Abstract
Transition of growth from infancy to childhood is associated with activation of the GH-IGF-I axis. Children with a delayed infancy-childhood transition (DICT) are short as adults. Thus, age at ICT may impact on growth response to GH. The objective was to investigate associations between growth response to GH treatment and ICT timing in children with idiopathic short stature (ISS) in a randomized, controlled, multicenter trial, TRN 88-080. A total of 147 prepubertal children (mean age, 11.5 ± 1.4 y) were randomized to receive GH 33 μg/kg/d (GH33, n = 43), GH 67 μg/kg/d (GH67, n = 61), or no treatment (n = 43). Data on growth to final height (FH) were analyzed after categorization into those with normal (n = 76) or delayed ICT (n = 71). Within the GH33 group, significant height gain at FH was only observed in children with a DICT (p < 0.001), with each month of delay corresponding to gain of 0.13 SD score (SDS). For the GH67 group, the timing of the onset of the ICT had no impact on growth response. In conclusion, ISS children with a DICT responded to standard GH dose (better responsiveness), whereas those with a normal ICT required higher doses to attain a significant height gain to FH.
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Abbreviations
- AGA:
-
appropriate for GA
- AITT:
-
arginine-insulin tolerance test
- DICT:
-
delayed infancy-childhood transition
- diffMPHSDS:
-
difference in child heightSDS versus midparental height (MPH)SDS
- FH:
-
final height
- GH33:
-
GH dose 33 μg/kg/d
- GH67:
-
GH dose 67 μg/kg/d
- GHD:
-
growth hormone deficiency
- GHmax:
-
maximum peak of GH
- ICP:
-
infancy-childhood-puberty
- ICT:
-
infancy-childhood-transition
- ISS:
-
idiopathic short stature
- IGFBP3:
-
insulin-like growth-factor-I-binding protein 3
- ITT:
-
intention-to-treat
- MPH:
-
midparental height
- non-DICT:
-
normal infancy-childhood-transition
- PP:
-
per-protocol
- SDS:
-
standard deviation score
- SGA:
-
small for GA
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Acknowledgements
We thank the study group for allowing us to use the data for this analysis. The study group included Kerstin Albertsson-Wikland, A. Stefan Aronson, Jan Gustafsson, Lars Hagenäs, Sten A. Ivarsson, Berit Kriström, Claude Marcus, Karl Olof Nilsson, E. Martin Ritzén, Torsten Tuvemo, Otto Westphal, and Jan Åman.
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This study TR 88-080 was initiated in 1988 as a Kabi-sponsored study and changed to an Investigator-sponsored study in the 1990s. The study was supported by grants from Swedish Research Council (7509) and Foundation Växthuset for Children.
An unrestricted research grant and free drug was kindly provided by Pharmacia/Pfizer. B.J. and B.K. have received a consultancy fee from Pfizer. Pfizer had no influence on collection, analyses, and interpretation of data or in writing of this manuscript.
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Albertsson-Wikland, K., Kriström, B., Jonsson, B. et al. Long-Term Response to GH Therapy in Short Children With a Delayed Infancy-Childhood Transition (DICT). Pediatr Res 69, 504–510 (2011). https://doi.org/10.1203/PDR.0b013e3182139243
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DOI: https://doi.org/10.1203/PDR.0b013e3182139243
