What is the issue?
As a baby's brain develops during pregnancy, it is susceptible to damage. A number of factors can increase the risk of injury to the developing brain of both preterm (before 37 weeks of pregnancy) and term (after 37 weeks of pregnancy) babies. This injury can lead to death of the baby, or if the baby survives, to life-long health problems, such as hearing, sight and speech disorders; seizures; intellectual disabilities; and motor impairments, including cerebral palsy, which is the most common physical disability in childhood. Being born preterm, small-for-gestational age, or low birthweight; abnormalities of the mother's placenta (the organ that connects the developing fetus to the uterine wall); uterine infection; and birth asphyxia, caused by a lack of oxygen to the baby that lasts long enough to cause harm, can increase the risk of brain injury and cerebral palsy with associated impairments or disabilities.
Melatonin is a small hormone that is usually made by the pineal gland (a small gland in the brain) during the night. It helps to regulate the sleep-wake cycle, is an antioxidant (that protect cells from the damage caused by free radicals), and interacts with the immune system (the structures and processes in the body that protect against disease).
Why is this important?
It is possible that melatonin, given to a mother in pregnancy, can help protect her baby's brain. Animal studies, including in mice, rats and sheep, have suggested that melatonin may be able to protect the developing human baby's brain from injury when given to the mother during pregnancy.
What evidence did we find?
We did not find any completed randomised controlled trials that assessed melatonin given to the mother during pregnancy to help protect the baby's brain. One ongoing trial (planning to include 60 women) was identified. This trial is designed to determine what dose of melatonin can reduce brain injury for babies when given to their mothers before very preterm birth (before 28 weeks of pregnancy).
What does this mean?
Further studies are needed to establish whether melatonin given to the mother in pregnancy can protect the baby's brain against brain injury. The babies in these trials need to be followed up over a long period so that we can monitor the effects of melatonin on childhood development, including impairments or disabilities such as cerebral palsy.
As we did not identify any randomised trials for inclusion in this review, we are unable to comment on implications for practice at this stage.
Although evidence from animals studies has supported a fetal neuroprotective role for melatonin when administered to the mother during pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant women have been completed to date. However, there is currently one ongoing randomised controlled trial (with an estimated enrolment target of 60 pregnant women) which examines the dose of melatonin, administered to women at risk of imminent very preterm birth (less than 28 weeks' gestation) required to reduce brain damage in the white matter of the babies that were born very preterm.
Further high-quality research is needed and research efforts should directed towards trials comparing melatonin with either no intervention (no treatment or placebo), or with alternative agents aimed at providing fetal neuroprotection (such as magnesium sulphate for the very preterm infant). Such trials should evaluate maternal and infant short- and longer-term outcomes (including neurosensory disabilities such as cerebral palsy), and consider the costs of care.
Melatonin is an antioxidant with anti-inflammatory and anti-apoptotic effects. Animal studies have supported a fetal neuroprotective role for melatonin when administered maternally. It is important to assess whether melatonin, given to the mother, can reduce the risk of neurosensory disabilities (including cerebral palsy) and death, associated with fetal brain injury, for the preterm or term compromised fetus.
To assess the effects of melatonin when used for neuroprotection of the fetus.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016).
We planned to include randomised controlled trials and quasi-randomised controlled trials comparing melatonin given to women in pregnancy (regardless of the route, timing, dose and duration of administration) for fetal neuroprotection with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of melatonin.
Two review authors planned to independently assess trial eligibility, trial quality and extract the data.
We found no randomised trials for inclusion in this review. One study is ongoing.