Inexpensive drug may prevent cerebral palsy in premature babies, new study finds

A recent study confirmed that giving a simple magnesium sulfate infusion (or “drip”) to women at risk of preterm labor can prevent their babies from developing cerebral palsy. The drug itself costs about £5 (~$6.50) per dose in England and requires hospitalization with experienced staff to safely administer the drug to the mother.

An editorial in Cochrane Database of Systematic Reviews calls for this intervention to be implemented more widely and more equitably, as it is not yet uniformly available across the world.

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

Knowing which interventions work is only part of the battle, as implementing them consistently across complex healthcare systems is far from straightforward. After seeing the results of the initial study, neonatologist Karen Luyt was inspired to ensure this life-changing intervention was offered to all eligible mothers across England.

This includes all women who go into labor before 30 weeks’ 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 consequences for children and families,” says Karen Luyt, professor of 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, could be a game changer. It is the first effective neuroprotective treatment for premature babies, preventing cerebral palsy by around 30%. We were among the first to adopt it at St Michael’s Hospital (University Hospitals Bristol & Weston NHS Trust).

“I discovered in 2014 that this potentially life-changing treatment was not widely used in England, despite high-level evidence showing it is effective in protecting premature babies from brain injury and subsequent cerebral palsy. … Our aim was to give every eligible mother in preterm labour the choice to receive magnesium sulphate and every premature baby the chance to develop fully.

“The PReCePT collaboration has successfully closed the gap between evidence and practice in England, ensuring health equity for babies living in areas of greatest socio-economic deprivation and building the evidence base for successful future implementation of perinatal interventions.”

After corresponding with the Cochrane authors, Karen began implementing the findings in her own hospital through a programme called PReCePT (Prevention of Cerebral Palsy in Preterm Labour). Designed jointly by parents and maternity staff, the programme provides practical tools and training to ensure that eligible mothers are offered magnesium sulphate.

Following the success of the programme in the five health centres in the West of England, the Health Innovation Network has now extended it 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 reduction of 385 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 used for other purposes,” says Lex Doyle, Honorary Professor of Neonatal Paediatrics at the University of Melbourne.

“Cerebral palsy rates appear to be lower in premature babies whose mothers received the drug, but the evidence is 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 cerebral palsy rates in early childhood.

“It is encouraging to see the increase in the use of this procedure worldwide, which is now offered to the majority of eligible mothers in many countries. However, due to the unpredictable nature of human childbirth, it is impossible to reliably achieve 100%. Some women in preterm labour give birth too quickly, without the possibility of intervention, while others have ‘false alarms’ and continue to give birth much later, even at term.”

Despite the clear evidence that magnesium sulfate is both cost-effective and life-prolonging, not all mothers receive it. The Vermont Oxford Network collects data from over 1,400 participating neonatal units worldwide, primarily in the United States. Their data suggest that about two-thirds of eligible women receive magnesium sulfate, and this figure is likely lower in low-resource settings that are underrepresented in the data.

Karen has worked alongside clinicians around the world to develop tools to enable people in resource-poor settings to use magnesium sulphate alongside other interventions to help preterm babies. In her new editorial published in the Cochrane Library, she calls for increased global adoption and research into implementation in resource-poor settings.

“The combined trials in our review all come from high-income countries, where hospitals are relatively well equipped to administer magnesium sulphate infusions and meet 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 is not always possible. It would be useful for future studies to establish the minimum effective dose and alternative or simpler treatment regimens, particularly intramuscular administration, to facilitate widespread implementation, including in low- and middle-income countries.

“We need to continue our research to explore other questions and optimize the implementation of treatment. For example, is it better to give the drug as soon as women present to the hospital in preterm labor, or as close to delivery as possible? Are the benefits the same regardless of how early the baby is born?”

“We are currently conducting a new research project to explore some of these questions by building on existing evidence, which we hope will help standardise international recommendations and facilitate their translation. Our hope is that women whose children are unlikely to benefit from these treatments will not be exposed unnecessarily and that all women whose children are likely to benefit will be offered treatment worldwide.”

Provided by Cochrane