Factors influencing height gain in children born small for gestational age treated with recombinant growth hormone: what extent is puberty involved?

Abstract

Objective: The objective was to analyze the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) without catch-up growth treated before the onset of puberty, with follow-up until adult height. The influence of demographic and auxological factors on the final response evaluated as adult height and height gain was assessed. Patients and methods: A prospective longitudinal observational study performed in a tertiary hospital, involving SGA patients, who started treatment with rhGH between October 2003 and April 2015. Potential response predictors were evaluated by multiple regression analysis and receiver operating characteristic curves. Results: Of the initial 96 patients included, 61 patients (28 boys and 33 girls) reached adult height. Adult height gain in standard deviation (SDS) was 0.99 (0.8) and 1.49 (0.94), respectively ( p < 0.05). An adult height greater than −2 SDS was reached in 75% of the girls but only in 53% of the boys. The pubertal height gain was 22.6 (5.8) cm in boys and 18.8 (4.5) cm in girls. The multiple regression model obtained for total height gain explained 42% of the variability in this variable including sex, height gain during the first year, and the difference from target height at the start of treatment. A first-year height gain of 0.69 SDS was the optimal point for assessing a final height gain greater than 1.5 SDS with a specificity of 70% and a sensitivity of 71%. Conclusion: Most SGA patients achieve normalization of height above −2 SD, the percentage being higher in girls. According to our predictive model, height gain in the first year is the most important variable for predicting good response to treatment. During puberty, there is a loss of height SDS, probably due to a lower total pubertal gain with respect to the reference population, which is more marked in boys.

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

“…Podle většiny studií puberta u celé skupiny dětí SGA-SS začíná v obvyklém věkovém rozmezí, i když poměrně časně vzhledem k aktuální tělesné výšce. (23)(24)(25)(26)(27) Metaanalýza Denga se spolupracovníky ale ukázala, že nástup puberty je zejména u dívek přece jen časnější, než je průměr ostatních dětí. (28) Puberta nastává jednoznačně časně u obou podskupin dětí se syndromem Silvera-Russella -zejména u nositelů maternální uniparentální disomie na 7. chromozomu (mUPD7), ale také u dětí se ztrátou metylace v oblasti 11p15 (11p15 LOM).…”

Adult height in children born small for gestational age (SGA) with persistent short stature (SGA-SS). Growth hormone treatment outcomes from data of the Czech countrywide REPAR database

“…Adler et al (17) 132 (jen růstový hormon) 120 (růstový hormon + GnRHa) 65 65 0,8 0,8 Ruiz et al (16) 28 a indikované. (16,17,21,(23)(24)(25)(26)(27)(28)(29) Přesto předchozí analýzy dokázaly vysvětlit jen menší část individuální variability odpovědi na léčbu. Skupina dětí SGA-SS je etiopatogeneticky různorodá.…”

“…Díky tomu lze posoudit početné kohorty dětí, které dostávaly růstový hormon v běžném režimu, ukončily růst a dosáhly dospělé finální výšky. (16,17) Právě v tomto novém kontextu se ukazuje, že přes celkový příznivý efekt existuje v odpovědi na léčbu významná interindividuální variabilita. Nepochybně souvisí s různorodou etiologií stavu SGA-SS.…”