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

N1 - © 2014 European Society of Endocrinology.

PY - 2014

Y1 - 2014

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 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.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 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.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

VL - 171

SP - 509

EP - 518

JO - Acta Endocrinologica, Supplement

JF - Acta Endocrinologica, Supplement

SN - 0804-4635

IS - 4

ER -