Peak bone mass after exposure to antenatal betamethasone and prematurity: follow-up of a randomized controlled trial.
Small birth size is associated with reduced adult bone mass. We determined if antenatal betamethasone exposure, birth weight, or prematurity affects peak bone mass in 174 adults. Antenatal betamethasone exposure did not. Lower birth weight and prematurity predicted reduced adult height. Slower fetal growth rather than prematurity predicted lower bone mass, but this lower bone mass was appropriate for reduced adult height.


BACKGROUND
Small size at birth is reported to be associated with lower bone mass in adulthood. However, previous studies have not distinguished the relative contributions of length of gestation and fetal growth to size at birth. Fetal exposure to excess glucocorticoids has been proposed as a core mechanism underlying the associations between birth size and later disease risk. Antenatal glucocorticoids are given to pregnant women at risk for preterm delivery for the prevention of neonatal respiratory distress syndrome in their infants. We determined the relationship of antenatal exposure to betamethasone, birth weight, and prematurity to peak bone mass and femoral geometry in the adult survivors of the first randomized trial of antenatal glucocorticoids.


METHODS
We studied 174 young adults (mean age, 31 years) whose mothers participated in a randomized trial of antenatal betamethasone. Mothers received two doses of intramuscular betamethasone or placebo 24 h apart. Two thirds of participants were born preterm (<37 weeks gestation). We measured indices of bone mass and size and derived estimates of volumetric density and bone geometry from DXA assessments of the lumbar spine, femur, and total body.


RESULTS
There were no differences between betamethasone-exposed and placebo-exposed groups in any of the lumbar spine, femur, or total body DXA measures. There was no effect of antenatal betamethasone on adult height, although leg length was increased relative to trunk length (p = 0.002). A lighter birth weight (p <or = 0.001) and lower gestational age (p = 0.013) were associated with shorter stature (height Z scores) at age 31 years. Prematurity had no effect on peak bone mass or femoral geometry. However, lower birth weight, independent of gestational age, was associated with lower later bone mass (p < 0.001 for lumbar spine and total body, p = 0.003 for femoral neck BMC). These effects on bone mass were related to bone size and not to estimates of volumetric density. In the femur, lower birth weight, independent of gestational age, was associated with narrowing of the upper shaft and narrow neck regions.


CONCLUSIONS
Antenatal betamethasone exposure does not affect peak bone mass or femoral geometry in adulthood. Birth weight and prematurity predict adult height, but it is slower fetal growth, rather than prematurity, that predicts lower peak bone mass. The lower peak bone mass in those born small is appropriate for their adult height.
Dalziel
Stuart R
SR
Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand.
Fenwick
Sheryl
S
Cundy
Tim
T
Parag
Varsha
V
Beck
Thomas J
TJ
Rodgers
Anthony
A
Harding
Jane E
JE
D015502:Absorptiometry, Photon; D001623:Betamethasone / Q000008:administration & dosage*; D001724:Birth Weight; D001827:Body Height; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000293:injuries; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D047928:Premature Birth; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D012127:Respiratory Distress Syndrome, Newborn / Q000517:prevention & control
D001623:Betamethasone