Unmyelinated White Matter Loss in the Preterm Brain Is Associated with Early Increased Levels of End-Tidal Carbon Monoxide

Cornelie A Blok,Linda S De Vries,Hendrik J Vreman,Karina J Kersbergen,Tannette G Krediet,Niek E Van Der Aa,Britt J Van Kooij,Petronella Anbeek,Floris Groenendaal,Frank Van Bel,Manon J Benders,Ivana Isgum,James A Duce

doi:10.1371/journal.pone.0089061

Cornelie A Blok, Linda S De Vries + Show 11 more

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https://doi.org/10.1371/journal.pone.0089061

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Journal: PloS one	Publication Date: Mar 12, 2014
Citations: 30	License type: CC BY 4.0

Affiliation: Wilhelmina Children's Hospital, Stanford University

Abstract

ObjectiveIncreased 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.MethodsFrom 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.ResultsLinear 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.ConclusionIncreased 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.

Highlights

Carbon monoxide (CO), a product of oxidative degradation of heme, diffuses from the vascular compartment to alveolar air, where it can be quantitated in exhaled air as end-tidal CO (ETCOc) [1]
In preterm infants with severe respiratory distress syndrome subsequently developing bronchopulmonary dysplasia (BPD) and in infants of preeclamptic mothers with HELLP syndrome we found an association between elevated ETCOc and oxidative stress and inflammation using malondialdehyde and pro-inflammatory cytokines as markers [4,5]
In a recent study in preterm infants we reported a relation between elevated ETCOc levels during the first 24 hours of life and adverse neurodevelopmental outcome at 3.5 years of age [12]

Summary

Introduction

Carbon monoxide (CO), a product of oxidative degradation of heme, diffuses from the vascular compartment to alveolar air, where it can be quantitated in exhaled air as end-tidal CO (ETCOc) [1]. In preterm infants with severe respiratory distress syndrome subsequently developing bronchopulmonary dysplasia (BPD) and in infants of preeclamptic mothers with HELLP syndrome we found an association between elevated ETCOc and oxidative stress and inflammation using malondialdehyde and pro-inflammatory cytokines as markers [4,5]. In up to 50% of extremely and very preterm infants (subtle) white matter damage (WMD) is the most important cause of neuronal-axonal disease with subsequent adverse cognitive, behavioral and neuromotor outcome [4]. WMD is characterized by a marked decrease in immature oligodendrocytes, which are extremely sensitive to reactive oxygen and nitrogen species and pro-inflammatory cytokines, leading to inadequate myelinization and white matter axon formation [10,11]. In a recent study in preterm infants we reported a relation between elevated ETCOc levels during the first 24 hours of life and adverse neurodevelopmental outcome at 3.5 years of age [12]

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Conclusion