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

A simple magnesium sulfate infusion (or “drip”) can prevent cerebral palsy in babies in women at risk of premature birth, a recent study confirms. The drug itself costs about £5 (about $6.50) per dose in England and requires hospital admission by experienced staff to safely administer the drug to the mother.

An editorial in Cochrane database of systematic reviews calls for a more comprehensive and equitable implementation of this intervention, as it is still not available across the world.

The first Cochrane review showing that magnesium sulfate protects premature babies from cerebral palsy was published in 2009. The current update includes more recent studies that further confirm this finding. The World Health Organization has recommended magnesium sulfate since 2015 for women at risk of premature birth before 32 weeks of pregnancy. However, implementation remains a challenge in many areas.

Knowing which interventions are effective is only part of the battle, because implementing them consistently in complex healthcare systems is far from trivial. After seeing the results of the original review, neonatologist Karen Luyt was inspired to ensure this life-changing intervention is offered to all eligible mothers across England.

This includes all women who go into labor before 30 weeks of pregnancy and, depending on clinical factors, some women between 30 and 33 weeks.

“Premature birth is the most common cause of brain injury and cerebral palsy, with lifelong effects 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 realised that magnesium sulphate given to mothers of premature babies could be a potential game changer. It was the first effective neuroprotective treatment for premature babies, preventing cerebral palsy by around 30%. We were the early users at St Michael's Hospital (University Hospitals Bristol & Weston NHS Trust).

“I noted in 2014 that this potentially life-changing treatment was not widely available in England, despite strong evidence that it was effective in protecting premature babies from brain damage and subsequent cerebral palsy. … Our aim was to give every eligible mother of premature birth the opportunity to receive magnesium sulphate and to give every premature baby the chance to reach their full potential.

“The PReCePT collaboration has succeeded in bridging the gap between scientific evidence and practical application in England, achieving health equity for babies in the most socioeconomically poor regions and creating the evidence base for successful future implementation of perinatal interventions.”

After exchanging letters with the Cochrane authors, Karen began implementing the findings in her own hospital through a program called PReCePT (Prevention of Cerebral Palsy in Prematurity). Developed jointly by parents and maternity ward staff, the program provides practical tools and training to ensure that magnesium sulfate is offered to eligible mothers.

Following the successful expansion of the programme to all five trusts in the West of England, the Health Innovation Network has now expanded it to all NHS maternity wards in England. Between 2018 and 2023, magnesium sulphate was administered to 14,270 eligible women nationwide, 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 evidence that magnesium sulfate could protect babies' brains from cerebral palsy came from observational studies in which it was used for other purposes,” says Lex Doyle, honorary professor of neonatal pediatrics at the University of Melbourne.

“In premature babies whose mothers had received the drug, the rate of cerebral palsy appeared to be lower, but the evidence was inconclusive. Randomized clinical trials followed, and when we published our review in 2009 summarizing the results of five studies, the evidence showed a clear benefit in reducing the rate of cerebral palsy in early childhood.

“It is encouraging to see that this procedure is becoming increasingly common around the world and that in many countries the majority of mothers who are eligible for it now receive it. However, because the birth of a child is so unpredictable, it is impossible to achieve a reliable 100% success rate. Some women with premature births give birth too quickly and do not have the opportunity to have the procedure, while others experience 'false alarms' and the baby is born much later, even on the due date.”

Although there is strong evidence that magnesium sulfate is both cost-effective and life-changing, 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. In low-resource settings, which are underrepresented in the data, this number is likely to be lower.

Karen has worked with clinicians around the world to develop materials to help people in poor settings use magnesium sulfate alongside other interventions to help premature babies. In her new editorial in the Cochrane Library, she calls for increased global uptake and implementation research in poor settings.

“The studies summarized in our report all come from high-income countries where hospitals are comparatively well prepared to administer magnesium sulfate 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 report.

“In low-resource settings, this may not always be possible. It would be helpful if future studies established the minimum effective dose and alternative or simpler treatment regimens, particularly intramuscular administration, to enable widespread implementation, including in low- and middle-income countries.

“We need to do more research to answer other questions and optimise implementation. For example, is it better to give the drug as soon as the woman comes to the hospital with preterm labour, or as soon after birth as possible? Are the benefits the same regardless of how early the babies are born?

“We are currently conducting a new research project to explore some of these questions based on existing data. We hope this will help standardise international recommendations and facilitate translation. We hope that women whose children are unlikely to benefit will not be unnecessarily exposed to treatment and that all women whose children are likely to benefit will be offered treatment worldwide.”

Provided by Cochrane