Fetal echocardiographic assessment of cardiovascular impact of prolonged support on EXTrauterine Environment for Neonatal Development (EXTEND) system

Abstract

Objective EXTrauterine Environment for Neonatal Development (EXTEND) is a system to support ongoing fetal growth and organ development in an extrauterine environment, utilizing a pumpless low‐resistance oxygenator circuit. The aim of this study was to evaluate hemodynamics and cardiac function in fetal sheep sustained on the EXTEND system. Methods This was a prospective study of fetal sheep supported for a minimum of 3 weeks on EXTEND. Hemodynamic parameters were assessed weekly and included heart rate, mean arterial pressure (MAP), Doppler‐echocardiography‐derived cardiac output (CO), pulsatility indices (PIs) of the fetal middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus and cardiac function, as assessed by speckle‐tracking‐derived global longitudinal strain and strain rate in the right (RV) and left (LV) ventricles. Parameters were compared at 0 days and 1, 2 and 3 weeks following placement on EXTEND. Results Of 10 fetal sheep enrolled, seven survived for 3 weeks and were included in the analysis. Median gestational age at cannulation was 107 (range, 95–109) days. Heart rate decreased and MAP increased significantly, but within acceptable ranges, during the study period. The quantities and relative ratios of right and left CO remained stable within the anticipated physiological range throughout the study period. Vascular tracings and PIs appeared to be similar to those seen normally in the natural in‐utero state, with MCA‐PI being higher than UA‐PI. UA tracings demonstrated maintained abundant diastolic flow despite the absence of placental circulation. In both the RV and LV, strain decreased significantly at 1 and 2 weeks relative to baseline but returned to baseline values by week 3. Conclusions The EXTEND mechanical support system replicates natural physiology and creates a stable and sustainable cardiovascular construct that supports growth over a 3‐week period. However, there is a period of depressed contractility within the first week with subsequent improvement by week 3. This may reflect a period of physiological accommodation that warrants further investigation. This study lays the foundation for further exploration as the EXTEND system moves towards human application. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation

“…Neurodevelopmental maturation in lambs on circuit was demonstrated by progressive consolidation of sleep/wake cycles measured with ocular electromyography. Reduced cardiac contractility was temporarily noted during a 1‐week accommodation phase on circuit, after which normal cardiac function and contractility were present for the rest of the run 115 . In lambs supported by EXTEND for 19 to 25 days, no myocardial injury or inflammation was found, and cardiac development and structure was normal compared to age‐matched controls 116 .…”

In case you missed it: The Prenatal Diagnosis editors bring you the most significant advances of 2019

“…In 2019, several groups have shown that important components of fetal physiology are maintained on artificial placental support and develop more naturally than in a ventilated newborn. Stable cardiovascular physiology has been shown both in short‐ and in long‐term experiments using a pumpless system . Even after longer term support, animals can be transitioned to normal care and maintain normal behaviour and mitochondrial respiration .…”

“…Stable cardiovascular physiology has been shown both in short-and in long-term experiments using a pumpless system. 54,55 Even after longer term support, animals can be transitioned to normal care 53 and maintain normal behaviour and mitochondrial respiration. 56 Previous experiments with a pump-driven system had already shown that fetal splenic development 57 and cerebral oxygenation can be maintained 58 and that white matter integrity is preserved with this type of life support.…”

Development of an artificial placenta for support of premature infants: narrative review of the history, recent milestones, and future innovation

“…They did note a consistent gradual decline in weightadjusted flow over the course of the runs for which no clear cause could be identified. A subsequent study used echocardiography to identify increased heart strain in the first two weeks of support on EXTEND with return to baseline by the third week (62). They demonstrated four weeks of support with hemodynamic stability, maintenance of fetal circulation, adequate gas exchange, and evidence of fetal growth (63).…”