The general director of the "la Caixa" Foundation, Antonio Vila Bertrán; the general director of the Hospital Clínic Barcelona, Josep Maria Campistol; the managing director of the Hospital Sant Joan de Déu Barcelona, Manel del Castillo; the director of BCNatal and leader of the project, Eduard Gratacós; the senior specialist of BCNatal and senior scientific coordinator of the project, Elisenda Eixarch, and the director of the Area of Relations with Research and Health Institutions of the "la Caixa" Foundation, Ignasi López, have presented the results of the first phase of the CaixaResearch Artificial Placenta project, the first experimental project in an animal model of artificial placenta in Europe.
Over the first two and a half years of work, the team led by Dr. Eduard Gratacós at BCNatal has developed a first integrated prototype of artificial placenta that has been increasing the hours of survival exponentially until reaching 12 days in good foetal conditions. This is the first milestone in this highly complex scientific project promoted by the "la Caixa" Foundation, which aims to increase survival and reduce the serious sequelae suffered by the majority of newborns aged six months or less, who are considered to be extremely premature.
To create an environment in which a very premature newborn can live as naturally and as close to the womb as possible, the first prototype developed includes a protected environment composed of a translucent container made of biocompatible material and connected to an amniotic fluid circulation system that allows the foetus to be kept in a liquid environment isolated from external stimuli, but accessible for ultrasound checks and allows continuous monitoring of the foetus.
Another of the great advances achieved so far has been the creation of an extracorporeal circulation system, consisting of an oxygenating membrane and a system of parts (tubes) specifically designed to facilitate blood circulation and oxygenation, which simulates what occurs naturally in intrauterine life thanks to the maternal placenta and the umbilical cord.
The project's interdisciplinary team has also worked on the creation of a non-invasive real-time monitoring system that enables permanent remote surveillance to be maintained in order to provide the medical team with intensive control of the state and development of the foetus. In addition, medical support protocols have been designed that include the administration of nutrition, hormones and other medications, and that foresee possible clinical scenarios and the medical actions necessary to reverse them.
In the words of Dr. Gratacós: "This is one of the most disruptive and unique research projects that can be carried out today in foetal medicine. Just having an experimental platform such as the one that will be built will allow parallel research of great importance to understand normal and abnormal foetal development. This will increase the capacity to attract investment for R&D&I in Barcelona, Catalonia and Spain, and a new generation of techniques and procedures that will revolutionise current foetal and neonatal medicine".
A second phase of experimental validation to move closer to the clinic
So far, using an ovine animal model, the team has designed and described the surgical techniques and protocols necessary to perform a smooth transition from the uterus to an artificial placenta system, and has successfully performed all transitions in the last 12 months.
After analysis and evaluation by a panel of experts from five countries, with recognised international prestige in foetal and neonatal medicine, the CaixaResearch Artificial Placenta project is now entering a second phase (2023-2026) in which it will once again have the support of the "la Caixa" Foundation, which has boosted the project with a further 4.3 million euros, in addition to the 3.35 million already granted for the first phase that is now coming to an end.
"Currently, for the families of extremely premature babies, a moment that should be a time of maximum happiness becomes a journey full of uncertainty and anguish. We share with BCNatal, the Hospital Sant Joan de Déu and the Hospital Clínic Barcelona a great enthusiasm to move forward with this project to achieve a solution that will help save lives and reduce the serious developmental sequelae that some of these newborns have", explains Antonio Vila Bertrán, director general of the "la Caixa" Foundation.
In this second phase, one of the new milestones expected to be reached during 2024 is to extend the survival time from the current 12 days to more than 3 weeks. To this end, the project team will focus its efforts on technological improvements, in collaboration with industry, to optimise the medical devices used, such as cannulas and oxygenating membranes.
In addition, during these years, the project must design and describe the protocols necessary for the transition to neonatal life, i.e. the birth of the foetus from the artificial placenta to extrauterine life, so that it begins to use its lungs like any other newborn. The team will also conduct experiments in another large animal model such as a pig to demonstrate the transferability of the system to other species, assess the long-term effects on brain, heart, lung and metabolic development, and make all the (ethical and legal) preparations for a first clinical study to be approved in the context of compassionate use therapy.
A disruptive solution to save the lives of premature newborns
Although more than 90% of pregnancies go to term normally, foetal life remains one of the most risky phases of human life. One of the major unresolved problems is extreme prematurity (six months or less), which affects 25,000 families every year in Europe alone. Survival of extreme preterm infants, even in units of excellence, is low (25-75%), and a significant proportion of survivors have sequelae.
Before six months of pregnancy, the foetus' lungs, intestines and brain are underdeveloped and not ready to function properly. An extremely premature newborn is, in reality, a foetus that must survive in a very unnatural environment. Weighing less than 1,000 grams, these newborns require respiratory support and intravenous feeding to keep them alive, but this can lead to complications and have an impact on their future life. For this reason, the artificial placenta can be a solution to improve the quality of life of these newborns.
The good results obtained by the project will be presented to the medical community at the World Congress of Fetal Medicine to be held in Valencia from 25 to 29 June this year, where there will be a specific session on artificial placenta.
The research group led by Dr. Gratacós has a strong interdisciplinary character and has the direct participation in the project of more than 35 researchers from different disciplines (various specialties of medicine, biology, engineering, nursing) and the collaboration of 35 other professionals. In addition, the project has several supervisory committees comprising experts in other fields (in reproductive rights and bioethics, among others), and mothers and fathers of premature children.
Apart from the CaixaResearch Artificial Placenta project, there are currently only four other groups in the world (Philadelphia and Michigan, in the United States; an Australia-Japan consortium, and Toronto, in Canada) that have developed experimental models with significant advances in recent years.
About BCNatal and "la Caixa" Foundation
BCNatal is a joint centre within the Agrupació Sanitària Sant Joan de Déu - Hospital Clínic Barcelona. With almost 7,000 deliveries and between 100 and 120 foetal surgeries per year, and with 600 healthcare professionals and almost 100 of them dedicated to R&D&I, BCNatal is one of the largest maternal-fetal and neonatal clinical areas in Europe. It is a pioneering clinical and research centre in foetal surgery whose specialists have developed and performed for the first time in the world some of the current techniques in foetal surgery. The centre receives doctors from all five continents for specialised training and is among those with the highest international scientific output in its field.
BCNatal has led major research projects in foetal medicine and surgery, and has extensive experience in interdisciplinary collaboration with centres of excellence in biotechnology, so it has the experience and critical mass necessary to develop a project as ambitious as the one presented.