Elsevier

Early Human Development

Volume 53, Issue 2, 1 December 1998, Pages 99-120
Early Human Development

White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome

https://doi.org/10.1016/S0378-3782(98)00037-1Get rights and content

Abstract

Periventricular white matter injury, specifically cystic periventricular leukomalacia (PVL) and ipsilateral hemorrhage into white matter associated with periventricular-intraventricular hemorrhage (PV-IVH), contribute significantly to neonatal mortality and long-term neurodevelopmental deficits in the premature infant. The first lesion PVL occurs in approximately 3–4% of infants of birth weight (BW) <1500 grams. It manifests either as a focal or diffuse lesion within white matter. Although the pathogenesis of PVL is complex and likely multifactorial, principle contributors include vascular factors which markedly increase the risk for ischemia during periods of systemic hypotension and the intrinsic vulnerability of the oligodendrocyte to neurotoxic factors such as free radicals or cytokines. Clinical associations with PVL include a history of chorioamnionitis, prolonged rupture of membranes, asphyxia, sepsis, hypocarbia, etc. The vast majority of infants exhibit long-term neurodevelopmental deficits that affect motor, cognitive and visual function. The second lesion, the ipsilateral hemorrhage into white matter lesion associated with PV-IVH, occurs in approximately 10–15% of infants of BW <1000 grams. The white matter injury appears to be a venous infarction with hemorrhage occurring as a secondary phenomenon. Prevention of this lesion has to include prevention of the associated PV-IVH. In this regard, the antenatal administration of glucocorticoids has been associated with a significant reduction in the sonographic incidence of severe IVH and the associated white matter involvement. The postnatal administration of indomethacin to high risk infants appears to hold the most promise at the current time in preventing this lesion. The neurodevelopmental outcome with extensive white matter injury is universally poor, affecting long-term motor and cognitive deficits; the long-term outcome is more favorable with lesser involvement. A clearer understanding of pathogenesis of both conditions is essential so as to provide targeted preventative strategies.

Section snippets

Background

Injury to periventricular white matter represents the most significant problem contributing to neonatal mortality as well as long-term neurologic deficits in the premature infant. Two lesions account for the majority of white matter injury in the premature infant, namely cystic periventricular leukomalacia (PVL) and intraparenchymal white matter hemorrhage associated with periventricular–intraventricular hemorrhage (PV–IVH). 1, 2Cranial ultrasonography has been pivotal in defining the magnitude

Background

PVL refers to necrosis of white matter adjacent to the external angles of the lateral ventricles and is regarded as the principal ischemic lesion of the premature infant [3]. The incidence of PVL has ranged from 4–15% (see Refs. 3, 4for review). Part of this wide variation in incidence relates to the sonographic definition used by various authors to describe the condition. Most reports frequently include infants with IVH, and the ipsilateral intraparenchymal hemorrhage and transient hyperechoic

Background

PV–IVH is the most common serious neurologic lesion of the neonatal period occurring predominantly in the premature infant. Although the incidence of PV–IVH appears to be declining, the occurrence of severe IVH alone or with associated intraparenchymal involvement remains a significant problem particularly in the very low birthweight infant <1000 g birthweight 1, 72, 73(Table 2). Thus, the unilateral involvement of white matter commonly referred to as an intraparenchymal echogenicity (IPE) or

Conclusions

Injury to periventricular white matter remains a significant problem affecting approximately 15–20% of extremely premature infants. The outcome following such injury is invariably unfavorable with motor as well as cognitive impairment. A clearer understanding of pathogenesis is critical in order to provide targeted interventions to those infants at highest risk.

References (134)

  • B.H Yoon et al.

    High expression of tumor necrosis factor ∝ and interleukin 6 in periventricular leukomalacia

    Am J Obstet Gynecol

    (1997)
  • J.K Relton et al.

    Interleukin-I receptor antagonism inhibits ischemic and excitotoxic neuronal damage in the rat

    Brain Res Bull

    (1992)
  • R Bejar et al.

    Antenatal origin of neurologic damage in newborn infants. I. Preterm infants

    Am J Obstet Gynecol

    (1988)
  • S.D Dixon et al.

    Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates

    J Pediatr

    (1989)
  • R Mirro et al.

    Relationship between mean airway pressure, cardiac output and organ blood flow with normal and decreased respiratory compliance

    J Pediatr

    (1987)
  • L De Vries et al.

