Prenatal exposure to epidermal growth factor attenuates respiratory distress syndrome in rhesus infants.
Treatment of nonhuman primate fetuses with epidermal growth factor (EGF) results in histologic and biochemical maturation of their lungs. To determine whether these effects improve lung function postnatally, we studied premature rhesus infants delivered at 78% of gestation after in utero treatment with EGF (n = 5) or placebo (n = 5). Indices of lung function during the 4 d of postnatal care included fractional concentration of inspired oxygen, peak inspiratory pressure, ventilator rate, mean airway pressure, arterial to alveolar oxygen tension ratio, and ventilation index. Statistically significant differences were noted in the time courses of these variables between EGF- and placebo-treated infants. The direction of the differences indicated that the EGF-treated infants had less severe lung disease. Surfactant apoprotein A concentration and lecithin to sphingomyelin ratio were both significantly higher in the amniotic fluid of the EGF-treated group, indicating advanced biochemical maturation in this group of animals. Whereas birth weight was not affected by EGF exposure, adrenal and gut weights, standardized for body weight, were increased significantly. Histologic studies showed advanced cellular maturation with increased parenchymal airspace and decreased parenchymal tissue space in the EGF-treated group compared with the control group. We conclude that prenatal exposure to EGF stimulates biochemical and histologic maturation of the lung and markedly attenuates the clinical severity of respiratory disease in this model of simian respiratory distress syndrome.
Goetzman
B W
BW
Department of Pediatrics, School of Medicine, University of California, Davis 95616.
Read
L C
LC
Plopper
C G
CG
Tarantal
A F
AF
George-Nascimento
C
C
Merritt
T A
TA
Whitsett
J A
JA
Styne
D
D
D000653:Amniotic Fluid; D000818:Animals; D000831:Animals, Newborn; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D010529:Peritoneal Cavity; D011247:Pregnancy; D011994:Recombinant Proteins / Q000008:administration & dosage; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy
D011994:Recombinant Proteins; D004815:Epidermal Growth Factor