk Factors for chronic nutritional status in toddlers are not the same between regions, so this study aims to determine the risk factors for stunting in children under five in Gunung Batin Udik Village. This type of research was quantitative and the research design used observational analytics with a case-control approach. When this research was conducted on 5-20 November 2021 in Gunung Batin Udik Village, Terusan Nyunyai District, Central Lampung Regency in 2021. The population in this study were all toddlers of age 1-5 years old with a sample size of 120 respondents using simple random technique sampling. Data collection used questionnaires and observations then analyzed with the chi-square test. The results showed several risk factors for stunting events such as exclusive breastfeeding (OR: 2.704), mother's education level (OR: 3.455), mother's knowledge level (OR: 2.444), and family income (OR: 3.541). Whereas the fewer risk factors such as LBW (OR: 1,588), mother's employment status (OR: 2,093), latrine ownership (OR: 1,481), ownership of standard trash bins (OR: 0.576), and standard SPAL (OR: 0.619). Several factors are at risk for the incidence of stunting in infants.

Baby Massage Training in The Covid-19 Pandemi

Disturbances or difficulties will usually interfere with the ideal growth and development of the baby. Disrupted growth and development disorders will occur if there are genetic or environmental factors that do not meet the basic needs of growth and development. One of the growth and development disorders in infants is weight gain and sleep patterns that are not sound. effort to optimize growth and development during the golden period in infants and is to provide good encouragement or stimulation to children. Parents can provide good encouragement or stimulation to children such as tactile stimulation in the form of baby massage. Community service aims to increase knowledge about the practice of infant massage. The subject of this activity is mothers who have babies and toddlers. This activity uses online/online/zoom media. carried out on Saturday, August 14 2022 via online/zoom media, the target target is mothers who have babies and toddlers as many as 15 mothers in Rt 13 Rw 13 Pisangan Timur Village, East Jakarta. The method consists of 3 stages: initial survey, implementation, evaluation. The results of the initial survey were mothers with poor knowledge of 33%, the implementation used the question-and-answer lecture method and demonstrations. The final evaluation is that the mother can practice massage on her baby and the mother has 100% good knowledge. It is hoped that this community service can provide insight to mothers about infant massage and be able to apply infant massage practices.

The Ability of Early Detection of Mental Health in Adolescents with the Provision of Health Education Using Audio Visual Methods at SMK Pawyatan Daha 1 Kediri

Background: Adolescent mental health is important in determining the quality of the nation. Early detection of mental health in adolescents is very necessary to provide knowledge and understanding and attention, to avoid and overcome the occurrence of disorders in the subsequent adolescent growth and development. Purpose: The purpose of this study is to determine the ability of early detection of mental health in adolescents with the provision of health education using audio visual. Methods: The design of this study is pre-experimental quantitative research with a one-group pre-post test design approach with the focus of the research directed at analyzing the effect of providing health education using audio-visual methods on the ability to early detection of mental health in adolescents at SMK Pawyatan Daha 1 Kediri. The total population was 394 respondents and a sample of 199 respondents were taken using the Stratifiet Random Sampling technique. Results: The findings found that before being given treatment, most respondents were less able to carry out early detection of mental health as many as 171 respondents (85.93%). After being given treatment, most respondents were able to carry out early detection of mental health as many as 158 respondents (79.40%). Based on the results of Wilcoxon's analysis, it was shown that the p-value of 0.000 < 0.05, then H0 was rejected and H1 was accepted so it was concluded that there was an influence of providing health education using audio-visual methods on the ability to early detection of mental health in adolescents at SMK Pawyatan Daha 1 Kediri. Conclusion: It is hoped that adolescents, especially students at SMK Pawyatan Daha 1 Kediri, can carry out early detection of mental health both to themselves and to others, which can reduce the risk of increased mental disorders or pressures experienced by adolescents.

