The Encephalopathy of Prematurity—Brain Injury and Impaired Brain Development Inextricably Intertwined
Section snippets
Personal Perspective
This presentation will focus on the brain of the premature infant. My interest in premature infants began in the early 1970s when neonatal intensive care began its ascendancy to the highly accomplished medical discipline of today. I was inspired by the seminal neuropathologic studies of Betty Banker, Jeanne-Claudie Larroche, E. Pierson Richardson, Gilles Lyon, Dawna Armstrong, Lucy Rorke, Floyd Gilles, Jonathan Wigglesworth, and my colleague of the past 20 years, Hannah Kinney. My review of the
Neuropathology—Encephalopathy of Prematurity
The neuropathology of encephalopathy of prematurity consists of PVL and the often-associated neuronal/axonal disease. These 2 aspects are discussed briefly next.
Major Developmental Events in Human Brain During the Premature Period
The encephalopathy of prematurity, that is, both PVL and the associated neuronal/axonal disease, occurs during a period of extraordinarily rapid and complex events in human brain development.1, 10 The developmental events between 24 and 40 weeks involve, particularly (1) in cerebral white matter—pre-OLs, axons, microglia, and neurons (subplate and late migrating GABAergic neurons); (2) two proliferative zones—the dorsal cerebral subventricular zone (SVZ) and the ventral germinative epithelium
Encephalopathy of Prematurity—Combination of Destructive and Developmental Disturbances
As noted in the Introduction, the hypothesis of this review is that the encephalopathy of prematurity, that is, the combination of PVL and neuronal/axonal disease described under Neuropathology, is a complex amalgam of primary destructive and secondary developmental disturbances.1 The developmental disturbances include impaired cell–cell interactions, involving intercellular trophic support, retrograde effects (“dying back”), and anterograde effects (eg, Wallerian degeneration, trans-synaptic
Conclusions
It is unclear which of the 5 potential scenarios depicted in Figure 3 is most important in the encephalopathy of prematurity. Pre-OL injury may be the most common starting point. However, it seems likely that more than one and perhaps all the scenarios shown in Figure 3 operate to a varying extent.1 Determinants of the relative importance of each scenario could relate to factors such as the gestational age of the infant, the timing and nature of the insult(s), critical associated factors such
References (165)
Brain injury in premature infants: A complex amalgam of destructive and developmental disturbances
Lancet Neurol
(2009)- et al.
Executive functions in school-age children born very prematurely
Early Hum Dev
(2007) - et al.
Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born prematurely (<32 weeks) in 16 European centres: A database study
Lancet
(2007) - et al.
Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): A longitudinal cohort study
Lancet
(2008) - et al.
Positive screening results on the modified checklist for autism in toddlers: Implications for very preterm populations
J Pediatr
(2009) - et al.
White matter damage and intraventricular hemorrhage in very preterm infants: The EPIPAGE study
J Pediatr
(2003) - et al.
Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome
J Pediatr
(2005) - et al.
Sex differences in cerebral volumes of 8-year-olds born preterm
J Pediatr
(2004) - et al.
Volumetric analysis of regional cerebral development in preterm children
Pediatr Neurol
(2004) - et al.
Changes in white matter diffusion anisotropy in adolescents born prematurely
NeuroImage
(2006)
Glial responses to neonatal hypoxic-ischemic injury in the rat cerebral cortex
Int J Dev Neurosci
Magnetic resonance imaging of the brain in a cohort of extremely preterm infants
J Pediatr
Defining the nature of the cerebral abnormalities in the premature infant—a qualitative magnetic resonance imaging study
J Pediatr
Expression of b-amyloid precursor protein in axons of periventricular leukomalacia brains
Pediatr Neurol
Characteristic neuropathology of leukomalacia in extremely low birth weight infants
Pediatr Neurol
Early detection of axonal and neuronal lesions in prenatal-onset periventricular leukomalacia
Brain Dev
Periventricular leukomalacia: relation to gestational age and axonal injury
Pediatr Neurol
Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants
NeuroImage
Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography
NeuroImage
Abnormal deep grey matter development following preterm birth detected using deformation based morphometry
NeuroImage
Vulnerability of developing brainI. Some lasting effects of x-irradiation
Exp Neurol
A new alamar blue viability assay to rapidly quantify oligodendrocyte death
J Neurosci Methods
Human oligodendroglial development: Relationship to periventricular leukomalacia
Semin Pediatr Neurol
Neurotransmitter receptors in the life and death of oligodendrocytes
Neuroscience
Molecular insights on the cerebral innate immune system
Brain Behav Immun
Annual summary of vital statistics: 2006
Pediatrics
Object working memory deficits predicted by early brain injury and development in the preterm infant
Brain
Outcomes of extremely low birth weight (<1 kg) and extremely low gestational age (<28 weeks) infants with bronchopulmonary dysplasia: Effects of practice changes in 2000 to 2003
Pediatrics
Cognitive maturation in preterm and term born adolescents
J Neurol Neurosurg Psychiatr
Positive screening for autism in ex-preterm infants: Prevalence and risk factors
Pediatrics
Neurology of the Newborn, 5th ed
Early working memory in children born with extremely low birth weight: Assessed by object permanence
J Child Neurol
Positive screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in extremely low gestational age newborns
J Pediatr
Motor and executive function at 6 years of age after extremely preterm birth
Pediatrics
The EPICure study: Associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth
Arch Dis Child
Specific language difficulties and school achievement in children born at 25 weeks of gestation or less
J Pediatr
Encephalopathy of prematurity includes neuronal abnormalities
Pediatrics
Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings
AJNR Am J Neuroradiol
Abnormal cerebral structure is present at term in premature infants
Pediatrics
Neonatal MRI to predict neurodevelopmental outcomes in preterm infants
N Engl J Med
Nitrosative and oxidative injury to premyelinating oligodendrocytes is accompanied by microglial activation in periventricular leukomalacia in the human premature infant
J Neuropathol Exp Neurol
Selective vulnerability of preterm white matter to oxidative damage defined by F(2)-isoprostanes
Ann Neurol
Neonatal loss of gamma-aminobutyric acid pathway expression after human perinatal brain injury
J Neurosurg
Myelin abnormalities without oligodendrocyte loss in periventricular leukomalacia
Brain Pathol
Regional brain volume abnormalities and long-term cognitive outcome in preterm infants
JAMA
Adolescents who were born very preterm have decreased brain volumes
Brain
Effects of very low birthweight on brain structure in adulthood
Dev Med Child Neurol
Brain volumes in adult survivors of very low birth weight: A sibling-controlled study
Pediatrics
Structural and functional brain developmental after hydrocortisone treatment for neonatal chronic lung disease
Pediatrics
Abnormal white matter signal on MR imaging is related to abnormal tissue microstructure
AJNR Am J Neuroradiol
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This work was supported by the NINDS, Grant Number P01-NS038475.