COMMERCIAL PROFILE - SCIENCE FOUNDATION IRELAND:The Neonatal Brain Research Group has made great advances in detecting and monitoring newborn babies at risk of brain injury

THE LONG-TERM health outcomes of newborn babies suffering with neurological problems could be dramatically improved thanks to research being undertaken by the Neonatal Brain Research Group (NBRG) at University College Cork (UCC). The group has brought together researchers from medicine, engineering, computer science and business information systems to develop improved means of detecting and monitoring neurological emergencies such as seizures and hypoxia in neonatal intensive care units (NICUs).

The NBRG has its origins in research carried out by its leader Geraldine Boylan in King's College Hospital London in the 1980s. "I went to London back in the 1980s because I was interested in neuroscience research and there was no real funding for it here at the time," she says.

"At the time no one really considered that newborn babies could have brain injuries. Their breathing, their heart rate, their blood pressure were all monitored, but not their brains. I started researching neonatal brain injuries back then."

Brain injury in newborn babies, sometimes caused by a lack of oxygen around the time of birth, can result in cerebral palsy, mental retardation, learning disabilities and epilepsy.

With the benefit of several years' research behind her she decided to return home to Ireland in 2002 to continue the work. "I was lucky that a colleague had contacts in UCC and found an opening for me here," says Boylan. "I got a small grant from the Irish Brain Research Foundation (now the Irish Institute for Clinical Neuroscience) to begin research into the area here."

The first step in the research was to actually detect the seizures at an early stage. This is absolutely critical in newborns as the seizures themselves can cause further longer-term damage and treatment needs to begin as soon as possible, ideally within 24 hours of birth.

"When babies have seizures most of them are silent," she explains. "Babies have very immature nervous and motor systems so quite often they can just lie there having lots of seizures without anyone noticing. It was quite startling the number of seizures we detected when we started monitoring the babies with electroencephalograms (EEGs) in London."

She is quick to point out that this only applies to a tiny number of babies born each year. "I am always careful talking about this as I don't want to panic people. I am only talking about babies who may have suffered some brain injury through lack of oxygen or blood supply prior to birth or during labour or who are very premature; babies who have to be brought to the neonatal intensive care unit."

The advantages of having EEG monitors in neonatal intensive care units are enormous. "If you wait too long before carrying out an EEG you miss the treatment window. Also, if you do an EEG within 24 hours you get an excellent prognosis for the baby. In fact, you can accurately predict the outcome for 95 per cent of babies under these circumstances. This is not only good for deciding on treatment, but it is great for parents who want to know how their babies are going to be in the future."

It is also vital in deciding on treatment. "There is now a therapy for babies who are suffering from a brain injury as a result of a lack of oxygen or blood flow," Boylan notes. "It involves cooling them down within six hours of the injury occurring and an EEG can tell which baby should get this treatment. This shows how important it can be to monitor the brain during the neonatal period."

But simply putting EEG units into neonatal ICUs is not enough. Most of Ireland's neonatal units do not have neurophysiological expertise readily available to them.

The EEG trace of a newborn is also profoundly different to an adult's trace in that highly specialist expertise is required.

This absence of expertise led directly to a Science Foundation Ireland (SFI) funded research project which is aimed at developing an EEG unit which will automatically alert medical staff to seizures in newborn babies. "The first task is to detect the seizures," says Boylan. "And we are now developing an automated seizure detection algorithm. To do this we have brought together a mix of medical, engineering and computer science researchers all working together as a team. The SFI funding gave us the chance to involve the engineers. We couldn't have developed the algorithm without them."

The engineering and computer scientists have developed an algorithm which takes the signals from the neonatal EEG, processes them and analyses them to establish if a seizure is taking place. The algorithm which has been detected by the group successfully detects 95 per cent of all seizures at present.

"We had to develop a specific algorithm for neonatal EEGs," she says. "It has to be able to filter out a lot of other signals which can be picked up by EEG sensors. For example, muscle twitches can show up and there is an awful lot of electrical equipment in an ICU. We developed the algorithm to work in an offline mode and last year we got further funding from the Wellcome Trust to bring the technology to the cotside."

The big difference is that while the algorithm does what it is intended to do in terms of identifying which EEG traces are indicative of seizures, it does not do so in real time. It does this in isolation on a computer running in a lab. The next step is to have it incorporated into an actual EEG unit and have it running in real time.

This is where the group's collaboration with medical devices company CareFusion comes in. "We first came across CareFusion a number of years ago when they were a small Icelandic-owned company," says Boylan. "They had an EEG which had a video monitoring system built in. This was very useful to us as the babies aren't watched 24 hours a day so we are able to use it to see if there are any physical signs occurring at the same time as a seizure. The company showed itself to be very open to feedback from us in terms of suggested improvements to the equipment and so on, so we developed a close relationship with them over the years."

Since then, CareFusion has been the subject of a number of acquisitions - most recently by US healthcare giant Cardinal Health - but the close relationship remains. "Once we developed the algorithm we had a choice. We could set up our own company and start working on developing a new piece of equipment, but that would take too long and we need this soon. CareFusion has worked with us as a partner on the project and has given us full access to its software and codes and its R&D centre in Madison, Wisconsin, became involved as well. We have now patented the algorithm and we may license it to CareFusion once clinical trials are completed, which we hope will be in 2011."

The EEG with this algorithm built in will be able to alert a neonatologist either by visible signals on the machine itself or even by a mobile phone text message. But that still does not deal with the absence of neurophysiological expertise on-site which is where further SFI-funded research by the group comes in.

"We are working with the Boole Centre for Research in Informatics here in UCC to develop a system whereby the EEG information can be sent over the web to any device, such as a laptop or even an iPod which can run Flash Player. Our long-term goal is to use this system to deliver the EEG information to experts, wherever they are, who can decide if a baby is suitable for cooling treatment or not."

The Neonatal Brain Research Group is now recognised as an international leader in its field and continues to move closer to its goal of having intelligent neurological monitoring available in neonatal intensive care facilities throughout Ireland and beyond. "This wouldn't have been possible without the SFI research funding which enabled us to bring together the great team that we have. But it's not just having the different disciplines on the team that matters. You have to have buy-in from all the members and an understanding of the clinical need for what we are doing. You also need buy-in from an industry partner like CareFusion to make things happen," Boylan says.