Pubertal growth in children born small for gestational age (SGA) with persistent short stature (SGA-SS). Growth hormone treatment outcomes from data of the Czech countywide REPAR database
Authors:
Kodytková Aneta 1,LedjonaToni 1; Plachý Lukáš 1; Jírová Barbora 1; Hainerová Aldhoon Irena 2; Aleksijevi Darina 3; Černá Jana 4; Dvořáková Marcela 5; El-Lababidi Eva 2; Kalvachová Božena 5; Kocourková Kamila 6; Kotvalová Ivana 7; Magnová Olga 8; Novotná Dana 8; Obermannová Barbora 1; Pomahačová Renata 9; Průhová Štěpánka 1; Souček Ondřej 1; Strnadel Jiří 4; Šíchová Lucie 10; Škvor Jaroslav 10; Šnajderová Marta 1; Šumník Zdeněk 1; Zapletalová Jiřina 3; Šilar Jiří 11; Koloušková Stanislava 1; Lebl Jan 1
Authors‘ workplace:
Pediatrická klinika, 2. lékařská fakulta, Univerzita Karlova a Fakultní nemocnice v Motole, Praha
1; Klinika dětí a dorostu, 3. lékařská fakulta, Univerzita Karlova a Fakultní nemocnice Královské Vinohrady, Praha 3 Dětská klinika, Lékařská fakulta, Univerzita Palackého a Fakultní nemocnice Olomouc
2; Klinika dětského lékařství, Lékařská fakulta, Ostravská univerzita a Fakultní nemocnice Ostrava
4; Endokrinologický ústav, Praha
5; Dětské oddělení, Nemocnice České Budějovice
6; Dětská klinika, Lékařská fakulta, Univerzita Karlova a Fakultní nemocnice Hradec Králové
7; Pediatrická klinika, Lékařská fakulta, Masarykova univerzita a Fakultní nemocnice Brno
8; Dětská klinika, Lékařská fakulta, Univerzita Karlova a Fakultní nemocnice Plzeň
9; Dětská klinika, Masarykova nemocnice, Krajská zdravotní, a. s., Ústí nad Labem
10; Institut biostatistiky a analýz, s. r. o., Brno, #tyto dvě autorky přispěly kevzniku článku stejným dílem
11
Published in:
Čes-slov Pediat 2023; 78 (S3): 30-36.
Category:
Original Papers
doi:
https://doi.org/10.55095/CSPediatrie2023/058
Overview
Both pre-pubertal growth and magnitude of the pubertal growth spurt are the prerequisites of potential of growth hormone therapy to optimize final height. We analyzed impact of pre-pubertal and pubertal growth components on the total effect of growth hormone therapy in a cohort of 397 children (221 boys) registered in the Czech national database of growth hormone recipients REPAR. All were born small for gestational age, had persistent short stature in childhood (SGA-SS) and already achieved their near-final height. We separately evaluated children according to parental heights (with both parents over −2 ht-SDS, one below −2 ht-SDS, both below −2 ht-SDS) and according to their size at birth – low birth weight, low birth length, low both parameters.
Up to treatment completion, treatment led to a height gain of 1,59 ht-SDS; of this, the pre-pubertal gain was 1,57 ht-SDS. Thus, ht-SDS remained unchanged within puberty, despite continuous growth hormone administration. The final ht-SDS gain adjusted for age 18 years was 0,91 (all three parameters p<0.0001 if compared to pre-treatment). Children with both parents taller than −2 SD and children with exclusively low birth weight had significantly better treatment outcomes.
Analysis results of the REPAR database confirm efficacy of growth hormone therapy in SGA-SS children. The treatment success is based on pre-pubertal growth component. Therefore, a careful follow-up of children born SGA and a timely initiation of growth hormone therapy in early childhood are of crucial importance.
Keywords:
small-for-gestational-age, SGA-SS, growth hormone, puberty, pubertal growth spurt, adult height
Sources
1. Karlberg J. On the modelling of human growth. Stat Med 1987; 6: 185–92.
2. Carel JC. Management of short stature with GnRH agonist and co-treatment with growth hormone: a controversial issue. Mol Cell Endocrinol 2006; 254–255: 226–233.
3. Carrascosa Lezcano A, Fernández García JM, Fernández Ramos C, et al. Spanish cross-sectional growth study 2008. Part II. Height, weight and body mass index values from birth to adulthood. An Pediatr 2008; 68: 552–569.
4. Bláha P, Vignerová J, Riedlová J, et al. VI. celostátní antropologický výzkum dětí a mládeže 2001. Ces-Slov Pediat 2003; 58: 766–770.
5. Toni L, Kodytková A, Plachý L, et al. Dospělá výška dětí, které se narodily malé na svůj gestační věk (SGA) s malou výškou v dětství (SGA-SS). Výsledky léčby růstovým hormonem z dat české národní databáze REPAR. Ces-Slov Pediat 2023; 78 (S3): S22–29.
6. Adler E, Lambert A-S, Bouvattier C, et al. Determinants of final height in patients born small for gestational age treated with recombinant growth hormone. Horm Res Paediatr 2021; 94: 52–62.
7. van der Steen M, Lem AJ, van der Kaay DC, et al. Puberty and pubertal growth in GH-treated SGA children: effects of 2 years of GnRHa versus no GnRHa. J Clin Endocrinol Metab 2016; 101: 26964733.
8. Tanaka T, Yokoya S, Seino Y, et al. Onset of puberty and near adult height in short children born small for gestational age and treated with GH: interim analysis of up to 10 years of treatment in Japan. Clin Pediatr Endocrinol 2015; 24: 15–25.
