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Brain damage at birth: could drug treatment help babies who need cooling therapy?

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What did the project achieve?

“Studies in our laboratory model suggest that giving the drug magnesium sulphate just after birth to newborn babies with a life-threatening brain condition could help boost the benefits of cooling therapy,” says Professor Nikki Robertson of University College London.

Estimates suggest over 2,000 babies in the UK develop a life-threatening brain condition called neonatal encephalopathy (NE) each year.1,2 Caused by a shortage of oxygen to the brain around the time of birth, NE puts babies’ lives in immediate danger. Those who survive can be left with lifelong disabilities. Cooling a baby by three degrees for three days after birth gives them a better chance of surviving and escaping disability. Sadly though, this doesn’t save or protect the brain in all babies.

Professor Robertson is investigating whether giving babies with NE an existing drug called magnesium sulphate – which acts by blocking the activity of nerve connections – could help boost the protection from cooling.

“In our laboratory model, we have shown that giving an optimised dose of magnesium sulphate for 48 hours after oxygen deprivation is safe and reduces brain injury in the white matter of the brain,” says Professor Robertson.

The team plans to carry out more laboratory studies on magnesium sulphate in brain injuries involving inflammation and oxygen deprivation. They will also assess the drug in combination with a cocktail of other therapies and cooling to try to achieve the best brain protection possible.  

Professor Robertson says: “We think it is likely that the safest, most effective brain protection will be obtained by a combination of different drugs, including magnesium sulphate. We hope to be able to tailor brain protection to individual babies so that they receive the correct therapy for their type of injury.”

References:

  1. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86:329.
  2. Vital statistics in the UK: births, deaths and marriages 2018 Office for National Statistics 22 November 2019 https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/vitalstatisticspopulationandhealthreferencetables

This research was completed on

Estimates suggest around 700,000 of the world’s babies die or develop disabilities each year because of a condition called neonatal encephalopathy (NE), which can leave the brain permanently damaged.1 Often caused by a shortage of oxygen to the brain, NE puts a baby’s life in immediate danger. Cooling a baby’s temperature down for three days after birth gives them a better chance of surviving and escaping disability. Sadly though, this doesn’t save all babies. Professor Nikki Robertson, of University College London, is investigating whether drug treatment might boost the benefits of cooling and improve babies’ chances.

How are babies’ lives affected now?

“Around 1,300 babies develop a life-threatening brain condition called neonatal encephalopathy, or NE, each year in the UK,” says Professor Robertson.1,2

NE affects newborn babies in the first hours or days of life, often with devastating results. “Sadly, many babies with NE lose their lives,” says Professor Robertson. “Those who survive can develop serious lifelong problems such as cerebral palsy, epilepsy, learning difficulties and deafness.”

Cooling a baby’s temperature down by 3°C for three days – starting as soon as possible after birth – improves their chances of surviving and escaping disability.

“Cooling therapy has revolutionised the treatment of babies with NE and it is now routine in the UK,” says Professor Robertson. “Unfortunately though, cooling doesn’t benefit every baby. Experience in the UK suggests more than 40 per cent of these babies still die or develop a lifelong disability.”3

We urgently need new treatments that work with cooling to improve babies’ chances.

 

How could this research help?

“Preliminary evidence suggests a drug called magnesium sulphate might boost the benefits of cooling and improve the chances of babies with NE,” says Professor Robertson. “We are investigating the potential benefits of this combination treatment in the laboratory.”

The first aim is to identify what dose of magnesium sulphate is safest. The second aim is to find out whether using this drug in combination with cooling might increase the protective effect of treatment on the brain.

“Magnesium sulphate would be a very attractive treatment for babies with NE as it is inexpensive and widely available,” says Professor Robertson. “If our laboratory work goes well, a clinical trial in babies could be underway quite soon. Our ultimate aim is to save the lives of more babies with NE and give those who survive a better quality of life by sparing them from serious, lifelong disabilities.”

References

1. Lee ACC et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatric Research 2013; 74: 50-72.

2. Office for National Statistics. Annual Mid-year Population Estimates, 2011 and 2012. http://www.ons.gov.uk/ons/rel/pop-estimate/population-estimates-for-uk--... Website accessed 7 October 2014.

3. Azzopardi D et al. Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK – analysis of national data. PLOS One 2012; 7(6): e38504.

 

 

 

Project Leader Professor Nikki Robertson MB ChB, PhD
Project Team Professor Xavier Golay PhDDr Ilias Tachtsidis PhDDr Bobbi Fleiss PhDProfessor Pierre Gressens PhD
Project Location Institute for Women’s Health, University College London
Project Location Other Institute of Neurology, University College LondonMedical Physics and Bioengineering, University College LondonCentre for the Developing Brain, Kings College London
Project duration 1.5 years
Date awarded 25 July 2014
Project start date 23 March 2015
Project end date 31 August 2017
Grant amount £199,355
Grant code GN2295

 

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