Prediction of Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age: Analysis of Data from KIGS (Pharmacia International Growth Database)

Abstract

A model was developed that allows physicians to individualize GH treatment in children born short for gestational age (SGA) who fail to show spontaneous catch-up growth. Data from children (n = 613) in a large pharmacoepidemiological survey, the KIGS (Pharmacia International Growth Database), or who had participated in clinical trials were used to develop the model. Another group of similar children (n = 68) from KIGS was used for validation. In the first year of GH treatment, the growth response correlated positively with GH dose, weight at the start of GH treatment, and midparental height SD score and negatively with age at treatment start. Using this model, 52% of the variability of the growth response could be explained, with a mean error SD of 1.3 cm. GH dose was the most important response predictor (35% of variability), followed by age at treatment start. The second year growth response was best predicted by a three-parameter model (height velocity in yr 1 of treatment, age at start of treatment, and GH dose), which accounted for 34% of the variability, with an error SD of 1.1 cm. The first year response to GH treatment was the most important predictor of the second year response, accounting for 29% of the variability. No statistically significant differences between the predicted and observed growth responses were found when the models were applied to the validation groups. In conclusion, using simple variables, we have developed a model that can be used in clinical practice to adjust the GH dose to achieve the desired growth response in patients born SGA. Furthermore, this model can be used to provide patients with a realistic expectation of treatment and may help to identify compliance problems or other underlying causes of treatment failure.

Preditores clínicos do ganho estatural do primeiro ano de tratamento com dose fixa de hormônio de crescimento em crianças nascidas pequenas para idade gestacional

“…A idade óssea no início do tratamento, em acordo com a literatura (7,20), foi identificada como uma das variáveis preditoras do ganho estatural no primeiro ano de tratamento, ressaltando a correlação negativa com o ganho estatural (21).…”

“…Apesar de alguns estudos demonstrarem relação direta entre dose e resposta ao tratamento nas crianças nascidas PIG (7,8,14,15), nosso estudo mostrou que a dose fixa de 1,0 UI/kg/semana (0,33 mg/kg/semana) foi capaz de promover um catch up de crescimento rele-Arq Bras Endocrinol Metab. 2010;54/5…”

“…As principais variáveis reconhecidas como preditoras do crescimento do primeiro ano de tratamento são a dose do hormônio utilizada, a idade de início do tratamento, o Z-escore de peso pré-tratamento e o canal familiar (7,8). Contudo, essas variáveis não são capazes de explicar por completo a variabilidade observada no ganho estatural.…”

Characterization and prevalence of severe primary IGF1 deficiency in a large cohort of French children with short stature

“…on the ISS curve according to gender (20) or height velocity between 7 and 11.4 cm (10th-90th percentiles) for SGA children (21)); and ii) good height response (defined as height gain O0.5 S.D.) (22); plus iii) (if available) normalization of IGF1 levels to the normal range for chronological age and pubertal stage.…”

Growth hormone treatment in children born small for gestational age: One center experience

“…The International Societies of Pediatric Endocrinology and the Growth Hormone Research Society consensus statement proposes that children born SGA with height below −2.5 SDs at age 2, or with height below −2 SDs at age 4, should be treated with growth hormone (5). It is well known that one of the major factors for a good response to growth hormone therapy is lower age, so it is suggested that all short SGA children older than four years are candidates for growth hormone therapy (6,10).…”