title: Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics.
abstract: 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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  Death.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Albertsson-Wikland
authors.affiliation: 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.
authors.forename: Anton
authors.initials: A
authors.lastname: Mårtensson
authors.affiliation: 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.
authors.forename: Lars
authors.initials: L
authors.lastname: Sävendahl
authors.affiliation: 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.
authors.forename: Aimon
authors.initials: A
authors.lastname: Niklasson
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.affiliation: 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.
authors.forename: Jovanna
authors.initials: J
authors.lastname: Dahlgren
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.affiliation: 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.
authors.forename: Berit
authors.initials: B
authors.lastname: Kriström
authors.affiliation: 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.
authors.forename: Svante
authors.initials: S
authors.lastname: Norgren
authors.affiliation: 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.
authors.forename: Nils-Gunnar
authors.initials: NG
authors.lastname: Pehrsson
authors.affiliation: 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.
authors.forename: Anders
authors.initials: A
authors.lastname: Odén
mesh_terms: D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000401:mortality*; D020249:Hormone Replacement Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D008962:Models, Theoretical; D011994:Recombinant Proteins / Q000627:therapeutic use*; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone