Fetal growth velocity, size in early life and adolescence, and prediction of bone mass: association to the GH-IGF axis.
Poor growth in early life is associated with numerous adverse outcomes later in life. In 123 adolescents 16-18 yr of age, the previous findings of a positive relation between size in early life and later bone mass was confirmed. These associations were mediated by the current height and weight, but it was not confirmed that alterations of the GH-IGF axis cause this.


BACKGROUND
Numerous studies have found associations between low birth weight and disease later in life, including decreased bone mass.


METHODS
A longitudinal cohort of 16- to 19-year-old adolescents (n = 123) with data on third trimester fetal growth velocity (FGV) was assessed by serial ultrasound measurements, birth weight (BW), and weight at 1 yr. A follow-up study included DXA scan, anthropometric measurements, and measurements of the growth hormone (GH) -IGF-I axis in a representative subpopulation (n = 30).


RESULTS
BW and weight at 1 yr were positively associated with whole body BMC (p = 0.02 and p < 0.0001, respectively), lumbar spine BMC (p = 0.001 and p = 0.03, respectively), and lumbar spine BMD (p = 0.04). After correction for adolescent height and weight, no association remained significant. There was no relation between IGF-I and IGF binding protein 3 (IGFBP-3) levels in adolescence and size in early life or bone mass. In the subpopulation, GH secretion (median, 2.58 versus 4.05), GH pulse mass (median, 10.7 versus 19.4 mU/liter), and total GH (median, 74.9 versus 108.8 mU/liter/12 h) were decreased in the small for gestational age (SGA) group compared with the appropriate for gestational age (AGA) group; this did not reach statistical significance. Likewise, there were no differences in IGF-I, IGF-II, and IGFBP-1, -2, and -3 levels between the SGA and AGA groups. A statistically significant positive association between FGV and adolescent IGF-II was found (B = 199.9, p = 0.006). Significant negative associations between GH measurement and BMC, as well as BMD, were found (B = -0.008, p = 0.005 and B = -0.008, p = 0.006, respectively).


CONCLUSIONS
This study confirms the previous findings of a positive relation between size in early life and later BMC, an association apparently independent of the distal part of the GH/IGF-I axis. However, this association may be mediated mainly by postnatal growth determining size of the skeletal envelope rather than an effect of fetal programming on bone mass per se.
Jensen
Rikke Beck
RB
University Department of Growth and Reproduction Rigshospitalet, Copenhagen, Denmark. rikke.beck@rh.hosp.dk
Vielwerth
Signe
S
Frystyk
Jan
J
Veldhuis
Johannes
J
Larsen
Torben
T
Mølgaard
Christian
C
Greisen
Gorm
G
Juul
Anders
A
D000293:Adolescent; D041923:Adolescent Development; D000328:Adult; D001724:Birth Weight; D015519:Bone Density; D001846:Bone Development; D005260:Female; D047109:Fetal Development; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000097:blood / Q000209:etiology; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007223:Infant; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D011247:Pregnancy; D011263:Pregnancy Trimester, Third
D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II