title: Dietary interventions designed to protect the perinatal brain from hypoxic-ischemic encephalopathy--Creatine prophylaxis and the need for multi-organ protection.
abstract: Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth.
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Melbourne, Australia; Department of Obstetrics & Gynaecology, Monash University, Monash Medical Centre, Clayton, Melbourne, Australia. Electronic address: stacey.ellery@hudson.org.au.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Ellery
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Melbourne, Australia; Department of Obstetrics & Gynaecology, Monash University, Monash Medical Centre, Clayton, Melbourne, Australia.
authors.forename: Hayley
authors.initials: H
authors.lastname: Dickinson
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: McKenzie
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Melbourne, Australia; Department of Obstetrics & Gynaecology, Monash University, Monash Medical Centre, Clayton, Melbourne, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Walker
mesh_terms: D000818:Animals; D001238:Asphyxia Neonatorum / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003401:Creatine / Q000008:administration & dosage* / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007231:Infant, Newborn; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009102:Multiple Organ Failure / Q000378:metabolism / Q000517:prevention & control; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011247:Pregnancy
chemical_list: D003401:Creatine
keywords: Birth asphyxia; Fetal development; Nutrition; Pregnancy; Spiny mouse