The Extrauterine Environment for Neonatal Development Supports Mid-Gestation Fetal Lambs

Abstract

INTRODUCTION: Extreme prematurity remains the leading cause of morbidity and mortality in pediatrics. The Extrauterine Environment for Neonatal Development (EXTEND) has previously been reported to sustain lambs at >105 days gestational age (GA), which is equivalent for lung development to a 23- to 24-week human fetus, for up to 28 days. However, to assess the risk for intraventricular hemorrhage on EXTEND, an earlier gestation model is required. The 85- to 95-day GA lamb has brain development and size equivalence to the 23- to 24-week human fetus. Previous studies at this age were limited by an inability to sustain animals for >7 days due to physiologic derangements. METHODS: Fetal lambs between 90 and 95 days GA underwent umbilical vascular cannulation onto a pumpless membrane oxygenator circuit and were delivered into a closed, fluid environment with continuous “amniotic” fluid exchange. Lambs were monitored for circuit blood flow, heart rate, and oxygenation, with more aggressive flow, hematocrit, and nutrition management than in the previous 85- to 95-day GA studies. RESULTS: Of 23 attempts at cannulation, 14 (61%) transitioned successfully to EXTEND with physiologic flows (Fig.1A, n = 14), heart rate (Fig.1B, n = 14), and oxygen delivery (Fig.1C, n = 5). Animals gained an average 64% body weight and appeared to develop normally (Fig.1D). Of those cannulated, 10 completed a 10- to 21-day run, one died of an embolic cardiac arrest (day 6), 2 died of an intractable venous spasm (days 7and 8), and 1 died due to human error (day 3).Figure 1CONCLUSION: This work demonstrates that EXTEND can provide prolonged support of fetal lambs with neurodevelopmental equivalence to extremely premature human fetuses.