Key messages
- Neonatal encephalopathy (abnormal brain function in the first days of life) is a major cause of death and disability in children.
- Our review demonstrated that the evidence for melatonin treatment in neonatal encephalopathy is very uncertain.
- More studies are needed to assess if melatonin should be used for newborns with neonatal encephalopathy.
What is neonatal encephalopathy?
Neonatal encephalopathy is a condition of disturbed brain function in the first few days of life, which is caused by a lack of oxygen or blood flow to the brain before or around the time of birth. After a lack of oxygen or blood supply, newborn brain cells continue to be harmed for a long time after normal supply has returned.
What is the usual treatment for neonatal encephalopathy?
Usual treatment for neonatal encephalopathy is critical care support, often in the intensive care environment, and includes cooling therapy in high-income countries (e.g. USA, Australia, UK). Cooling therapy (known as therapeutic hypothermia) is given in these countries to newborns with moderate to severe neonatal encephalopathy; however, cooling is not usual treatment in low to middle-income countries.
How could melatonin help newborns with neonatal encephalopathy?
Treatment with melatonin, a hormone that occurs naturally in the body, may help to prevent further damage to brain cells if given shortly after birth. Melatonin can be given either by mouth or by a drip directly into the vein. If it were an effective treatment, giving melatonin to newborns with neonatal encephalopathy would result in more children surviving, and more children surviving without physical or learning disabilities.
What did we want to find out in this review?
We wanted to examine whether melatonin treatment results in better outcomes for newborns with neonatal encephalopathy. We examined two separate treatment comparisons: melatonin treatment in combination with cooling compared to cooling treatment alone; and melatonin treatment alone compared to standard treatment without cooling.
What did we do?
We searched for studies that compared the effects of melatonin treatment to standard treatment (with or without cooling therapy) in newborns with neonatal encephalopathy. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What were our main results?
We found four studies of 155 participants that compared melatonin treatment to standard treatment with or without cooling therapy.
We are very uncertain about the effects of melatonin treatment on
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the combined outcome of death or disability when measured at 18 months of age or over;
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death in the first month of life;
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disability, measured at 18 months of age or over; and
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abnormalities on an MRI (magnetic resonance imaging) brain scan (measured in the grey matter and white matter areas of the brain) in the first month of life.
No study reported on the effects of melatonin treatment on
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multiorgan failure; or
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the need for anti-seizure medicine.
Overall, the evidence is very uncertain. Therefore, we cannot draw any conclusions about whether or not melatonin treatment can improve outcomes for newborns with neonatal encephalopathy.
What are the limitations of the evidence?
We included only four small studies in this review. Many outcomes that we considered important were reported only in part or were not reported at all. Therefore, we are very uncertain about the effects of melatonin treatment compared to standard treatment (with or without cooling therapy) for newborns with neonatal encephalopathy.
More studies are needed to examine the effects of melatonin on outcomes following neonatal encephalopathy.
How up to date is the evidence?
This evidence is up to date to August 2025.
Vollständige Zusammenfassung lesen
Zielsetzungen
To evaluate the effects and safety of melatonin treatment compared to standard care, with or without therapeutic hypothermia, on survival and neurological sequelae in newborns with neonatal encephalopathy.
Suchstrategie
We used CENTRAL, MEDLINE, two other databases, and two trial registers, together with reference checking and citation searching, to identify studies for inclusion in the review. The latest search date was 18 August 2025.
Schlussfolgerungen der Autoren
The available data are of very low certainty, so we cannot draw conclusions about the effects of melatonin treatment on outcomes in newborns with neonatal encephalopathy. Only one pilot study of 25 participants reported our critical outcome. The evidence is very uncertain about the effect of melatonin on death of newborns with neonatal encephalopathy or neurodevelopmental disability in the newborns who survive. We are uncertain about the effect of melatonin on mortality in the first month of life and on the incidence of abnormalities in magnetic resonance imaging of the brain. Overall, the evidence to date for melatonin treatment in neonatal encephalopathy is uncertain, and larger randomised trials are urgently required.
Finanzierung
This research was conducted as part of the NEPTuNE Collaboration, funded by the Health Research Board of Ireland.
Registrierung
Protocol available via DOI 10.1002/14651858.CD013754