Local application of engineered insulin-like growth factor I mRNA demonstrates regenerative therapeutic potential in vivo

Insulin-like growth factor I (IGF-I) is a growth-promoting anabolic hormone that fosters cell growth and tissue homeostasis. IGF-I deficiency is associated with several diseases, including growth disorders and neurological and musculoskeletal diseases due to impaired regeneration. Despite the vast regenerative potential of IGF-I, its unfavorable pharmacokinetic profile has prevented it from being used therapeutically. In this study, we resolved these challenges by the local administration of IGF-I mRNA, which ensures desirable homeostatic kinetics and non-systemic, local dose-dependent expression of IGF-I protein. Furthermore, IGF-I mRNA constructs were sequence engineered with heterologous signal peptides, which improved invitro protein secretion (2- to 6-fold) and accelerated invivo functional regeneration (16-fold) over endogenous IGF-I mRNA. The regenerative potential of engineered IGF-I mRNA was validated in a mouse myotoxic muscle injury and rabbit spinal disc herniation models. Engineered IGF-I mRNA had a half-life of 17-25h in muscle tissue and showed dose-dependent expression of IGF-I over 2-3days. Animal models confirm that locally administered IGF-I mRNA remained at the site of injection, contributing to the safety profile of mRNA-based treatment in regenerative medicine. In summary, we demonstrate that engineered IGF-I mRNA holds therapeutic potential with high clinical translatability in different diseases.

Novel therapies for growth disorders.

As we continue to understand more about the complex mechanism of growth, a plethora of novel therapies have recently been developed that aim to address barriers and optimize efficacy. This review aims to explore these novel therapies and provide a succinct review based on the latest clinical studies in order to introduce clinicians to therapies that will soon constitute the future in the field of short stature. Conclusion: The review focuses on long-acting growth hormone formulations, a novel growth hormone oral secretagogue, novel treatments for children with achondroplasia, and targeted therapies for rare forms of skeletal dysplasias. What is Known: • Recombinant human growth hormone has been the mainstay of treatment for children with short stature for years. • Such therapy is not always effective based on the underlying diagnosis (e.g achondroplasia, Turner syndrome). Compliance with daily injections is challenging and can directly affect efficacy. What is New: • Recent development of long-acting growth hormone regimens and oral secretagogues can overcome some of these barriers, however several limitations need to be taken into consideration. • Newer therapies for achondroplasia, and other rare forms of skeletal dysplasias introduce us to a new era of targeted therapies for children with short stature. Clinicians ought to be aware of pitfalls and caveats before introducing these novel therapies to every day practice.

Recurrence and Complication Rates of Surgical Treatment for Blount's Disease in Children: A Systematic Review and Meta-Analysis.

Blount's disease is a growth disorder of the proximal tibia that causes progressive genu varum in children. Surgical treatment is recommended if the deformity worsens, but which intervention is best remains controversial. This study aims to identify factors influencing outcomes and determine the most effective surgical approach. A systematic review was conducted of studies published before January 2022. In total, 63 retrospective studies with CEBM IIIb/IV levels were included (1672 knees in 1234 patients). The most commonly reported treatment was acute correction via osteotomy (47%), followed by hemiepiphysiodesis (22%) and gradual correction (18%). Combined procedures were reported in 13% of cases. The overall recurrence rate was 18%, with a significant difference when comparing the recurrence rates after gradual correction with those after hemiepiphysiodesis (7% and 29%, respectively). Major complications beyond recurrence were observed in 5% of cases. A meta-analysis of the available raw data showed a significantly increased recurrence rate (39%) among treated children who were between 4.5 and 11.25 years of age and were followed for a minimum follow-up of 2.5 years. Overall, poor evidence with which to establish an optimal treatment for Blount's disease was found. This study remarked on the need for early diagnosis, classification, and treatment of infantile tibia vara, since a significant rate of recurrence was found in neglected cases.

