To cool or not to cool? Assessing brain injury in newborns

29 Nov 2013

Dr Deirdre Murray, clinician scientist at the Health Research Board, consultant paediatrician and senior lecturer at the Department of Paediatrics and Child Health in University College Cork, and researcher with the INFANT Research Centre

Dr Deirdre Murray is looking for molecular clues to identify when a newborn’s brain has suffered early injury. She spoke to Claire O’Connell.

The cells in our bodies need oxygen, and brain cells are particularly hungry for it. But sometimes during labour and delivery a baby’s brain can experience a lack of oxygen, and in severe cases it can result in brain injury with later cerebral palsy or even death. Health Research Board clinician scientist Dr Deirdre Murray is tracking down better ways to predict which babies are likely to have been injured so they can be fast-tracked for interventions, such as cooling.

“In the developed world about 20 babies per 1,000 will be under some form of stress before they are born and they will need resuscitation,” explains Murray, who is also a consultant paediatrician and senior lecturer at the Department of Paediatrics and Child Health in University College Cork (UCC). “Out of those 20 babies about three or four will have some form of encephalopathy, where the brain cells haven’t had enough oxygen and the brain swells with cell death. In moderate cases this can lead to seizures, and in severe cases the outcome is very poor – half are likely to die and the other half will be left with cerebral palsy.”

Cool therapy

Cooling babies shortly after birth may help to protect the brain, but it’s easier said than done to know exactly which babies are in need of that treatment, explains Murray.

“It’s very difficult to predict which babies are under pressure or are undergoing perinatal asphyxia, which means there is a lack of oxygen or blood supply,” she says. “We need a marker that can tell us within the first few hours of life whether there has been significant injury.”

She and colleagues at the Health Research Board (HRB) Discovery Centre in Cork and the Karolinska Institute in Sweden are analysing umbilical cord blood as part of the HRB-funded BIHIVE study in the hope of discovering easy-to-find signals of such distress.

By analysing cord-blood samples collected from births where babies needed resuscitation, the researchers have already found many of the known adult markers of disease simply don’t show up fast enough to be measured in time, explains Murray.

“For the cooling to be effective, you need to start it within six hours of the birth, and even earlier is better,” she says. “And the markers we would normally associate with adult brain injury haven’t changed in that time frame.”

But by profiling the ‘metabolome’ of the cord blood, they can see interesting signatures of particular molecules. They are also looking at novel markers, including microRNAs, that help to control how cells work by fine-tuning gene expression.

Rapid test

Murray, who studied medicine at UCC and specialised in paediatrics in the UK and Australia before returning to UCC, is continuing to refine the search for useful signatures of molecules in the cord blood. The aim is to develop a rapid test where a sample drawn from the cord could help clinicians decide when a baby needs to be cooled or undergo some other brain-protecting therapy.

“We would hope that in a few years’ time we would have a validated marker or suite of markers that can be measured in the labour ward a few minutes after the babies being born and you would have a result back straight away,” says Murray, who is also a researcher with the recently launched Science Foundation Ireland-funded Irish Centre for Fetal and Neonatal Translational (INFANT) Research Centre. “At the moment we know about cooling, but there’s a lot of research being done around the world on other neuroprotective therapies, too, and they are also likely to work better the earlier you start them following the injury.”

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Dr Claire O’Connell is a scientist-turned-writer with a PhD in cell biology and a master’s in science communication