ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Pediatric Endocrinology
Determinants of adverse event occurrence in children with short stature born small for gestational age treated with growth hormone
Provisionally accepted
- 1Department of Paediatric Medicine, University Hospital Angers, Angers, France
- 2Rare Endocrine Disorders, Clinical Medical and Regulatory, Novo Nordisk, Paris, France
- 3AP-HP, Paris Saclay University, INSERM, Physiologie et Physiopathologie Endocriniennes, Endocrinology and Diabetology for Children, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicetre, France
- 4Division of Pediatric Endocrinology and Metabolism, Lyon University Pediatric Hospital, Lyon, France
- 5Endocrinology and Bone Diseases Unit, Children’s Hospital, Toulouse University Hospital, University of Toulouse Paul Sabatier, INSERM-CNRS Unit 1291, Infinity Center, Toulouse, France
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ABSTRACT (250/250 words) Introduction Recombinant human growth hormone (rhGH) treatment for short children born small for gestational age (SGA) is effective in improving height outcomes. Determinants of height response to rhGH treatment have been identified using multiple regression analyses. Although adverse events (AEs) associated with treatment have been described, determinants of AE occurrence are not well known. Methods This analysis used safety data collected between 2007 and 2018 in an observational, prospective registry study (NCT01578135) including children born SGA across 126 sites in France. AEs were reported by patients or recorded by treating physicians. Univariate and multivariate analyses were performed to identify determinants of occurrence of AEs and serious AEs (SAEs). Results Of 291 patients from the registry, 287 AEs were reported in 149 (51.2%) patients. Each patient experienced a mean of 0.205 AEs per patient-year (range 0–4.3) and a mean of 0.054 SAEs (range 0–1.8). The most frequently reported AEs were headache (9.3%) and arthralgia (4.5%). Using multiple regression analyses, longer registry participation (p=0.0146, odds ratio [OR]=1.98), presence of chronic disease (p=0.0004, OR=2.56), and concomitant treatment (p=0.0162, OR=1.79) were associated with increased risk of experiencing AEs. GH dose at inclusion or cumulative GH dose during first 2 years of treatment were not associated with AE risk, while higher GH dose at last visit was associated with reduced risk (p=0.0412, OR=0.58). Conclusions In short children born SGA, underlying conditions and associated treatments seem to be the main factors associated with AE occurrence, while GH dose was inversely related to AE occurrence.
Keywords: Growth Hormone, small for gestational age, adverse events, serious adverse events, Real-world data
Received: 30 Jun 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Coutant, Benchikh, Linglart, Nicolino and Salles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Regis Coutant, recoutant@chu-angers.fr
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