Abstract
While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid–base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity – actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn.
Highlights
The need for a therapy that reduces the probability of perinatal morbidity and mortality Two areas in obstetric and neonatal medicine that lack effective prophylactic treatments are premature birth and neonatal hypoxic-ischemic encephalopathy (HIE)
Notwithstanding the use of antenatal steroids and magnesium sulphate to lower the risk of hypoxia-induced brain injury at birth, there are currently no accepted treatments that are recommended for use during the 2nd and 3rd trimester of pregnancy for the purpose of preventing birth-related hypoxic-ischemic encephalopathy
By maintaining tissue energy levels and preventing oxidative stress, elevating tissue creatine levels by dietary supplementation is able to prevent tissue injury induced by hypoxia and circulatory collapse
Summary
The need for a therapy that reduces the probability of perinatal morbidity and mortality Two areas in obstetric and neonatal medicine that lack effective prophylactic treatments are premature birth and neonatal hypoxic-ischemic encephalopathy (HIE). Our studies showing the protective effects of this creatine treatment on brain structure [20], postnatal behaviour [83], diaphragm [18], and kidney structure and function [19] following asphyxial birth in the spiny mouse gives reason to think that creatine may benefit the preterm infants in their premature transition from fetal to newborn life. A multi-organ protectant against hypoxic injury in the neonate Our studies in the spiny mouse have shown that maternal dietary creatine supplementation prevents hypoxic injury to multiple organs including the brain [20], diaphragm [18], limb skeletal muscle (unpublished data) and kidney [19] at birth, increasing survival of the hypoxic term fetus, and improving postnatal growth [83]. Given that uterine activity in late gestation can be uncoordinated and labour sometimes ‘fail to progress’, a creatine supplementation program in pregnant women might decrease the caesarean section rate
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