FAKTOR RISIKO LINGKUNGAN YANG BERHUBUNGAN DENGAN STUNTING PADA ANAK DI INDONESIA: LITERATUR REVIEW

Stunting is a disorder of growth and development of children due to chronic malnutrition and recurrent infections, which is characterized by the length or height below the standard. Indonesia is included in the third country with the highest prevalence in the Southeast Asia region. The results of the 2018 Basic Health Research (Riskesdas) show that the prevalence of stunting in under-five children in Indonesia is 30.8%. In 2022, through the Indonesian Nutrition Status Survey (SSGI) the stunting prevalence in under-five children in Indonesia has decreased to 21.6%. The purpose of this study was to determine environmental risk factors for stunting. The method in this study uses the literature review method by selecting data sources according to the desired topics and criterias. The database used in the source search is google scholar and ejournal.undip.ac.id, with the keywords water, sanitation, hygiene, and stunting. The results of studies from 10 scientific journals on environmental risk factors for stunting show that water, sanitation and hygiene are risk factors for stunting.

Surgical Treatment of Adolescent Idiopathic Scoliosis with the ApiFix Minimal Invasive Dynamic Correction System-A Preliminary Report of a 24-Month Follow-Up.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional growth disorder. Corrective surgical procedures are the recommended treatment option for a thoracic angle exceeding 50° and a lumbar major curve of 40°. Over the past few years, dynamic growth modulation implants have been developed as alternatives to permanent fusion. The ApiFix system was designed as a 2D "posterior dynamic device" for curve correction. After implantation in a minimally invasive procedure, it uses polyaxial joints and a self-adjusting rod to preserve the degree of motion and to accommodate the patient's growth. It provides an effective method of controlling deformity and fills the gap between the conservative treatment of major curves that are >35° and the fusion procedure. The objective of the two-center cohort study was the analysis of the correction results of patients, who underwent surgical intervention with the ApiFix system. The inclusion criteria were AIS, Lenke type 1 or type 5, a major curve on bending films of ≤30°, and an angle of the major curve of between 35° and 60°. Postoperative radiograph data were obtained longitudinally for up to 24 months of follow-up and compared to preoperative (preop) values. For comparisons of the different time points, non-parametric tests (Wilcoxon) or paired t-tests for normally distributed values were used to analyze repeated measures. Overall, 36 patients (25 female and 11 male) were treated with the ApiFix system from April 2018 to October 2020. Lenke type 1 was identified in 21 (58%) cases and Lenke type 5 was identified in 15 (42%) cases. The average angle of the thoracic major curve for Lenke 1 was 43°. The preoperative lumbar major curve (Lenke 5) was determined to be 43°. Over a follow-up of 24 months, a correction of the major curve to an average of 20° was observed for Lenke 1 and that to an average of 15° was observed for Lenke 5. Lenke type 1 and type 5 showed significant changes in the major curve over the individual test intervals in the paired comparisons compared to the starting angle (Lenke 1: preop-24 months, 0.002; Lenke 5: preop-24 months, 0.043). Overall, 11 events were recorded in the follow-up period, that required revision surgery. We distinguished between repeated interventions required after reaching the maximum distraction length of the implant due to the continued growth of the patient (n = 4) and complications, such as infections or problems associated with the anchorage of the implant (n = 7). The results from the present cohort revealed a statistically significant improvement in the postoperatively measured angles of the major and minor curves in the follow-up after 24 months. Consequently, the results were comparable to those of the already established vertebral body tethering method. Alignment in AIS via dynamic correction systems in combination with a possible growth modulation has been a treatment alternative to surgical fusing procedures for more than a decade. However, the long-term corrective effect has to be validated in further studies.

