Inexpensive drug can prevent cerebral palsy in premature babies, new review says

Giving women at risk of premature birth a simple magnesium sulfate infusion (or ‘drip’) can prevent their babies from developing cerebral palsy, a recent review has confirmed. The drug itself costs approximately £5 (~$6.50) per dose in England, and requires hospital admission with experienced staff to administer the drug safely to the mother.

An editorial in Cochrane Database of Systematic Reviews calls for this intervention to be implemented more widely and equitably, as it is still not consistently available worldwide.

The first Cochrane review showing that magnesium sulfate 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 labor 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 a lifelong impact on 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 realized that magnesium sulfate, given to mothers in preterm labor, 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. … Our goal was to give every eligible mother in preterm labor the choice to receive magnesium sulfate 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 program called PReCePT (prevention of cerebral palsy in pre-term labor). Co-designed by parents and maternity ward staff, the program provides practical tools and training to ensure eligible mothers are offered magnesium sulfate.

Following the successful spread of the program 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 sulfate 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 sulfate 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 Pediatrics 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. Randomized 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 labor 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 sulfate 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 U.S.. Their data suggests that around two thirds of eligible women receive magnesium sulfate, 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 sulfate 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 sulfate infusions and fulfill 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 labor, 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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