Predicting Brain Damage in Children with Acute Brain Injuries

Professor Brian Darlow Cure Kids Professor of Paediatric Research Department of Paediatrics University of Otago Christchurch
BOOST-NZ STUDY SEEKS ANSWERS FOR PRE-TERM BABIES

Background to the research

 Oxygen is the commonest neonatal therapy. Unfortunately, both too much and too little oxygen may be harmful for very premature infants. We now measure the oxygen in a baby’s blood by oxygen saturation but the optimum range in the first few weeks is unknown. The BOOST-NZ study is the New Zealand arm of a major international randomised controlled trial involving 5000 babies, born at less than 28 weeks, which is addressing this question. In the BOOST-NZ study babies are randomised to a higher or lower target range of oxygen saturation from birth (85-89% or 91-95%). The study aims to assess which of the target ranges has the best overall outcome.

Our proposal is for an important add-on to the BOOST-NZ study, namely undertaking cranial MRI scans at the date at which the baby would have been born if it was full term (term equivalent).  Our group has previously shown many very preterm babies have abnormal findings on MRI scans at this time, which may predict neurodevelopmental outcome. We now aim to see if there are different patterns of abnormality in babies randomised to higher or lower oxygen saturation.

What are your research objectives?

 To carry out cranial MRI scans at term equivalent in 100 New Zealand infants born at <28 weeks gestation and randomised to a higher or lower oxygen saturation target. We want to determine if there is a different pattern of white matter injury (white matter is the ‘telephone network’ connections between brain cells) and grey matter abnormality seen in very preterm infants randomised to higher or lower oxygen saturation targets.

How will the research be conducted?

 We will approach families of infants enrolled in the BOOST-NZ study in Christchurch and National Women’s NICUs for consent to undertake a cranial MRI scan at term equivalent.

To undertake the cranial MRI scan infants are fed, wrapped and settled in a vacuum extracted bean-bag pillow. General anaesthesia or sedation is not used. The procedure is very well tolerated by infants. The scans will be read independently by one of two radiologists and a proportion co-read to establish a statistical measure of agreement between them. The radiologists who read the scans will use a standardised method to score any abnormalities and they will not be aware the oxygen saturation target assignment. We will also be able to compare findings with the standard method of cranial imaging, namely using ultrasound, which is a routine part of care for very pre term infants.

What is innovative about your approach?

 The BOOST-NZ study is part of an international collaboration involving 5000 babies in Australia and New Zealand, North America and Europe and is the first ever randomised trial of oxygen saturation targeting carried out in very preterm infants. No other group contributing to the international study is planning to carry out MRI scans at term equivalent. Our group has extensive experience in undertaking such scans in very preterm infants and has shown that three-quarters of infants of <32 weeks gestation have some evidence of white matter injury but with a variable pattern. Depending on the results of the oxygen targeting studies it is likely that either strategy (higher or lower targeting) may be adopted as standard and hence there will no longer be an opportunity to carry out a similar cranial MRI study in the future.

How will the study benefit participants and advance knowledge?

Cranial MRI scans at term equivalent can more fully characterise any brain injury or delayed development associated with very preterm birth, although such scans are yet part of routine care. This knowledge may help with design of an individualised early intervention programme for that infant.

The study will provide information on brain injury patterns acquired by very preterm infants cared for with either a lower or a higher oxygen saturation target, information which it is only possible to acquire in the context of an ongoing randomised controlled trial. The information will lay the foundation for future research to further decrease adverse outcome from extreme prematurity.

Is there national or international collaboration?   

As noted above, the BOOST-NZ trial is part of a major international collaborative effort. The present study is a collaboration between researchers in Christchurch and National Women’s hospitals.