Inexpensive drug can prevent cerebral palsy in premature babies

The first Cochrane review showing that magnesium sulphate protects premature babies against cerebral palsy was published in 2009, and the recent update includes newer trials which further confirm this finding. It has been recommended by the World Health Organization since 2015 for women at risk of premature birth before 32 weeks of gestation, but implementation remains a challenge in many areas.

Knowing which interventions are effective is only part of the battle, as implementing them consistently across complex health systems is far from trivial. After seeing the results of the original review, neonatologist Karen Luyt was inspired to ensure this life-changing intervention was offered to all eligible mothers across England. This includes all women going into labour before 30 weeks of gestation, and some women between 30 and 33 weeks depending on clinical factors.

“Preterm birth is the leading cause of brain injury and cerebral palsy with lifelong impact on children and families,” says Karen Luyt, Professor in Neonatal Medicine at the University of Bristol. “When the Cochrane meta-analysis was published in 2009, I realised that magnesium sulphate, given to mothers in preterm labour, was a potential game changer. The first effective neuroprotective treatment for preterm babies, preventing cerebral palsy by around 30%. We were early adopters at St Michael’s Hospital (University Hospitals Bristol & Weston NHS Trust).

“I discovered in 2014 that this potentially life altering treatment was not widely used in England, despite high level evidence that it is effective at protecting preterm babies from brain injury and subsequent cerebral palsy. I was awarded Evidence to Practice Challenge support funding from our West of England Health Innovation Network and the PReCePT project was born. Our goal was to give every eligible mother in preterm labour the choice to receive Magnesium Sulphate and for every preterm baby the chance to develop to their full potential.

“The PReCePT collaboration managed to close the evidence-to-practice gap in England, achieve health equity for babies living in the most socio-economically deprived regions and build the evidence base for successful future implementation of perinatal interventions.”

Following correspondence with the Cochrane authors, Karen began implementing the findings in her own hospital through a programme called PReCePT (prevention of cerebral palsy in pre-term labour). Supported by Health Innovation West of England and co-designed by parents and maternity ward staff, the programme provides practical tools and training to ensure eligible mothers are offered magnesium sulphate.

One of the first women to receive magnesium sulphate through the programme was Elly Salisbury. She was offered the drug when pregnant with her son Cormac, who is now a healthy 11-year old boy.

“It fills me with pride and joy that all mothers in my situation across England are offered magnesium sulphate thanks to the PReCePT programme,” says Elly. “Behind every infusion of magnesium sulphate is a little boy or girl, just like Cormac, and a family just like ours. Every family deserves the chance to be given this drug, wherever they are in the world. I hope that health systems around the world take inspiration from PReCePT’s success to make this a reality.”

Following the successful spread of the programme to all five trusts in the West of England, the Health Innovation Network has now rolled it out to all NHS maternity units in England. Between 2018 and 2023, magnesium sulphate was given to 14,270 eligible women across the country, resulting in an estimated 385 fewer cases of cerebral palsy.

The widespread use of this life-changing treatment was made possible by the original Cochrane review led by Professors Lex Doyle and Caroline Crowther.

“The first suggestions that magnesium sulphate might protect babies’ brains from cerebral palsy came from observational studies where it was being used for other purposes,” says Lex Doyle, Honorary Professor of Neonatal Paediatrics at the University of Melbourne. “Rates of cerebral palsy appeared to be lower in premature babies whose mothers had received the drug, but the evidence was inconclusive. Randomised clinical trials followed, and when we published our 2009 review which combined the results of five trials, the evidence showed a clear benefit in reducing rates of cerebral palsy in early childhood.

“It’s heartening to see the increased uptake of this intervention around the world, which is now being given to the majority of eligible mothers in many countries. However, due to the unpredictability of human childbirth, it’s impossible to reliably reach 100%. Some women in preterm labour deliver too quickly, with no opportunity for intervention, while others experience ‘false alarms’ and go on to give birth much later, even at term.”

Despite clear evidence that magnesium sulphate is both cost-effective and life-changing, not all mothers are receiving it. The Vermont Oxford Network collects data from over 1,400 participating neonatal units worldwide, primarily in the USA. Their data suggests that around two thirds of eligible women receive magnesium sulphate, and this figure is likely to be lower in low-resource settings that are underrepresented in the data.

Karen worked alongside clinicians around the world to develop materials to help people in lower-resource settings to implement magnesium sulphate alongside other interventions to help premature babies. In her new editorial in the Cochrane Library, she urges increased global uptake and implementation research in lower-resource settings.

“The trials combined in our review are all from high-income countries, where hospitals are comparatively well set-up to administer magnesium sulphate infusions and fulfil maternal and fetal monitoring requirements,” says Dr Emily Shepherd of the South Australian Health and Medical Research Institute, lead author of the updated Cochrane review. “In low resource settings, this may not always be possible. It would be helpful for future studies to establish the minimum effective dose, and alternative or simpler regimens, particularly intramuscular administration, to aid widespread implementation including across low and middle-income countries.

“We need further research to explore other questions to help optimize implementation. For example, is it better to deliver the drug as soon as women present to hospital in preterm labour, or as close to the birth as possible? Are the benefits the same regardless of how early the babies are born? We are currently undertaking a new research project to explore some of these questions based on existing data, which we hope will help to standardize international recommendations and aid translation. Our hope is that women whose children will likely not benefit are not exposed unnecessarily, and that all women whose children are likely to benefit are offered treatment across the globe.”

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Notes to editors:

‘Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus’ by Shepherd et al. is published in the Cochrane Database of Systematic Reviews: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004661.pub4/full

‘Antenatal magnesium sulphate reduces cerebral palsy after preterm birth, implementation into clinical practice needs to be accelerated globally to benefit preterm babies’ by Professor Karen Luyt will be published as an editorial in the Cochrane Library when the embargo has lifted at the following URL: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.ED000168