title: Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.
abstract: BACKGROUND
  Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects.
  
  
  OBJECTIVE
  The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.
  
  
  METHODS
  We conducted a multicenter prospective trial.
  
  
  METHODS
  Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)).
  
  
  RESULTS
  Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids.
  
  
  CONCLUSIONS
  Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.
authors.affiliation: Clinical Research Fellow, Dutch Growth Research Foundation, Erasmus University Medical Center/Sophia Children's Hospital, Westzeedijk 106, 3016 AH Rotterdam, The Netherlands. r.delindvanwijngaarden@erasmusmc.nl
authors.forename: Roderick F A
authors.initials: RF
authors.lastname: de Lind van Wijngaarden
authors.forename: Elbrich P C
authors.initials: EP
authors.lastname: Siemensma
authors.forename: Dederieke A M
authors.initials: DA
authors.lastname: Festen
authors.forename: Barto J
authors.initials: BJ
authors.lastname: Otten
authors.forename: Edgar G A H
authors.initials: EG
authors.lastname: van Mil
authors.forename: Joost
authors.initials: J
authors.lastname: Rotteveel
authors.forename: Roelof J H
authors.initials: RJ
authors.lastname: Odink
authors.forename: G C B Karen
authors.initials: GC
authors.lastname: Bindels-de Heus
authors.forename: Mariëtte
authors.initials: M
authors.lastname: van Leeuwen
authors.forename: Danny A J P
authors.initials: DA
authors.lastname: Haring
authors.forename: Gianni
authors.initials: G
authors.lastname: Bocca
authors.forename: E C A Mieke
authors.initials: EC
authors.lastname: Houdijk
authors.forename: J J Gera
authors.initials: JJ
authors.lastname: Hoorweg-Nijman
authors.forename: René C F M
authors.initials: RC
authors.lastname: Vreuls
authors.forename: Petr E
authors.initials: PE
authors.lastname: Jira
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Bakker
authors.forename: Eelco J
authors.initials: EJ
authors.lastname: Schroor
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Pilon
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D001724:Birth Weight; D001794:Blood Pressure; D001827:Body Height; D001835:Body Weight; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005215:Fasting; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000188:drug therapy*; D011446:Prospective Studies; D012449:Safety
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I