A review study of fetal circulatory models to develop a digital twin of a fetus in a perinatal life support system

Abstract

BackgroundPreterm birth is the main cause of neonatal deaths with increasing mortality and morbidity rates with decreasing GA at time of birth. Currently, premature infants are treated in neonatal intensive care units to support further development. However, the organs of, especially, extremely premature infants (born before 28 weeks of GA) are not mature enough to function optimally outside the womb. This is seen as the main cause of the high morbidity and mortality rates in this group. A liquid-filled incubator, a so-called PLS system, could potentially improve these numbers for extremely premature infants, since this system is designed to mimic the environment of the natural womb. To support the development and implementation of such a complex system and to interpret vital signals of the fetus during a PLS system operation, a digital twin is proposed. This mathematical model is connected with a manikin representing the digital and physical twin of the real-life PLS system. Before developing a digital twin of a fetus in a PLS system, its functional and technical requirements are defined and existing mathematical models are evaluated.Method and resultsThis review summarizes existing 0D and 1D fetal circulatory models that potentially could be (partly) adopted for integration in a digital twin of a fetus in a PLS system based on predefined requirements. The 0D models typically describe hemodynamics and/or oxygen transport during specific events, such as the transition from fetus to neonate. Furthermore, these models can be used to find hemodynamic differences between healthy and pathological physiological states. Rather than giving a global description of an entire cardiovascular system, some studies focus on specific organs or vessels. In order to analyze pressure and flow wave profiles in the cardiovascular system, transmission line or 1D models are used. As for now, these models do not include oxygen transport.ConclusionThis study shows that none of the models identified in literature meet all the requirements relevant for a digital twin of a fetus in a PLS system. Nevertheless, it does show the potential to develop this digital twin by integrating (parts) of models into a single model.

Transferring an extremely premature infant to an extra-uterine life support system: a prospective view on the obstetric procedure

“…A protocol that specifies the maximum duration of cannulation, identifies the key clinical parameters that indicate deterioration, and emphasizes the importance of promptly discontinuing the procedure before the onset of irreversible damage, such as decreased cerebral oxygenation, should be established. Future preclinical studies should identify all the relevant parameters and their threshold values, which could be aided by the development of a clinical decision support system ( 155 ). It is essential that these criteria are unambiguous, and that the parties responsible for making the decision to cease the transfer are clearly delineated.…”

“…Research suggests that medical simulation may improve obstetric team performance and maternal and perinatal outcomes ( 184 ). Medical simulation has also been proposed within an APAW context to complement the development of procedures tailored to human patients ( 5 , 155 , 185 ). Although in silico studies should ultimately be followed by validation in vivo , the emergence of novel simulation technologies could offer an intermediary step that allows for a controlled and safe environment for procedural development and training.…”

Simulation-based development: shaping clinical procedures for extra-uterine life support technology

“…This could be done by quantifying the proficiency of a certain task as a function of time-to-completion, and the parameter values of vital organs can be monitored to visualize the reaction-time of a certain task to presented symptoms [ 16 , 83 ]. Physical fetal manikins with embedded digital twin technology [ 84 ] can, in this context, be used to train clinical decision-making. Furthermore, team dynamics can be rehearsed for alignment.…”

Maternal and fetal health in the digital twin era

“…As reported, a dynamic DTs represents a useful strategy for prevention, diagnosis, therapy and prediction of disease during the life in a individual who experienced hypertension during periconception, optimizing children health care ( 12 ). Recently an integration between DTs and fetal circulatory models has been also proposed to develop and implement the perinatal life support system ( 20 ).…”