Is Growth Hormone Therapy for Previously Small for Gestational Age Safe and Effective? Commentary on Results from the 2005–2018 French National Registry

Abstract

Short children who were previously born small for gestational age (SGA) constitute a challenging group for the clinician. Among the SGA population who remain short, defined as two standard deviations below the population mean (−2 SD), which children are simply small but normal? Which children are short because of an actual growth disorder resulting in intrauterine growth restriction (IUGR), otherwise called foetal growth restriction (FGR)? And in which children is the short stature unrelated to the previous SGA, but due to other causes such as growth hormone (GH) deficiency? Concerning treatment, SGA is a licensed indication for GH therapy, but which patients should be selected for treatment, in what dose, and at what age? Most importantly, is GH treatment for SGA children safe?This commentary attempts to discuss at least some of these questions in the light of results from an impressive cohort study from the French National SGA Registry (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) of patients receiving daily injections of GH for SGA. In their "Real-life" paper, published in this edition of Hormone Research in Paediatrics, Coutant et al. [1] from Angers, Lyon, Nancy, and Toulouse, respectively, take an honest and comprehensive look at outcome in a representative sample of 1 in 5 patients taken from the 1,408 patients registered between 2005 and 2010 and followed up until 2018. Inclusion criteria were simply SGA, defined as birth weight and/or birth length below minus two standard deviations (−2 SD) of the French population data of Sempé [2]; and ongoing treatment with daily Norditropin injections for short stature. In keeping with the "Real-life" ethos of the study, patients with chronic diseases such as asthma and genetic disorders were not excluded.In terms of the safety of GH therapy, Coutant et al.'s [1] data give welcome reassurance. Of the 291 patients selected for study, in whom median duration of GH treatment was 5.5 years, 86 serious adverse events were reported in 46 patients. Of these, an association with GH was considered probable in only three, possible in three, indeterminate in 7, and unlikely in 73. No new safety concerns arose during the study. These results are encouraging for GH-treated SGA patients and their families within and beyond Europe, and to some extent for all patients receiving GH. Of course, full assurance as to the long-term safety of GH treatment requires continuing follow-up and appraisal of adult health status, including insulin-glucose kinetics, cardiac and vascular wellbeing, and cancer prevalence. This important area of research was clearly outside the scope of the French registry, which closed in 2018. However, their data do add to a growing body of observational studies including recent work from Sävendahl and colleagues [3], reinforcing the remarkably good safety profile of GH treatment.If we can be reassured that giving GH to previously SGA children is safe, is it effective? In terms of short-term response, the answer from the prese...