Dose-response effects of betamethasone on maturation of the fetal sheep lung.
OBJECTIVE
Glucocorticoid administration to women in preterm labor improves neonatal mortality and morbidity. Fetal exposure to glucocorticoid levels higher than those appropriate to the current gestational stage has multiple organ system effects. Some, eg, fetal hypertension, are maximal at lower than the clinical dose. We hypothesized that the clinical dose has supramaximal lung maturational effects.


METHODS
We evaluated the full, half, and quarter clinical betamethasone dose (12 mg/70 kg or 170 microg/kg intramuscularly twice 24 hours apart) on fetal sheep lung pressure volume curves (PVC) after 48 hours' exposure at 0.75 gestation. We measured key messenger RNAs and protein products that affect lung function and total lung dipalmitoyl phosphatidyl choline.


RESULTS
Full and half doses had similar PVC and total lung dipalmitoyl phosphatidyl choline effects. Messenger RNA for surfactant proteins A, B, and D and elastin increased in a dose-dependent fashion.


CONCLUSIONS
Half the clinical betamethasone dose produces maximal PVC improvement in fetal sheep at 0.75 gestation.
Loehle
Matthias
M
Department of Neurology, University of Jena, Jena, Germany.
Schwab
Matthias
M
Kadner
Susan
S
Maner
Kristal M
KM
Gilbert
Jeffrey S
JS
Brenna
J Thomas
JT
Ford
Stephen P
SP
Nathanielsz
Peter W
PW
Nijland
Mark J
MJ
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000032:analysis; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects*; D020567:Fetal Weight / Q000187:drug effects; D008168:Lung / Q000196:embryology*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep
D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D015060:1,2-Dipalmitoylphosphatidylcholine; D001623:Betamethasone