title: Unmyelinated white matter loss in the preterm brain is associated with early increased levels of end-tidal carbon monoxide.
abstract: OBJECTIVE
  Increased levels of end-tidal carbon monoxide (ETCOc) in preterm infants during the first day of life are associated with oxidative stress, inflammatory processes and adverse neurodevelopmental outcome at 2 years of age. Therefore, we hypothesized that early ETCOc levels may also be associated with impaired growth of unmyelinated cerebral white matter.
  
  
  METHODS
  From a cohort of 156 extremely and very preterm infants in which ETCOc was determined within 24 h after birth, in 36 infants 3D-MRI was performed at term-equivalent age to assess cerebral tissue volumes of important brain regions.
  
  
  RESULTS
  Linear regression analysis between cerebral ventricular volume, unmyelinated white matter/total brain volume-, and cortical grey matter/total brain volume-ratio and ETCOc showed a positive, negative and positive correlation, respectively. Multivariable analyses showed that solely ETCOc was positively related to cerebral ventricular volume and cortical grey matter/total brain volume ratio, and that solely ETCOc was inversely related to the unmyelinated white matter/total brain volume ratio, suggesting that increased levels of ETCOc, associated with oxidative stress and inflammation, were related with impaired growth of unmyelinated white matter.
  
  
  CONCLUSIONS
  Increased values of ETCOc, measured within the first 24 hours of life may be indicative of oxidative stress and inflammation in the immediate perinatal period, resulting in impaired growth of the vulnerable unmyelinated white matter of the preterm brain.
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Cornelie A
authors.initials: CA
authors.lastname: Blok
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Karina J
authors.initials: KJ
authors.lastname: Kersbergen
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Niek E
authors.initials: NE
authors.lastname: van der Aa
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Britt J
authors.initials: BJ
authors.lastname: van Kooij
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Petronella
authors.initials: P
authors.lastname: Anbeek
authors.affiliation: Image Sciences Institute, University Medical Center, Utrecht, The Netherlands.
authors.forename: Ivana
authors.initials: I
authors.lastname: Isgum
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Linda S
authors.initials: LS
authors.lastname: de Vries
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Tannette G
authors.initials: TG
authors.lastname: Krediet
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Vreman
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Manon J
authors.initials: MJ
authors.lastname: Benders
mesh_terms: D000328:Adult; D002248:Carbon Monoxide / Q000378:metabolism*; D005260:Female; D006801:Humans; D007234:Infant, Premature / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D013997:Time Factors; D066127:White Matter / Q000473:pathology*
chemical_list: D002248:Carbon Monoxide