The influence of education by using 5J pregnancy nutrition guidebook for the prevention of fetal growth restriction and maternal nutritional sufficiency

Background: Stunting is a growth and development disorder experienced by children due to poor nutrition, recurring infections, and inadequate psychosocial stimulation. If not addressed with proper nutrition, it can lead to reduced child growth. According to the Indonesian Ministry of Health, stunting is influenced by several factors, including maternal, infant, and toddler factors, as well as social, economic, and environmental conditions. According to Global Nutrition, by 2025, it is estimated that children aged ≤ 5 years will experience stunting, with an increase of 171-314 million individuals worldwide, with 90% originating from countries in Africa and Asia. The province of Lampung has shown improvement, with a stunting prevalence of 15.2% in 2022, aiming to reach the national target of around 14%. Based on nutritional status monitoring in 2017, the prevalence of stunting was 35.20%, and according to the Indonesia Nutrition Status Study (INSS) and Community-Based Nutrition Recording and Reporting (CBNRP), the prevalence of stunting in Pesawaran in 2022 was 3.50%.Purpose: To determine the impact of using the 5J Pregnancy Nutrition Guidebook in educating pregnant mothers about preventing fetal growth restriction on the knowledge, attitudes, and behaviors of mothers in the working area of Gedong Tataan Community Health Center, Pesawaran, Lampung.Method: This quantitative research employed an analytical survey design with a quasi-experimental one-group pretest-posttest method. The dependent variables in this study were the level of knowledge, attitude, and behavior of mothers, while the independent variable was education using the 5J guidebook. The research was conducted in the Gedong Tataan Community Health Center, Pesawaran, Lampung in August 2023 with a sample size of 30 using total sampling technique, and a paired sample t-test was performed.Results: Knowledge improved by 2.37 points after receiving education, with an increase difference of 1.24, and the Wilcoxon statistical test yielded a p-value of 0.000 (<0.05). Respondents' attitudes increased by 1.93 points after receiving education, although this value was in the low range, it saw a rise with a difference of 0.9, and the p-value was 0.000 (<0.05). Behavior after receiving education increased to 1.23 with an increase difference of 0.2, and the Wilcoxon statistical test showed an improvement with a p-value of 0.000 (<0.05). The test results indicate the influence of education using the 5J guidebook on maternal knowledge, attitude, and behavior.Conclusion: Educational media using the 5J guidebook has a significant influence on maternal knowledge, attitude, and behavior regarding nutrition management in the prevention of stunting.

THU160 A Prospective Genetic Analysis Of Children With Idiopathic Short Stature (ISS) Using Whole-exome Sequencing (WES): First Results

Abstract Disclosure: L.D. Cellin: None. N.L. Menezes De Andrade: None. R.C. Rezende: None. V. Souza: None. N.C. Dantas: None. E. Quedas: None. M.F. Funari: None. G. Vasques: None. R.D. Scalco: None. A.C. Malaquias: None. A. Jorge: Consulting Fee; Self; Novo Nordisk. Grant Recipient; Self; BioMarin. Introduction: Children classified as idiopathic short stature (ISS) may have a monogenic cause that can explain their growth disorder. In this context, genetic tests emerge as a new diagnostic tool. Objectives: To determine the usefulness of WES for the genetic investigation of children with ISS. Patients and Methods: We sequentially enrolled 95 children with ISS without previous genetic testing, except for karyotyping for girls. In WES analysis, we prioritized rare variants (MAF<0.001), classified as loss-of-function (LoF) or missense predicted to be deleterious on in silico predictions. All variants were categorized according to ACMG/AMP criteria. We analyzed genes previously associated with growth disorders. CNV analysis was performed based on WES data; additionally, MLPA for SHOX was performed to assess deletion in regulatory regions. In positive cases, we carry out segregation in the family. Results: Our cohort was characterized by male preponderance (67%), markedly short stature (height SDS -2.6±0.7, 20% with height SDS<-3), and in 48% of cases, at least one of the parents have short stature. We identified 12 pathogenic or likely pathogenic (P/LP) variants by WES, including two gene deletions (SHOX and PTHLH) and 10 point mutations in ACAN (2x), IHH, PRKG2, LTBP3, ERF, THRA, GHR, PTPN11, and NF1. Additionally, two deletions involving the regulatory region of the SHOX gene were identified by MLPA. One patient had two P/LP alterations, totaling a diagnostic yield of 13.7% (12.6% if only WES results were considered). It is noteworthy that in addition to genes already associated with ISS (ACAN, SHOX, IHH, GHR, PTPN11, NF1), we observed a greater diversity of genes, including resistance to thyroid hormones (THRA) and milder forms of skeletal dysplasia (LTBP3, PTHLH, PRKG2). All but one of the variants were in the heterozygous state, including two de novo variants and four inherited from a parent with short stature. Fifteen patients have variants of uncertain significance (VUS) in genes already associated with growth disorder: IHH (3x), FGFR3 (2x), NPR2 (2x), LZTR1 (2x), MMP13, COL11A1, COL11A2, EXT2, IGF1R, and WNT5. Furthermore, four patients have variants of interest in new candidate genes (MAU2, MAP3K4, NR2E1, C6ORF136). Conclusion: The diagnostic yield was similar to other studies in children with ISS, but a greater diversity of genetic causes was observed, with those involving growth-plate genes and the RAS-MAPK pathway being more frequent. The large number of VUS highlights the need for further studies and new tools to classify these variants definitively. Presentation: Thursday, June 15, 2023

