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Scientific Reports Apr 2024The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal... (Meta-Analysis)
Meta-Analysis
The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.
Topics: Child; Humans; Growth Hormone; Network Meta-Analysis; Human Growth Hormone; Dwarfism, Pituitary; Growth Disorders; Hormone Replacement Therapy
PubMed: 38580693
DOI: 10.1038/s41598-024-58616-4 -
Frontiers in Endocrinology 2023Growth hormone (GH) is crucial to growth and development. GH secretion is regulated by a complex feedback system involving the pituitary gland, hypothalamus, and other... (Review)
Review
Growth hormone (GH) is crucial to growth and development. GH secretion is regulated by a complex feedback system involving the pituitary gland, hypothalamus, and other organs, and predominantly occurs during deep sleep. Isolated and idiopathic growth hormone deficiency (GHD) is a condition characterized by GHD without any other signs or symptoms associated with a specific syndrome or disease. The aim of this narrative review was to evaluate the relationship between GH and sleep in children using published data. Various databases (Medline/PubMed, Scopus, and Web of Science) were systematically searched for relevant English language articles published up to April 2023. Search strategies included the terms 'children/pediatric', 'growth hormone', 'growth hormone deficiency' and 'sleep'. Data were extracted by two independent reviewers; 185 papers were identified of which 58 were duplicates and 118 were excluded (unrelated n=83, syndromic/genetic GHD n=17, non-English n=13, abstract n=1, case report n=1). Overall, nine studies (six clinical studies, two case series, and one survey) were included. GHD appears to have an adverse effect on sleep in children, and GH therapy has only been shown to have a beneficial effect on sleep parameters in some individuals. Notably, identified data were limited, old/poor quality, and heterogenous/inconsistent. Further research of GHD in pediatric populations is necessary to improve the understanding of GHD impact on sleep and its underlying mechanisms, and to determine the specific impacts of GH therapy on sleep in children.
Topics: Humans; Child; Growth Hormone; Human Growth Hormone; Hypopituitarism; Dwarfism, Pituitary; Sleep
PubMed: 38327902
DOI: 10.3389/fendo.2023.1332114 -
European Journal of Medical Genetics Nov 2023The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical,...
The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5-6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the striking features of achondroplasia.
Topics: Adolescent; Humans; Child; Adult; Quality of Life; Chronic Pain; Achondroplasia
PubMed: 37758167
DOI: 10.1016/j.ejmg.2023.104850 -
Journal of Neurosurgery. Pediatrics Nov 2023Pediatric achondroplasia is often associated with conditions requiring neurosurgical intervention, including CSF diversion and multilevel spinal decompression. However,...
OBJECTIVE
Pediatric achondroplasia is often associated with conditions requiring neurosurgical intervention, including CSF diversion and multilevel spinal decompression. However, there is a lack of clinical guidelines and reliable estimates of the benefits and risks of these interventions. This study aimed to summarize the literature on the neurosurgical management of pediatric achondroplasia patients in order to aid in determining optimal treatment and standardization of care.
METHODS
A systematic review of peer-reviewed studies with an objective diagnosis of achondroplasia, patient demographic information, and available data on neurosurgical interventions performed before 18 years of age for cervicomedullary compression, spinal stenosis, and hydrocephalus was performed. Study quality and risks of bias were assessed using standardized scores. Independent patient data on surgical indications, outcomes, reoperations, and complication risks were aggregated using means and percentages.
