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MRC Seminar Series: Treating brain damage after birth

by Guest Author on 6 Jan 2021

Here, Claire Mooney, Strategic Stakeholder Engagement Manager for the Medical Research Council (MRC) and the organiser of the MRC Seminar Series, writes about the November 2020 seminar and the research being done to prevent brain damage in babies caused by birth asphyxia.

The idea of cooling a baby below normal body temperature goes against all our natural instincts. However, in his efforts to prevent the consequences of severe oxygen starvation during birth (birth asphyxia), Professor David Edwards (Professor of Neonatology at MRC Centre for Neurodevelopmental Disorders) and his colleagues were among those who pioneered a technique that does exactly that. At the November edition of the MRC Seminar Series, he told us the fascinating story of the discovery and implementation of mild hypothermia treatment to prevent death and brain damage in babies after birth asphyxia.

Before the discovery of cooling as a treatment for birth asphyxia the outcomes for affected infants were poor with approximately one third suffering neurodevelopmental impairment [1]. Indications for a potential treatment came in 1989 when researchers measured the levels of phosphocreatine in babies suspected of suffering birth asphyxia. Phosphocreatine is required to create the energy needed for body cells to function during low oxygen conditions – if oxygen levels are not restored, once phosphocreatine is depleted, cells cannot generate energy and cell death leading to brain damage will begin to occur. The researchers discovered that there is a period of several hours after birth before levels of phosphocreatine decline. This suggested a delay between the occurrence of asphyxia and the onset of cell death and offered the potential for administering a treatment during this crucial time period.

The idea of inducing hypothermia after birth to prevent damage from hypoxic conditions came from the field of cardiology which had an established practice of this technique in adults during certain bypass surgeries [2]. After successful results in preclinical trials, various international clinical trials to study the effects of hypothermia on death prevention and brain damage in infants followed, including the MRC-funded TOBY trial that Professor Edwards was involved in. The TOBY trial was the largest of all the trials and independently showed a statistically significant positive effect of hypothermia on improved neurologic outcomes in survivors of birth asphyxia. While it alone did not show a significant effect on deaths after birth asphyxia, when the results from various clinical trials were pooled together, they indicated that mild hypothermia significantly reduced the occurrence of death. Additionally, in a follow-up study of the children in the TOBY trial at ages 7-8 years old, the incidence of cerebral palsy was also significantly less in the children who were treated with hypothermia after birth as infants.

Brain cooling was adopted as a therapy in the UK in 2006 and the numbers of babies being treated this way increased over the following four years. Despite its success for some, Professor Edwards acknowledged that the treatment is not perfect as, sadly, many babies do not experience the positive outcomes of others. Additionally, the success rate of the treatment is poor in low income countries because neonatal intensive care is not available alongside cooling. Other factors such as infections and increased duration and severity of hypoxia may also contribute to reduced treatment success rates. However, research continues in order to find additional therapies that can be used to treat birth asphyxia. Professor Edwards and his team identified a promising candidate drug, Xenon, which showed excellent results in rodents but unfortunately did not have any effect in humans. Another European clinical trial for a different drug, Allopurinol, is currently ongoing and may offer some alternative treatments to improve the outcomes after birth asphyxia [3].

Throughout his presentation, Professor Edwards referenced the successful development of the first baby he treated with cooling after birth asphyxia. It was remarkable and inspiring to see the real-life impacts that his work, which was partly MRC-funded, can have on people’s lives. Like many areas of medical research, there is more work to do and MRC will continue to fund impactful research that makes a difference to people’s lives.

Click here to watch the full video of Professor Edwards’ seminar.

Click here for other seminars from the MRC Seminar Series.

[1] Ahearne et al World J Clin Pediatr. 2016 Feb 8; 5(1): 67–74.

[2] Fernández Suárez et al 2017 J Thorac Dis. 2017 May; 9(Suppl 6): S508–S520.

[3] Maiwald et al 2019 BMC Pediatrics volume 19, Article number: 210.

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