Beneficial Effects of Growth Hormone Treatment on Cognition in Children with Prader-Willi Syndrome: A Randomized Controlled Trial and Longitudinal Study

Author:

Siemensma Elbrich P. C.1,Tummers-de Lind van Wijngaarden Roderick F. A.12,Festen Dederieke A. M.12,Troeman Zyrhea C. E.1,van Alfen-van der Velden A. A. E. M. (Janielle)3,Otten Barto J.3,Rotteveel Joost4,Odink Roelof J. H.5,Bindels-de Heus G. C. B. (Karen)2,van Leeuwen Mariette6,Haring Danny A. J. P.7,Oostdijk Wilma8,Bocca Gianni9,Mieke Houdijk E. C. A.10,van Trotsenburg A. S. Paul11,Hoorweg-Nijman J. J. Gera12,van Wieringen Hester12,Vreuls René C. F. M.13,Jira Petr E.14,Schroor Eelco J.15,van Pinxteren-Nagler Evelyn16,Willem Pilon Jan17,Lunshof L. (Bert)18,Hokken-Koelega Anita C. S.1

Affiliation:

1. Dutch Growth Research Foundation (E.P.C.S., R.F.A.T.-d.L.v.W., D.A.M.F., Z.C.E.T., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands

2. Departments of Pediatric Endocrinology, Erasmus University Medical Center Rotterdam/Sophia Children's Hospital (E.P.C.S., R.F.A.T.-d.L.v.W., D.A.M.F., G.C.B.B.-d.H., A.C.S.H.-K.), 3015 GJ Rotterdam, The Netherlands

3. Radboud University Nijmegen Medical Center (A.A.E.M.v.A.-v.d.V., B.J.O.), 6500 HB Nijmegen, The Netherlands

4. VU University Medical Center (J.R.), 1081 HV Amsterdam, The Netherlands

5. St. Catharina Hospital (R.J.H.O.), 5623 EJ Eindhoven, The Netherlands

6. St. Jansdal Hospital (M.v.L.), 3844 DG Harderwijk, The Netherlands

7. Diaconessen Hospital (D.A.J.P.H.), 2334 CK Leiden, The Netherlands

8. Leiden University Medical Center (W.O.), 2333 ZA Leiden, The Netherlands

9. University Medical Center Groningen/Beatrix Children's Hospital (G.B.), 9713 GZ Groningen, The Netherlands

10. Haga Hospitals/Juliana Children's Hospital (E.C.A.M.H.), 2566 MJ The Hague, The Netherlands

11. Academic Medical Center, University of Amsterdam (A.S.P.v.T.), 1105 AZ Amsterdam, The Netherlands

12. St. Antonius Hospital (J.J.G.H.-N., H.v.W.), 3430 EM Nieuwegein, The Netherlands

13. Medical Center Twente (R.C.F.M.V.), 7511 JX Enschede, The Netherlands

14. Department of Pediatrics, Jeroen Bosch Hospital (P.E.J.), 5200 ME 's-Hertogenbosch, The Netherlands

15. Isala Hospitals (E.J.S.), 8025 AB Zwolle, The Netherlands

16. Medical Center Leeuwarden (E.v.P.-N.), 8901 BR Leeuwarden, The Netherlands

17. IJsselmeer Hospitals (J.W.P.), 8233 AA Lelystad, The Netherlands

18. Gelre Hospitals (L.L.), 7300 SD Apeldoorn, The Netherlands

Abstract

AbstractBackground:Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited.Methods:Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr of GH treatment. Cognitive functioning was measured biennially by short forms of the WPPSI-R or WISC-R, depending on age. Total IQ (TIQ) score was estimated based on two subtest scores.Results:During the randomized controlled trial, mean sd scores of all subtests and mean TIQ score remained similar compared to baseline in GH-treated children with PWS, whereas in untreated controls mean subtest sd scores and mean TIQ score decreased and became lower compared to baseline. This decline was significant for the Similarities (P = 0.04) and Vocabulary (P = 0.03) subtests. After 4 yr of GH treatment, mean sd scores on the Similarities and Block design subtests were significantly higher than at baseline (P = 0.01 and P = 0.03, respectively), and scores on Vocabulary and TIQ remained similar compared to baseline. At baseline, children with a maternal uniparental disomy had a significantly lower score on the Block design subtest (P = 0.01) but a larger increment on this subtest during 4 yr of GH treatment than children with a deletion. Lower baseline scores correlated significantly with higher increases in Similarities (P = 0.04) and Block design (P < 0.0001) sd scores.Conclusions:Our study shows that GH treatment prevents deterioration of certain cognitive skills in children with PWS on the short term and significantly improves abstract reasoning and visuospatial skills during 4 yr of GH treatment. Furthermore, children with a greater deficit had more benefit from GH treatment.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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