Abstract
Introduction: Preterm birth is the leading cause of infant mortality and morbidity. Artificial placenta (AP) technology aims to support premature fetal piglets in an environment simulating intrauterine physiology to maintain fetal circulation and improve outcomes and survival. Hypothesis: We sought to understand the fetal cardiovascular physiology and mode of cardiac failure associated with a pumped extracorporeal membrane oxygenation circuit connected to the fetal circulation. Methods: Following umbilical cannulation, connection to a centrifugal pump and neonatal oxygenator and transition of preterm Yucatan miniature piglets to a fluid-filled biobag, echocardiographic studies measured ventricular function and fluid status including Dopplers, and strain analysis both prenatally and while maintained on the AP circuit. Results: AP fetuses (n=13; GA 102±4d; 616±139g; survival 46.4±46.8h) were tachycardic and hypertensive with supraphysiologic circuit flows initially. Strain analysis revealed significantly reduced RV strain rate within the first five hours of AP support compared to paired prenatal measurements (p=0.005) . Fetuses supported for <24h had significantly lower overall RV global longitudinal strain (p=0.001) than those surviving >24h. M-mode imaging revealed progressive cardiac hypertrophy with an increase in interventricular septum (p=0.03) and LV free (p=0.04) wall thickness from first to last measurements. Doppler measurements showed elevated peak flow velocity patterns in the MCA and reductions in MCA-PI from start to end of support (p=0.04) as well as compared to unpaired prenatal controls (p=0.03, p=0.001) . Imaging findings included ascites, skin edema, and dilated hepatic veins. Conclusions: AP fetuses exhibited signs of excessive volume and pressure loading resulting in impaired contractility, including supraphysiologic umbilical flows, reduced RV strain and strain rate, and evidence of elevated filling pressures. Myocardial hypertrophy and changes in cerebral perfusion indicated adaptation to increased afterload, potentially affecting cardiovascular and cerebrovascular development and leading to fetal deterioration. Further advancements in AP technology are necessary before clinical translation.
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