Creatine for women in pregnancy for neuroprotection of the fetus

This review did not find any randomised controlled trials that looked at whether creatine, given to a mother in pregnancy, can help protect her baby's brain.

The developing fetal brain is very vulnerable to injury, which may arise from infection in the uterus, insufficient blood flow to the placenta, and long-term reduced oxygen in the baby's blood. Damage to the developing brain during pregnancy can lead to death of the baby, or, if the baby survives, to life-long problems such as hearing, sight and speech disorders, intellectual disability, and cerebral palsy.

Creatine is involved with cellular energy production and how energy is stored for use in the body's tissue. Its primary function is to regenerate adenosine diphosphate (ADP) to adenosine triphosphate (ATP) in body tissues with high and fluctuating energy demands. Adults obtain approximately half of their daily requirement of creatine from a diet containing fresh fish, meat, and other dairy products. The body makes the remainder of the creatine from amino acids (the building blocks of proteins). Experiments in animals have suggested that creatine might be able to protect the developing fetal brain from injury when given to the mother during pregnancy. Human studies of creatine, outside of pregnancy (such as in children following traumatic brain injury, and in adults with neurodegenerative conditions), have been promising, suggesting creatine may be able to protect the brain, and these studies have been reassuring, with an absence of any detected harm.

We found no completed (or ongoing) randomised controlled trials that assessed whether creatine given to the mother at times of known, suspected, or potential fetal compromise during pregnancy helps to protect the baby's brain. Randomised controlled trials are needed to establish whether creatine can protect against brain injury for the baby in the womb. The babies in these trials need to be followed up over a long period so that we can monitor the effects of creatine on their development into childhood and adulthood.

Authors' conclusions: 

As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

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Background: 

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury.

Objectives: 

To assess the effects of creatine when used for neuroprotection of the fetus.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014).

Selection criteria: 

We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.

We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) 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 creatine.

Data collection and analysis: 

We identified no completed or ongoing randomised controlled trials.

Main results: 

We found no randomised controlled trials for inclusion in this review.

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