LUNG RESPONSES TO ULTRASOUND-GUIDED FETAL TREATMENTS WITH CORTICOSTEROIDS IN PRETERM LAMBS

Maternal corticosteroid treatments augument lung function in the human preterm infant. However, not all fetuses respond, the response requir es greater-than-or-equal-to 48 h of exposure, and multiple maternal do ses expose the mother to potential risks. To evaluate the potential of direct fetal therapy, we used ultrasound to direct fetal intramuscula r or intravascular injections of corticosteroids or saline in sheep an d subsequently derived the preterm lambs at 128 days gestational age t o assess postnatal lung function. Relative to saline-injected controls , 0.5 or 2 mg/kg betamethasone given as a single intramuscular dose 48 h before delivery increased compliance and the efficiency of ventilat ion (as measured by an indicator that included ventilatory pressures a nd CO2 values) nearly twofold (P < 0.05). Lung volumes, measured from deflation pressure-volume curves, also increased (P < 0.05). However, the 2 mg/kg dose caused severe pulmonary interstitial emphysema in 5 o f 13 lambs, suggesting adverse effects. An intravascular fetal dose of 12.5 mg/kg hydrocortisone or an intramuscular dose of 0.1 mg/kg betam ethasone had no effect on postnatal lung function. In separate studies , the 2 mg/kg dose improved all indicators of lung function almost two fold after only 24 h of fetal exposure and delivery at 128 days gestat ional age (P < 0.01). There was a dose-dependent suppression of the po stnatal cortisol surge in treated animals, although fetal treatment di d not alter cord cortisol levels. Single-dose fetal hormone treatments can cause large and rapid improvements in postnatal lung function in preterm lambs.