Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Dec;16(4):167-78.
doi: 10.1016/j.spen.2009.09.005.

The encephalopathy of prematurity--brain injury and impaired brain development inextricably intertwined

Joseph J Volpe  1
Affiliations
Review

The encephalopathy of prematurity--brain injury and impaired brain development inextricably intertwined

Joseph J Volpe. Semin Pediatr Neurol. 2009 Dec.

Abstract

The field of neonatal neurology, and specifically its focus on the premature infant, had its inception in neuropathologic studies. Since then, the development of advanced imaging techniques has guided our developing understanding of the etiology and nature of neonatal brain injury. This review promotes the concept that neonatal brain injury has serious and diverse effects on subsequent brain development, and that these effects likely are more important than simple tissue loss in determining neurologic outcome. Brain injury in the premature infant is best illustrative of this concept. This "encephalopathy of prematurity" is reviewed in the context of the remarkable array of developmental events actively proceeding during the last 16-20 weeks of human gestation. Recent insights into the brain abnormalities in survivors of preterm birth obtained by both advanced magnetic resonance imaging and neuropathologic techniques suggest that this encephalopathy is a complex amalgam of destructive and developmental disturbances. The interrelations between destructive and developmental mechanisms in the genesis of the encephalopathy are emphasized. In the future, advances in neonatal neurology will likely reiterate the dependence of this field on neuropathologic studies, including new cellular and molecular approaches in developmental neurobiology.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic diagram of cystic and noncystic periventricular leukomalacia (PVL). Coronal sections of cerebrum from a 28-week premature infant show focal necrotic and diffuse components of PVL. In cystic PVL (left) the focal necrotic lesions (circles) are macroscopic in size and evolve primarily to cysts, and in noncystic PVL, the focal necrotic lesions (dots) are microscopic in size and evolve primarily to glial scars. The diffuse component (yellow) is characterized by pre-OL injury, astrogliosis and microgliosis. Abbreviations: SVZ, subventricular zone; GE, ganglionic eminence; T, Thalamus; P, putamen; GP, globus pallidus. Reproduced with permission. (1)
Fig. 2
Fig. 2
Schematic diagrams of cerebrum (coronal sections) at 28 weeks' gestation depicting critical events in cerebral development. (A) Axons (green) emanate from thalamus (T) (projection fibers), corpus callosum (CC) (commissural fibers) and other cortical sites (association fibers) and synapse initially on subplate neurons (SPN). SPNs send axons to cortex to promote cortical development before the thalamo-cortical, commissural-cortical and cortico-cortical fibers enter the cortex. From cortex, axons (blue) descend to thalamus, basal ganglia and corticospinal (and corticopontine) tracts. Premyelinating oligodendrocytes (preOLs) (yellow) ensheath afferent and efferent axons before full differentiation to mature myelin-producing oligodendrocytes, especially after term. (B) The proliferation and migration of GABAergic interneurons from the dorsal telencephalic subventricular zone (SVZ) (blue) and the ventral germinative epithelium of the ganglionic eminence (GE) (green) are shown. Neurons from the SVZ (blue) migrate radially to the cortex, and those from the GE (green) tangentially and then radially to the cortex. The migrating stream of GABAergic interneurons (green) to the dorsal thalamus (T) also is shown. Other abbreviations: GP, globus pallidus; P, putamen. Reproduced with permission. (1)
Fig. 3
Fig. 3
Potential sequences of events leading to the major brain sequelae observed in premature infants with periventricular leukomalacia. The major sequelae include hypomyelination, and impaired cortical and thalamic development. For each sequence, the initiating primary injury is shown in yellow, and the subsequent secondary effects, shown in red boxes, are postulated to occur because of maturational/trophic/trans-synaptic disturbances, as described in the text. Abbreviations: Pre-OL, premyelinating oligodendrocyte; SPN, subplate neuron. Reproduced with permission. (1)
Fig. 4
Fig. 4
Schematic diagrams of coronal sections of cerebrum from a 28-week gestation premature infant depicting the anatomical relationships between the major developmental events and the topography of noncystic periventricular leukomalacia. For purposes of clarity the developmental events are separated (A and B). Abbreviations as in Figs. 1 and 2. Reproduced with permission. (1)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009;8(4):110–24. - PMC - PubMed
    1. Martin JA, Kung HC, Mathews TJ, Hoyert DL, Strobino DM, Guyer B, et al. Annual summary of vital statistics: 2006. Pediatrics. 2008;121(4):788–801. - PubMed
    1. Woodward LJ, Edgin JO, Thompson D, Inder TE. Object working memory deficits predicted by early brain injury and development in the preterm infant. Brain. 2005;128:2578–87. - PubMed
    1. Bayless S, Stevenson J. Executive functions in school-age children born very prematurely. Early Hum Dev. 2007;83(4):247–54. - PubMed
    1. Platt MJ, Cans C, Johnson A, Surman G, Topp M, Torrioli MG, 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;369(9555):43–50. - PubMed

Publication types