title: Caffeine for apnea of prematurity: Effects on the developing brain.
abstract: Caffeine is a methylxanthine that is widely used to treat apnea of prematurity (AOP). In preterm infants, caffeine reduces the duration of respiratory support, improves survival rates and lowers the incidence of cerebral palsy and cognitive delay. There is, however, little evidence relating to the immediate and long-term effects of caffeine on brain development, especially at the cellular and molecular levels. Experimental data are conflicting, with studies showing that caffeine can have either adverse or benefical effects in the developing brain. The aim of this article is to review current understanding of how caffeine ameliorates AOP, the cellular and molecular mechanisms by which caffeine exerts its effects and the effects of caffeine on brain development. A better knowledge of the effects of caffeine on the developing brain at the cellular and/or molecular level is essential in order to understand the basis for the impact of caffeine on postnatal outcome. The studies reviewed here suggest that while caffeine has respiratory benefits for preterm infants, it may have adverse molecular and cellular effects on the developing brain; indeed a majority of experimental studies suggest that regardless of dose or duration of administration, caffeine leads to detrimental changes within the developing brain. Thus there is an urgent need to assess the impact of caffeine, at a range of doses, on the structure and function of the developing brain in preclinical studies, particularly using clinically relevant animal models. Future studies should focus on determining the maximal dose of caffeine that is safe for the preterm brain.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Anzari
authors.initials: A
authors.lastname: Atik
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: De Matteo
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: Delphi
authors.initials: D
authors.lastname: Kondos-Devcic
authors.affiliation: Department of Neonatal Services, Royal Women's Hospital, Victorian Infant Brain Studies, Murdoch Children's Research Institute, and Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jeanie
authors.initials: J
authors.lastname: Cheong
authors.affiliation: Department of Neonatal Services, Royal Women's Hospital, Victorian Infant Brain Studies, Murdoch Children's Research Institute, and Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Lex W
authors.initials: LW
authors.lastname: Doyle
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia; The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia. Electronic address: mary.tolcos@rmit.edu.au.
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
mesh_terms: D000818:Animals; D001049:Apnea / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D002110:Caffeine / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D006801:Humans
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine
keywords: Adenosine; Apnea; Brain; Caffeine; Development; Prematurity