RESULTS
Of 204 records, 25 studies with 287 pediatric achondroplasia patients (mean age 25 ± 36 months) treated for cervicomedullary compression (n = 153), spinal stenosis (n = 100), and obstructive hydrocephalus (n = 34) were evaluated. Symptomatic cervicomedullary compression occurred early in life (mean age 31 ± 25 months), with apnea (48%), T2-weighted MRI cord signal (28%), myelopathy (27%), and delayed motor skills (15%) requiring foramen magnum decompression observed in 99% of patients, as well as cervical laminectomy in 65% of patients. Although 91% of treated patients had resolution of symptoms, 2% mortality, 9% reoperation, and 21% complication rates were reported. Spinal stenosis was treated in relatively older children (mean age 13 ± 3 years) with laminectomy (23%), as well as with instrumented fusion (73%) for neurogenic claudication (59%), back pain (15%), and sciatica (8%). Although 95% of patients had symptom resolution after surgery, 17% reported complications and 18% required reoperation. Of the hydrocephalus patients (mean age 56 ± 103 months), half were treated with endoscopic third ventriculostomy (ETV) and half had a shunt placed for progressive ventriculomegaly (66%), headaches (32%), and delayed cognitive development (4%). The shunted patients had a 3% mortality rate and an average of 1.5 shunt revisions per patient. None of the patients who underwent ETV as the primary procedure required a revision.
CONCLUSIONS
Neurosurgical intervention for pediatric achondroplasia conditions, including cervicomedullary compression, spinal stenosis, and hydrocephalus, is associated with high recovery rates and good outcomes. However, complications and reoperations are common. Further studies with follow-up into adulthood are needed to evaluate the long-term outcomes.
Topics: Child; Humans; Infant; Adolescent; Child, Preschool; Spinal Stenosis; Retrospective Studies; Laminectomy; Hydrocephalus; Achondroplasia
PubMed: 37728398
DOI: 10.3171/2023.6.PEDS23162 -
Growth Hormone & IGF Research :... Aug 2023Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe...
UNLABELLED
Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15.
SUBJECT AND METHOD
We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized.
RESULTS
Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was -5.1(-5.9/-4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year).
CONCLUSION
GH seems to be effective for r(15) syndrome patients with short stature.
Topics: Child; Humans; Child, Preschool; Human Growth Hormone; Growth Hormone; Ring Chromosomes; Growth Disorders; Dwarfism; Syndrome
PubMed: 37531800
DOI: 10.1016/j.ghir.2023.101550 -
Advances in Therapy Sep 2023Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment... (Review)
Review
BACKGROUND
Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment landscape of the condition. This systematic literature review (SLR) aimed to identify health-related quality of life (HRQoL)/utilities, healthcare resource use (HCRU), costs, efficacy, safety and economic evaluation data in achondroplasia and to identify gaps in the research.
METHODS
Searches of MEDLINE, Embase, the University of York Centre for Reviews and Dissemination (CRD), the Cochrane Library and grey literature were performed. Articles were screened against pre-specified eligibility criteria by two individuals and study quality was assessed using published checklists. Additional targeted searches were conducted to identify management guidelines.
RESULTS
Fifty-nine unique studies were included. Results demonstrated a substantial HRQoL and HCRU/cost-related burden of achondroplasia on affected individuals and their families throughout their lifetimes, particularly in emotional wellbeing and hospitalisation costs and resource use. Vosoritide, growth hormone (GH) and limb lengthening all conferred benefits for height or growth velocity; however, the long-term effects of GH therapy were unclear, data for vosoritide were from a limited number of studies, and limb lengthening was associated with complications. Included management guidelines varied widely in their scope, with the first global effort to standardise achondroplasia management represented by the International Achondroplasia Consensus Statement published at the end of 2021. Current evidence gaps include a lack of utility and cost-effectiveness data for achondroplasia and its treatments.
CONCLUSIONS
This SLR provides a comprehensive overview of the current burden and treatment landscape for achondroplasia, along with areas where evidence is lacking. This review should be updated as new evidence becomes available on emerging therapies.
Topics: Humans; Quality of Life; Achondroplasia; Human Growth Hormone; Cost-Benefit Analysis
PubMed: 37382866
DOI: 10.1007/s12325-023-02549-3 -
Genetics in Medicine : Official Journal... Oct 2023Skeletal dysplasia are heterogeneous conditions affecting the skeleton. Common nutrition issues include feeding difficulties, obesity, and metabolic complications. This...
