Abstract 1186 Neonatal Disease Oriented Research: Ductus and Surfactant Platform, Sunday, 5/2

Background: Clinical amnionitis and the experimental intra-amniotic injection of the proinflammatory cytokine IL-1 were previously shown to be associated with a decrease in RDS and early fetal lung maturation, respectively. Hypothesis: The potent proinflammatory stimulus resulting from endotoxin will stimulate fetal lung maturation. Methods: Ewes with singleton fetuses at 119d gestational age (GA) were randomized to receive 20 mg E coli 055:B5 endotoxin (N=10) or saline (N=5) by ultrasound guided intraamniotic injection. Comparison ewes were randomized to 0.5 mg/kg betamethasone (Beta) maternal 1M (N=10) or saline (N=9) at 118d GA. All lambs were delivered at 125d GA and ventilated for 40 min to assess lung function (compliance, ml/cmH2O/kg). Maximal lung gas volume (ml/kg) was measured with 40 cmH2O pressure (V 40), and an alveolar wash (AW) was recovered to measure surfactant saturated phosphatidylcholine (Sat PC, µmol/kg), SP-B (relative to control value) and total protein (mg/kg). Results: The two control groups were not different and were combined for all comparisons. Fetal exposure to intraamniotic endotoxin improved postnatal lung compliance by 59% and increased lung gas volume 2.3 fold (Table). The endotoxin exposure also increased Sat PC 9.5 fold and SP-B 8.8 fold in AW. Although white blood cells increased in endotoxin exposed fetuses (by scoring of lung sections, p<0.01), severe inflammation was not evident and total protein was decreased in AW of endotoxin exposed preterm lambs. Maternal Beta treatment was in general less effective as a maturational stimulus as evaluated by improved lung function or surfactant indicators. Conclusions: Fetal exposure to a single intraamniotic endotoxin dose improved lung function and increased alveolar Sat PC and SP-B after a 6 day treatment to delivery interval. The effects exceeded those achieved with maternal Beta. Speculation: An understanding of the endotoxin response will provide new insights into modulators of fetal lung maturation.

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Funded by HD-12714 from NIH-NICHD and Women and Infants Research Foundation, Perth, Australia.