An EXTrauterine environment for neonatal development: EXTENDING fetal physiology beyond the womb

Partridge, Emily A.; Davey, Mary‐Ann; Hornick, Matthew A.; Flake, Alan W.

doi:10.1016/j.siny.2017.04.006

Cited by 31 publications

(22 citation statements)

References 25 publications

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“…This study has demonstrated that EXTEND approximates the natural in‐utero state and creates a stable, sustainable hemodynamic construct for 3 weeks; however, there are notable effects on fetal cardiovascular physiology. Ventricular output ratios reflected RV dominance, as is the case in the normal in‐utero state; however, we found a RV‐ to LV‐CO ratio of approximately 1.4 to 1, which is lower than that found by Rudolph and Heymann using microsphere techniques, or by Acharya et al .…”

Section: Discussionmentioning

confidence: 82%

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

Ozawa

Davey

Tian

et al. 2020

Ultrasound in Obstet & Gyne

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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.

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Section: Discussionmentioning

confidence: 82%

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

Ozawa

Davey

Tian

et al. 2020

Ultrasound in Obstet & Gyne

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“…In recapitulating fetal and utero-placental physiology, an ideal AW circuit consists of a "pumpless" arterio-venous (AV) configuration allowing cardiac-driven blood flow and autoregulation. [38][39][40] From the beginning, AW technology was developed in an AV configuration. Initial models, however, required incorporation of pumps to overcome high oxygenator resistance, in order to attain physiologic fetal flows.…”

Section: Pumpless Arterio-venous Circuitmentioning

confidence: 99%

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

et al. 2020

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Extreme prematurity remains a major cause of neonatal mortality and severe long‐term morbidity. Current neonatal care is associated with significant morbidity due to iatrogenic injury and developmental immaturity of extreme premature infants. A more physiologic approach, replacing placental function and providing a womb‐like environment, is the foundational principle of artificial placenta (AP) and womb (AW) technology. The concept has been studied during the past 60 years with limited success. However, recent technological advancements and a greater emphasis on mimicking utero‐placental physiology have improved the success of experimental models, bringing the technology closer to clinical translation. Here, we review the rationale for and history of AP and AW technology, discuss the challenges that needed to be overcome, and compare recent successful models. We conclude by outlining some remaining challenges to be addressed on the path towards clinical translation and opportunities for future research.

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“…This technology maintains fluid-filled lungs that are protected from gas exchange and preserves fetal circulation. Fetal lambs that are developmentally equivalent to extremely premature neonates of 24 weeks GA have survived for up to 4 weeks using artificial placenta technology with stable hemodynamics, growth, and development [20, 21]. As this innovative model continues to achieve success, there may be an expanded use for ECMO in premature neonates.…”

Section: Future Directionsmentioning

confidence: 99%

Reconsidering ECMO in Premature Neonates

2020

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Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for neonates with respiratory failure or congenital cardiac disease refractory to maximal medical management. Early studies showed high rates of mortality and morbidities among preterm and low birthweight (BW) neonates, leading to widely accepted ECMO inclusion criteria of gestational age (GA) ≥34 weeks and BW >2 kg. In recent years, publications involving neonates of 32-34 weeks GA have reported improved survival and decreased intracranial hemorrhage. As such, ECMO should be considered on a caseby-case basis in premature neonates as long as the risks are understood.

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An EXTrauterine environment for neonatal development: EXTENDING fetal physiology beyond the womb

Cited by 31 publications

References 25 publications

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

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

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

Reconsidering ECMO in Premature Neonates

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