Betamethasone in the last week of pregnancy causes fetal growth retardation but not adult hypertension in rats.
We tested the hypotheses that (1) maternal betamethasone (betaM) treatment over the range of clinical doses for prevention of prematurity-related pathologies from day 15 to 21 of rat gestation would produce growth retardation, and (2) the lowest betaM dose to produce growth retardation would result in hypertension in adult offspring. In experiment 1, pregnant Sprague-Dawley rats were administered betaM (0, 50, 100, 200, 400, or 600 microg/kg per day, subcutaneously) on days 15-21 of pregnancy and necropsied on day 21.5, with fetal lung and placental weights recorded. In experiment 2, two more groups of rats (0 or 100 microg/kg per day, subcutaneously) were allowed to deliver, and offspring were instrumented at 100 +/- 4 days of postnatal life with indwelling left carotid arterial catheters. After 48 hours of recovery, blood pressure was recorded continuously for 24 hours. In experiment 1, all newborn rats treated with betaM, and their placentas, except those receiving 50 microg/kg per day, were growth retarded in comparison with controls (P <.05). All treated lungs were smaller than those of controls (P <.05). In experiment 2, no differences were found in the mean arterial blood pressure of adult offspring given the lowest effective dose of betaM (100 microg/kg per day) compared with controls (114.2 +/- 5.3 mmHg versus 114.6 +/- 3.4 mmHg, respectively). These data suggest that glucocorticoids given in the last week of rat pregnancy in the lowest human clinical dose do not cause hypertension and somatic growth retardation. However, the presence of lung growth restriction at this dose argues for more studies on the efficacy of even lower concentrations for their ability to improve lung and other organ and tissue function while avoiding unwanted side effects.
McDonald
T J
TJ
Laboratory for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY 10012, USA. tmcdonal@sfbr.org
Franko
K L
KL
Brown
J M
JM
Jenkins
S L
SL
Nathanielsz
P W
PW
Nijland
M J
MJ
D000818:Animals; D001623:Betamethasone / Q000009:adverse effects*; D001724:Birth Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001623:Betamethasone