THU048 Determination Of Receptor Binding Affinity Of Growth Hormone Analogues To The Growth Hormone Receptor In A Drug Screening Context

Abstract Disclosure: S. Erlendsson: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. A. Kulakova: Employee; Self; Novo Nordisk. S. Poulsen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. P. Thygesen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Growth hormone (GH) and GH analogues are characterized by their ability to bind and activate the GH receptor (GHR). Binding affinity and functional activity are pivotal parameters for development and characterization of new GH analogues for treatment of growth disorders. The GHR is a member of the class I cytokine family and obtains a tripartite structure consisting of two extracellular fibronectin type III domains (ECD), a single-pass transmembrane domain (TMD), and a disordered intracellular domain (ICD). These receptors lack intrinsic kinase activity but rely on recruitment of intracellular signalling kinases and regulatory proteins. Activation of the downstream JAK-STAT signalling cascade is initiated by formation of an asymmetric GHR dimer induced by binding of GH to the GHR ECDs via two partially overlapping binding sites designated site I and II. The structural rearrangement in the ECDs propagates through the TMD and results in a separation of the ICDs which leads to activation through cross-phosphorylation of the Janus kinases 2 (JAK2). Here we utilize isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and small angle x-ray scattering (SAXS) to characterize the binding of native GH and GH analogues including somapacitan and pegvisomant to the monomeric GHR as well as an artificial soluble stabilized dimeric GHR. The GH analogues with good binding properties were subsequently tested in vitro for biological activity using a STAT3-luciferase reporter gene assay (RGA) and a proliferation assay with BAF3 cells expressing the human GHR. Both assays were established in two formats enabling testing of both receptor agonists and antagonists. Using SPR we show that the binding of all tested compounds is preserved between the monomeric and dimeric GHR with affinities ranging from near-picomolar to lower micromolar and we are subsequently able to confirm the expected stoichiometry by utilizing a combination of ITC and SAXS. In the RGA and the proliferation assay we demonstrate that a 1:2 stoichiometry is critical for receptor activation regardless of the affinity and therefore we propose high throughput screening of receptor stoichiometry as key in discovery of new growth disorder therapeutics. Presentation: Thursday, June 15, 2023

FRI020 Adipocyte Subpopulations Regulate Growth Hormone-induced Lipolysis And Insulin Resistance