9. de Ridder MAJ, Stijnen T, Hokken-Koelega ACS. Prediction model for adult height of small for gestational age children at the start of growth hormone treatment. J Clin Endocrinol Metab 2008; 93: 477–483.
10. Lebl J, Krásničanová H. Růst dětí a jeho poruchy. Praha: Galén 1996
11. Newton PT, Li L, Zhou B, et al. A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate. Nature 2019; 567(7747): 234–238.
12. Lebl J, Plachý L, Toni L, et al. Mysteria skeletálního růstu: Jak růstová chrupavka určuje tělesnou výšku. In: Onemocnění skeletu u dětí. Motolské pediatrické semináře 4. Praha: Galén 2019: 99–115.
13. Emons J, Chagin AS, Sävendahl L, et al. Mechanisms of growth plate maturation and epiphyseal fusion. Horm Res Paediatr 2011; 75: 383–391.
14. Weise M, De-Levi S, Barnes KM, et al. Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci USA 2001; 98: 6871–6876.
15. Plachy L, Strakova V, Elblova L, et al. High prevalence of growth plate gene variants in children with familial short stature treated with growth hormone. J Clin Endocrinol Metab 2019; 104: 4273–4281.
16. Shuhaibar LC, Robinson JW, Vigone G, et al. Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor. eLife 2017; 6: pii: e31343.
17. Vasques GA, Arnhold IJ, Jorge AA. Role of the natriuretic peptide system in normal growth and growth disorders. Horm Res Paediatr 2014; 82: 222–229.
18. Wang SR, Jacobsen CM, Carmichael H, et al. Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature. Hum Mutat 2015; 36: 474–481.
19. Hodax JK, Quintos JB, Gruppuso PA, et al. Aggrecan is required for chondrocyte differentiation in ATDC5 chondroprogenitor cells. PLoS One 2019; 14: e0218399.
20. Tanner JM, Goldstein H, Whitehouse RH. Standards for children’s height at age 2–9 years allowing for height of parents. Arch Dis Child 1970; 45: 755–762.
21. Plachy L, Dusatkova P, Maratova K, et al. Familial short stature-a novel phenotype of growth plate collagenopathies. J Clin Endocrinol Metab 2021; 106: 1742–1749.
22. Plachy L, Dusatkova P, Maratova K, et al. NPR2 variants are frequent among children with familiar short stature and respond well to growth hormone therapy. J Clin Endocrinol Metab 2020; 105: dgaa037.
23. Ruiz RA, Pérez AB, Leiva-Gea I, et al. Factors influencing height gain in children born small for gestational age treated with recombinant growth hormone: what extent is puberty involved? Ther Adv Endocrinol Metab 2022; 13: 1–14.
24. Renes JS, Willemsen RH, Mulder JC, et al. New insights into factors influencing adult height in short SGA children: results of a large multicentre growth hormone trial. Clin Endocrinol 2015; 82: 854–861.
25. Boguszewski MCS, Carlsson M, Lindberg A, et al. Near-adult height after growth hormone treatment in children born prematurely – data from KIGS. J Clin Endocrinol Metab 2020; 105: 2457–2463.
26. Gaddas M, Périn L, Le Bouc Y. Evaluation of IGF1/IGFBP3 molar ratio as an effective tool for assessing the safety of growth hormone therapy in small-for-gestational-age, growth hormone-deficient and Prader-Willi children. J Clin Res Pediatr Endocrinol 2019; 11: 253–261.
27. Persson I, Ahlsson F, Ewald U, et al. Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases. Am J Epidemiol 1999; 150: 747–755.
28. Deng X, Li W, Luo Y, et al. Association between small fetuses and puberty timing: a systematic review and meta-analysis. Int J Environ Res Public Health 2017; 14: 1377.
29. Patti G, Malerba F, Calevo MG, et al. Puberetal timing in children with Silver Russell syndrome compared to those born small for gestational age. Front Endocrinol (Lausanne) 2022; PMID: 36093089.
30. Vicens-Calvet E, Espadero RM, Carrascosa A, et al. Longitudinal study of the pubertal growth spurt in children born small for gestational age without postnatal catch-up growth. J Pediatr Endocrinol Metab 2002; 15: 381–388.
31. Lazar L, Pollak U, Kalter-Leibovici O, et al. Pubertal course of persistently short children born small for gestational age (SGA) compared with idiopathic short children born appropriate for gestational age (AGA). Eur J Endocrinol 2003; 149: 425–432.
32. Mauras N, Attie KM, Reiter EO, et al. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc., Cooperative Study Group. J Clin Endocrinol Metab 2000; 85: 3653–3660.
33. Lem AJ, van der Kaay DC, de Ridder MA, et al. Adult height in short children born SGA treated with growth hormone and gonadotropin releasing hormone analog: results of a randomized, dose-response GH trial. J Clin Endocrinol Metab 2012; 97: 4096–4105.
34. Juul A, Backeljauw P, Cappa M, et al. Early growth hormone initiation leads to favorable long-term growth outcome in children born small for gestational age. J Clin Endocrinol Metab 2023; 108: 1043–1052.
35. de Bruin C, Dauber A. Growth hormone therapy in the short SGA child: Does time matter? J Clin Endocrinol Metab 2023; 108: e495–e496.
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
![Issue S3](https://www.prolekare.cz/media/cache/resolve/journal_issue/media/image_pdf/c568f4732dd5cf111101dcbe80fce4cf.jpg)
2023 Issue S3
Most read in this issue
- Anorexia nervosa from an endocrinologist's point of view
- Multiple endocrine neoplasia in childhood
- Pubertal growth in children born small for gestational age (SGA) with persistent short stature (SGA-SS). Growth hormone treatment outcomes from data of the Czech countywide REPAR database
- Current view on the diagnostics of growth hormone deficiency in childhood and adolescence