PURPOSE
Skeletal dysplasia are heterogeneous conditions affecting the skeleton. Common nutrition issues include feeding difficulties, obesity, and metabolic complications. This systematic scoping review aimed to identify key nutrition issues, management strategies, and gaps in knowledge regarding nutrition in skeletal dysplasia.
METHODS
The databases Ovid MEDLINE, Ovid EMBASE, Ebsco CINAHL, Scopus, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews were searched. Reference lists and citing literature for included studies were searched. Eligible studies included participants with skeletal dysplasia and described: anthropometry, body composition, nutrition-related biochemistry, clinical issues, dietary intake, measured energy or nutrition requirements, or nutrition interventions.
RESULTS
The literature search identified 8509 references from which 138 studies were included (130 observational, 3 intervention, 2 systematic reviews, and 3 clinical guidelines). Across 17 diagnoses identified, most studies described osteogenesis imperfecta (n = 50) and achondroplasia or hypochondroplasia (n = 47). Nutrition-related clinical issues, biochemistry, obesity, and metabolic complications were most commonly reported, and few studies measured energy requirements (n = 5).
CONCLUSION
Nutrition-related comorbidities are documented in skeletal dysplasia; yet, evidence to guide management is scarce. Evidence describing nutrition in rarer skeletal dysplasia conditions is lacking. Advances in skeletal dysplasia nutrition knowledge is needed to optimize broader health outcomes.
Topics: Humans; Comorbidity; Dwarfism; Obesity; Osteochondrodysplasias; Systematic Reviews as Topic
PubMed: 37330695
DOI: 10.1016/j.gim.2023.100920 -
Pharmacological Research Jul 2023We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations... (Meta-Analysis)
Meta-Analysis Review
Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.
We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.
Topics: Humans; Child; Human Growth Hormone; Growth Hormone; Quality of Life; Cost-Benefit Analysis; Dwarfism, Pituitary; Hormone Replacement Therapy
PubMed: 37236413
DOI: 10.1016/j.phrs.2023.106805 -
Frontiers in Endocrinology 2023To investigate the efficacy of monotherapy with AIs or GnRHa in improving the height of boys with idiopathic short stature (ISS). (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aromatase inhibitors and gonadotropin-releasing hormone analogue in increasing final height of idiopathic short stature boys: a network meta-analysis.
OBJECTIVE
To investigate the efficacy of monotherapy with AIs or GnRHa in improving the height of boys with idiopathic short stature (ISS).
METHOD
We performed a systematic search in Pubmed, The Cochrane Library, Chinese National Knowledge Infrastructure databases, and Wanfang Database for eligible studies. The network meta-analysis was conducted using STATA software.
RESULTS
We identified a total of four studies that included 136 individuals. We used FAH/PAH as the main outcome of final height. The results revealed a statistically higher final height after treatment with AI or GnRHa in idiopathic short stature children(MD= 4.63, 95% CI[3.29,5.96]). In network meta-analysis, the direct and indirect comparison between AI and GnRHa was presented in the forest plot. Compared with control group, both AI and GnRHa were effective in increasing the final height, with the mean effect of 4.91(95%CI:1.10,8.17) and 5.55(95%CI:1.12,9.98) respectively. However, there was no statistical difference between the GnRHa and AI treatment, of which the mean effect was 0.65(95%CI: -4.30,5.60).
CONCLUSION
Both AIs and GnRHa monotherapy were effective in augmenting the final height of boys with idiopathic short stature when compared to placebo groups. However, there was no statistical difference between the GnRHa and AI treatments.
Topics: Male; Child; Humans; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Network Meta-Analysis; Body Height; Human Growth Hormone; Dwarfism
PubMed: 37124748
DOI: 10.3389/fendo.2023.1167351 -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578