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

Rikke Beck Jensen; Ajay Thankamony; Susan M O'Connell; Jeremy Kirk; Malcolm Donaldson; Sten-A Ivarsson; Olle Söder; Edna Roche; Hilary Hoey; David B Dunger; Anders Juul

doi:10.1530/eje-14-0419

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

Rikke Beck Jensen, Ajay Thankamony, Susan M O'Connell, Jeremy Kirk, Malcolm Donaldson, Sten-A Ivarsson, Olle Söder, Edna Roche, Hilary Hoey, David B Dunger, Anders Juul

Institut for Klinisk Medicin

12 Citationer (Scopus)

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 mg/kg per day) to three different regimens: high dose (67 mg/kg per day), low dose (35 mg/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 mg/kg per day, S.D. 0.019) and the low-dose group (35 mg/kg per day, S.D. 0.002; PZ0.46), but there was a wide variation in the IGF1 titration group (range 10-80 mg/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; PZ0.17). 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.

Conclusion: 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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Endocrinology. Supplement
Vol/bind	171
Udgave nummer	4
Sider (fra-til)	509-518
Antal sider	10
ISSN	0804-4635
DOI	https://doi.org/10.1530/eje-14-0419
Status	Udgivet - 1 okt. 2014

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10.1530/eje-14-0419

https://eje.bioscientifica.com/downloadpdf/journals/eje/171/4/509.pdf

Citationsformater

Jensen, R. B., Thankamony, A., O'Connell, S. M., Kirk, J., Donaldson, M., Ivarsson, S-A., Söder, O., Roche, E., Hoey, H., Dunger, D. B., & Juul, A. (2014). 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. European Journal of Endocrinology. Supplement, 171(4), 509-518. https://doi.org/10.1530/eje-14-0419

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. / Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M et al.

I: European Journal of Endocrinology. Supplement, Bind 171, Nr. 4, 01.10.2014, s. 509-518.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Jensen, RB, Thankamony, A, O'Connell, SM, Kirk, J, Donaldson, M, Ivarsson, S-A, Söder, O, Roche, E, Hoey, H, Dunger, DB & Juul, A 2014, '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', European Journal of Endocrinology. Supplement, bind 171, nr. 4, s. 509-518. https://doi.org/10.1530/eje-14-0419

Jensen RB, Thankamony A, O'Connell SM, Kirk J, Donaldson M, Ivarsson S-A et al. 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. European Journal of Endocrinology. Supplement. 2014 okt. 1;171(4):509-518. doi: 10.1530/eje-14-0419

@article{38149f588ec4492398eb56a45ae6a102,

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 mg/kg per day) to three different regimens: high dose (67 mg/kg per day), low dose (35 mg/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 mg/kg per day, S.D. 0.019) and the low-dose group (35 mg/kg per day, S.D. 0.002; PZ0.46), but there was a wide variation in the IGF1 titration group (range 10-80 mg/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; PZ0.17). 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.Conclusion: 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.",

keywords = "Aging, Body Height, Child, Child, Preschool, Dose-Response Relationship, Drug, Drug Administration Schedule, Europe, Female, Human Growth Hormone, Humans, Infant, Infant, Newborn, Infant, Small for Gestational Age, Insulin-Like Growth Factor I, Male, Treatment Outcome",

author = "Jensen, {Rikke Beck} and Ajay Thankamony and O'Connell, {Susan M} and Jeremy Kirk and Malcolm Donaldson and Sten-A Ivarsson and Olle S{\"o}der and Edna Roche and Hilary Hoey and Dunger, {David B} and Anders Juul",

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TY - JOUR

T1 - A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age

T2 - the North European Small-for-Gestational-Age Study

AU - Jensen, Rikke Beck

AU - Thankamony, Ajay

AU - O'Connell, Susan M

AU - Kirk, Jeremy

AU - Donaldson, Malcolm

AU - Ivarsson, Sten-A

AU - Söder, Olle

AU - Roche, Edna

AU - Hoey, Hilary

AU - Dunger, David B

AU - Juul, Anders

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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 mg/kg per day) to three different regimens: high dose (67 mg/kg per day), low dose (35 mg/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 mg/kg per day, S.D. 0.019) and the low-dose group (35 mg/kg per day, S.D. 0.002; PZ0.46), but there was a wide variation in the IGF1 titration group (range 10-80 mg/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; PZ0.17). 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.Conclusion: 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.

AB - 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 mg/kg per day) to three different regimens: high dose (67 mg/kg per day), low dose (35 mg/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 mg/kg per day, S.D. 0.019) and the low-dose group (35 mg/kg per day, S.D. 0.002; PZ0.46), but there was a wide variation in the IGF1 titration group (range 10-80 mg/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; PZ0.17). 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.Conclusion: 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.

KW - Aging

KW - Body Height

KW - Child

KW - Child, Preschool

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Europe

KW - Female

KW - Human Growth Hormone

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Infant, Small for Gestational Age

KW - Insulin-Like Growth Factor I

KW - Male

KW - Treatment Outcome

U2 - 10.1530/eje-14-0419

DO - 10.1530/eje-14-0419

M3 - Journal article

C2 - 25080293

SN - 0804-4635

VL - 171

SP - 509

EP - 518

JO - Acta Endocrinologica, Supplement

JF - Acta Endocrinologica, Supplement

IS - 4

ER -

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

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