{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:12:44Z","timestamp":1792843964006,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002713","name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University","doi-asserted-by":"publisher","award":["IMSU-DDRSP2501"],"award-info":[{"award-number":["IMSU-DDRSP2501"]}],"id":[{"id":"10.13039\/501100002713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Childhood growth hormone deficiency (GHD) and idiopathic short stature (ISS) are endocrine disorders characterized by impaired linear growth due to insufficient or ineffective growth hormone (GH) activity. While daily recombinant human GH (rhGH) therapy effectively restores growth, treatment adherence remains suboptimal owing to the burden of daily injections. Long-acting formulations such as pegylated recombinant human GH (PEG-rhGH) have been developed to improve convenience and compliance while maintaining therapeutic efficacy. This systematic review and meta-analysis aimed to evaluate the comparative effectiveness and safety of once-weekly PEG-rhGH versus daily rhGH and to assess dose\u2013response outcomes between higher- and lower-dose PEG-rhGH regimens in pediatric GHD and ISS. Methods: This study followed PRISMA 2020 guidelines. Comprehensive searches were conducted in PubMed, Web of Science, and Scopus from inception to September 2025 using MeSH terms and free-text keywords for \u201cPEGylated recombinant human growth hormone,\u201d \u201clong-acting growth hormone,\u201d and \u201cgrowth hormone deficiency.\u201d Eligible studies included randomized controlled trials (RCTs) and cohort studies evaluating PEG-rhGH in children (\u226418 years) with GHD or ISS, comparing either once-weekly PEG-rhGH with daily rhGH or different PEG-rhGH doses. Data extraction included study design, participant characteristics, intervention details, and key outcomes (height SDS, height velocity, IGF-1 SDS). Meta-analysis was conducted using Review Manager with a random-effects model, and heterogeneity was quantified using the I2 statistic. Results: Eight studies, comprising 2549 children, met the inclusion criteria. Once-weekly PEG-rhGH demonstrated comparable short-term growth outcomes to daily rhGH at 6 and 12 months, with modest but significant superiority in height SDS (MD = 0.10, 95% CI 0.01\u20130.19) and height velocity (MD = 0.74 cm\/year, 95% CI 0.42\u20131.05) by 24 months. IGF-1 SDS did not differ significantly at 6 or 12 months. In dose comparisons, 0.2 mg\/kg\/week PEG-rhGH produced substantially greater gains in height SDS and IGF-1 SDS than 0.1 mg\/kg\/week, with a time-dependent increase in the magnitude of the effect. Safety analyses revealed no increase in adverse or serious adverse events with PEG-rhGH compared to daily rhGH; reactions were generally mild and transient. Conclusions: Once-weekly PEG-rhGH is as effective as daily rhGH for promoting growth in pediatric GHD and ISS, with possible long-term advantages in growth outcomes and similar safety. The higher PEG-rhGH dose (0.2 mg\/kg\/week) appears to optimize efficacy without compromising tolerability. Weekly administration may enhance adherence and quality of life, supporting PEG-rhGH as a viable alternative to daily GH therapy.<\/jats:p>","DOI":"10.3390\/jcm14248740","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T16:11:18Z","timestamp":1765383078000},"page":"8740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative Efficacy and Safety of Once-Weekly Pegylated Recombinant Human Growth Hormone Versus Daily Growth Hormone Therapy in Children: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Bassam","family":"Bin-Abbas","sequence":"first","affiliation":[{"name":"Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mosleh Ali","family":"Jabari","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11564, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000452150","article-title":"Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency","volume":"86","author":"Grimberg","year":"2016","journal-title":"Horm. 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