Adult height in short children born SGA treated with growth hormone and gonadotropin releasing hormone analog: results of a randomized, dose-response GH trial.
BACKGROUND
GH treatment is effective in improving height in short children born small for gestational age (SGA). GH is thought to have limited effect when started during adolescence.


OBJECTIVE
The aim of this study was to investigate GH treatment efficacy in short SGA children when treatment was started during adolescence; to assess whether GH 2 mg/m(2) · d during puberty improves adult height (AH) compared with 1 mg/m(2) · d; and to assess whether an additional 2-yr postponement of puberty by GnRH analog (GnRHa) improves AH in children who are short at the start of puberty (<140 cm), with a poor AH expectation.


METHODS
In this longitudinal, randomized, dose-response GH trial, we included 121 short SGA children (60 boys) at least 8 yr of age. We performed intention-to-treat analyses on all children and uncensored case analyses on 84 children who reached AH. Besides, we evaluated growth during 2 yr of combined GH/GnRHa and subsequent GH treatment until AH in a subgroup of 40 pubertal children with a height of less than 140 cm at the start.


RESULTS
Short SGA children started treatment at a median age of 11.2 yr, when 46% had already started puberty. Median height increased from -2.9 at start to -1.7 sd score (SDS) at AH (P < 0.001). Treatment with GH 2 vs. 1 mg/m(2) · d during puberty resulted in significantly better AH (P = 0.001), also after correction for gender, age at start, height SDS at start, treatment years before puberty, and target height SDS. AH was similar in children who started puberty at less than 140 cm and received GH/GnRHa, compared with children who started puberty greater than 140 cm and received GH only (P = 0.795).


CONCLUSIONS
When started in adolescence, GH treatment significantly improves AH in short SGA children, particularly with GH 2 mg/m(2) · d during puberty. When SGA children are short at the start of puberty, they can benefit from combined GH/GnRHa treatment.
Dutch Growth Research Foundation, P.O. Box 23068, 3001 KB Rotterdam, The Netherlands. a.lem@kindengroei.nl
Annemieke J
AJ
Lem
Danielle C M
DC
van der Kaay
Maria A J
MA
de Ridder
Willie M
WM
Bakker-van Waarde
Flip J P C M
FJ
van der Hulst
Jaap C
JC
Mulder
Cees
C
Noordam
Roel J
RJ
Odink
Wilma
W
Oostdijk
Eelco J
EJ
Schroor
Eric J
EJ
Sulkers
Ciska
C
Westerlaken
Anita C S
AC
Hokken-Koelega
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000187:drug effects* / Q000502:physiology; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D008137:Longitudinal Studies; D008297:Male; D016896:Treatment Outcome
D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone