Kerstin Albertsson-Wikland1, Anton Mårtensson1, Lars Sävendahl1, Aimon Niklasson1, Peter Bang1, Jovanna Dahlgren1, Jan Gustafsson1, Berit Kriström1, Svante Norgren1, Nils-Gunnar Pehrsson1, Anders Odén1. 1. Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology (K.A.-W., A.M.), The Sahlgrenska Academy at University of Gothenburg, SE-405 30 Gothenburg, Sweden; Statistiska Konsultgruppen (A.M., N.-G.P., A.O.), SE-413 19 Gothenburg, Sweden; Department of Women's and Children's Health, Karolinska Institutet, and Pediatric Endocrinology Unit (L.S., S.N.), Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Gothenburg Pediatric Growth Research Center, Department of Pediatrics (A.N., J.D.), Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, SE-416 85 Gothenburg, Sweden; Department of Clinical and Experimental Medicine, Division of Pediatrics (P.B.), University of Linköping, SE- 581 85 Linköping, Sweden; Department of Women's and Children's Health (J.G.), Uppsala University, SE-751 85 Uppsala, Sweden; Department of Clinical Science, Pediatrics (B.K.), Umeå University, SE- 901 85 Umeå, Sweden; and Department of Mathematical Sciences (A.O.), Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
Abstract
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 (ISS) 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.
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 (ISS) 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.
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