Abstract Disclosure: S. Siyar: None. J. Huang: None. R. Sharma: None. J.J. Kopchick: None. V. Puri: None. K.Y. Lee: None. Growth Hormone (GH) administration has long been known to increase lipolysis in adipose tissue leading to increased circulating free fatty acid levels and insulin resistance. Previous studies from our lab have found that this effect is mediated, at least in part, through transcriptional repression of the lipid droplet associated protein Fat specific protein (FSP27 also known as CIDEC). Furthermore, recent studies suggest that within a single adipose tissue depot there are different subpopulations of adipocytes. We have identified three distinct subpopulations of adipocytes with unique gene expression profiles and metabolic activities. We have found that one of these subpopulations of adipocytes, termed Type 2 adipocytes, are highly responsive to GH stimulation. In order to assess the physiological role of GH-mediated lipolysis mediated by this subpopulation, we specifically expressed human FSP27 (hFSP27) in Type 2 adipocytes (Type2Ad-hFSP27tg mice). Type2AdhFSP27tg mice had reduced systemic plasma glycerol release after acute GH treatment, and improvement in acute, but not chronic, GH-induced glucose intolerance. These mice exhibited an 45% increase in fat mass and significant increase in adipocyte cell size further indicating a decreased lipolytic response to GH. This decreased lipolytic response was associated with improved hepatic insulin signaling and insulin-induced gene expression in Type2Ad-hFSP27tg mice. Taken together, these results indicate that specifically targeting a subpopulation of adipocytes is sufficient to reduce GH-induced lipolysis and insulin resistance and may provide a platform for improved medical therapies for growth and endocrine disorders. Presentation: Friday, June 16, 2023

THU166 A Minimum Data Set For The Monitoring Of Recombinant Human Growth Hormone (rhGH) Therapy In Children With Growth Hormone Deficiency (GHD)—A GloBE-Reg Initiative

Abstract Disclosure: S.C. Chen: None. E. Charmandari: None. J. Choi: None. X. Dou: None. C. Gong: None. R. Hamza: None. J. Harvey: None. A.R. Hoffman: None. R. Horikawa: None. G. Johannsson: None. A.A. Jorge: None. B.S. Miller: None. S. Roehrich: None. L.S. Savendahl: None. X. Tserotopolou: None. M.P. Wajnrajch: None. S.F. Ahmed: Grant Recipient; Self; Novo Nordisk. Objective Although there are some recommendations in the literature on the assessments that should be performed in children on rhGH therapy, the level of consensus on these measurements and their frequency for routine clinical practice is unclear. The objective of this study was to identify a minimum dataset (MDS) to be captured in routine clinical settings for children receiving all forms of rhGH therapy for GH deficiency (GHD). Methods This exercise was undertaken through the collaborative efforts of a group of experts who form the GH Scientific Study Group (SSG) in GloBE-Reg, a new international registry platform developed in close collaboration with clinicians, patients and industry and which can support long-term safety and effectiveness studies for drugs that require such surveillance. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, two patient advocates and representatives from two industry partners with previous GH registry expertise developed a comprehensive list of data fields routinely collected for children with GHD. Members graded the: (1) Importance of the field and (2) Ease of data collection. Fields that achieved a minimum of 70% consensus for importance qualified for the MDS, provided <50% deemed the item difficult to collect. Results Of 225 items graded, 113 (50%) items achieved at least 70% consensus as important to collect. Of the 225 items, 69 (31%) were deemed easy to collect and combining the criteria of importance and ease of data collection, 64 (28%) met both criteria for the MDS. Some other items including patient involvement in clinical trials, HbA1c in long-acting rhGH therapy and adherence did not meet the MDS criteria but were considered to be important enough to be included and some of the items were merged into one item. The final MDS consisted of 43 items; 20 to be entered once, 14 every 6 months and 9 every 12 months. Conclusions In summary, this exercise formulated the minimum dataset for the GloBE-Reg GH module which was launched in October 2022 for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and also the newer long-acting growth hormone. Additional modules are being developed for specific GH products and other therapies for growth disorders. More information about the study and instructions on how to participate are available on the project’s website: www.globe-reg.net. Presentation: Thursday, June 15, 2023