Journal Article

Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study

Rosenfeld, Ron G, Quigley, Charmian A, Child, Christopher J, Zimmermann, Alan G, Robison, Leslie L, Blum, Werner F

2017

Overview

CONTEXT:Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood. OBJECTIVE:To assess mortality in children receiving GH. DESIGN:Prospective, multinational, observational study. SETTING:Eight hundred twenty-seven study sites in 30 countries. PATIENTS:Children with growth disorders. INTERVENTIONS:GH treatment during childhood. MAIN OUTCOME MEASURE:Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population. RESULTS:Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65). CONCLUSIONS:No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.

• Publisher: Copyright Oxford University Press,Oxford University Press
• Subject: Adolescent / Age / Benign / Body Height - drug effects / Child / Child mortality / Child, Preschool / Children / Cohort Studies / Confidence Intervals / Dose-Response Relationship, Drug / Drug Administration Schedule / Female / Genetic disorders / Gestational age / Growth disorders / Growth Disorders - diagnosis / Growth Disorders - drug therapy / Growth Disorders - mortality / Growth hormones / Health risk assessment / Homeobox / Human Growth Hormone - adverse effects / Human Growth Hormone - therapeutic use / Humans / Internationality / Kaplan-Meier Estimate / Male / Malignancy / Mortality / Patients / Pediatrics / Prospective Studies / Reference Values / Risk Assessment / Small for gestational age / Survival Analysis / Treatment Outcome / Turner's syndrome