Growth Hormone Dose Modulation and Final Height in Short Children Born Small for Gestational Age: French Real-Life Data

Abstract

Introduction Growth hormone (GH) therapy improves height outcomes in short children born small for gestational age (SGA); however, real-world data on long-term GH exposure are few. Methods We report results from an observational study (NCT01578135) including children born SGA, treated with GH at 126 sites in France and followed-up for >5 years until achieving final adult height (FAH) or until study termination. Primary endpoints were the proportion of patients with normal (>−2) height standard deviation score (SDS) at last visit and with normal FAH SDS. Post hoc analyses were performed by multivariate logistic regression analysis with stepwise elimination to identify factors associated with GH dose modulation and normal height SDS achievement. Results Of 1408 registered patients, a representative sample (n = 291) was selected for long-term follow-up. At last visit, 193/291 (66.3%) children achieved normal height SDS and 72/291 (24.7%) reached FAH. FAH SDS was >–2 for chronological age in 48 (66.7%) children and >–2 for adult age in 40 (55.6%) children. In the post hoc analyses, height SDS at last visit was a significant determinant of whether GH dose had been modulated. Factors significantly associated with reaching normal height SDS were baseline height SDS (taller, better), age at treatment start (younger, better), treatment duration excluding discontinuation periods (longer, better) and absence of a chronic disease. Most (70%) adverse events were non-serious, with 39% considered possibly/probably related to GH treatment. Conclusions GH therapy was fairly effective in most short children born SGA. No new safety concerns were identified.

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

“…In conclusion, the Real-life experience reported by Coutant and his colleagues [1] reinforces the use of GH as a safe mode of treatment in previously SGA children. Consistent with the recently published 2023 consensus guidelines [11], management entails starting treatment at the recommended dosage of 33-67 μg/kg/day from 3 to 4 years old in children who have failed to show catch-up growth.…”

“…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.…”

“…To make matters more complicated, the third baby has poor foetal growth, but size at birth is above −2 SD, so this baby has IUGR but no actual SGA. Such a baby would not be detected using the −2 SD cut-off chosen for the study of Coutant et al [1] and raises the question as to what percentile or SD cut-off should be chosen when birth weight is used for short stature screening [7].…”

“…Consistent with the recently published 2023 consensus guidelines [11], management entails starting treatment at the recommended dosage of 33-67 μg/kg/day from 3 to 4 years old in children who have failed to show catch-up growth. Coutant et al's [1] data show that clinicians are modulating GH dose responsibly and appropriately in relation to response to GH treatment. In practice, many families in this "Real-life" study discontinued GH therapy…”