Mortality is not increased in rhGH-treated patients when adjusting for birth characteristics.
Journal article, 2016

Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

Author

Kerstin Albertsson-Wikland

University of Gothenburg

Anton Mårtensson

University of Gothenburg

Lars Sävendahl

Karolinska University Hospital

Aimon Niklasson

University of Gothenburg

Peter Bang

Linköping University

Jovanna Dahlgren

University of Gothenburg

Jan Gustafsson

Uppsala University

Berit Kriström

Umeå University

Svante Norgren

Karolinska University Hospital

Nils-Gunnar Pehrsson

Statistiska Konsultgruppen

Anders Odén

Chalmers, Mathematical Sciences, Mathematical Statistics

University of Gothenburg

The Journal of clinical endocrinology and metabolism

1945-7197 (eISSN)

Vol. 101 5 2149-2159

Subject Categories

Pediatrics

DOI

10.1210/jc.2015-3951

PubMed

26918292

More information

Latest update

2/28/2018