title: A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.
abstract: BACKGROUND
  Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies.
  
  
  METHODS
  In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration.
  
  
  RESULTS
  The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups.
  
  
  CONCLUSIONS
  IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children.
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden rikke.beck@dadlnet.dk.
authors: Rikke Beck
authors: RB
authors: Jensen
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Ajay
authors: A
authors: Thankamony
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Susan M
authors: SM
authors: O'Connell
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Jeremy
authors: J
authors: Kirk
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Malcolm
authors: M
authors: Donaldson
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Sten-A
authors: SA
authors: Ivarsson
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Olle
authors: O
authors: Söder
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Edna
authors: E
authors: Roche
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Hilary
authors: H
authors: Hoey
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: David B
authors: DB
authors: Dunger
authors: Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Anders
authors: A
authors: Juul
mesh_terms: D000375:Aging; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D016896:Treatment Outcome
chemical_list: C583557:IGF1 protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I