    Evaluation of periventricular leukomalacia during the neonatal period and infancy: correlation of imaging and postmortem findings

    Early Hum Dev

    (1988)
  • J Goddard-Finegold et al.

    Intraventricular hemorrhage following volume expansion after hypovolemic hypotension in the newborn beagle

    J Pediatr

    (1982)
  • R.N Goldberg et al.

    The associations of rapid volume expansion and intraventricular hemorrhage in the preterm infant

    J Pediatr

    (1980)
  • H.S Bada et al.

    Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage

    J Pediatr

    (1990)
  • J.M Perlman et al.

    Relationship of uric acid concentrations and severe intraventricular hemorrhage/leukomalacia in the premature infant

    J Pediatr

    (1998)
  • T.J Garite et al.

    A randomized placebo controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24–28 weeks gestation

    Am J Obstet Gynecol

    (1992)
  • A.H Jobe et al.

    Beneficial effects of combined use of prenatal steroids and postnatal surfactant on preterm infants

    Am J Obstet Gynecol

    (1993)
  • J.E Maher et al.

    March of Dimes Multicenter Study Group. The effect of glucocorticoid therapy in the very premature infant

    Am J Obstet Gynecol

    (1994)
  • L.L Wright et al.

    Evidence from multicenter networks on the current use and effectiveness of antenatal corticosteroids in low birthweight infants

    Am J Obstet Gynecol

    (1995)
  • J.M Perlman et al.

    Relationship between periventricular intraparenchymal echodensities and germinal matrix-intraventricular hemorrhage in the very low birth weight neonate

    Pediatrics

    (1993)
  • J.M Perlman et al.

    Bilateral cystic periventricular leukomalacia in the premature infant: associated risk factors

    Pediatrics

    (1996)
  • Volpe JJ. Neurology of the newborn. third edition. Philadelphia, PA: Saunders,...
  • L.S De Vries et al.

    Perinatal risk factors for the development of extensive cystic leukomalacia

    Am J Dis Child

    (1988)
  • L.S De Vries et al.

    Late onset cystic leukomalacia

    Arch Dis Child

    (1986)
  • B.Q Banker et al.

    Periventricular leukomalacia of infancy: a form of neonatal anoxic encephalopathy

    Arch Neurol

    (1962)
  • J De Reuck et al.

    Pathogenesis and evolution of periventricular leukomalacia in infancy

    Arch Neurol

    (1972)
  • D Armstrong et al.

    Periventricular leukomalacia in neonates: complications and sequelae

    Arch Dis Child

    (1974)
  • J De Reuck

    The human periventricular arterial blood supply and the anatomy of cerebral infarctions

    Eur Neurol

    (1971)
  • S Takashima et al.

    Development of cerebrovascular architecture and its relationship to periventricular leukomalacia

    Arch Neurol

    (1978)
  • J De Reuck

    Cerebral angioarchitecture and perinatal brain lesions in premature and full term infants

    Acta Neurol Scand

    (1984)
  • L.B Rorke

    Anatomic features of the developing brain implicated to hypoxic–ischemic injury

    Brain Pathol

    (1992)
  • Larroche JC. Developmental pathology of the neonate. New York: Raven Press,...
  • M Cavazzutti et al.

    Regulation of local cerebral blood flow in normal and hypoxic newborn dogs

    Ann Neurol

    (1982)
  • W Szymonowicz et al.

    Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near term and term lamb

    Pediatr Res

    (1990)
  • R.S.K Young et al.

    Selective reduction of blood flow to white matter during hypotension in newborn dogs: a possible mechanism of periventricular leukomalacia

    Ann Neurol

    (1982)
  • C.H Lou et al.

    Impaired autoregulation of cerebral blood flow in the distressed newborn infant

    J Pediatr

    (1979)
  • R.G Faix et al.

    Association of septic shock caused by early onset Group B streptococcal sepsis and periventricular leukomalacia in the preterm infant

    Pediatrics

    (1985)
  • V.M Miall-Allen et al.

    Mean arterial blood pressure and neonatal cerebral lesions

    Arch Dis Child

    (1987)
  • G Greisen et al.

    Severe hypocarbia in preterm infants and neurodevelopmental deficit

    Acta Paediatr Scand

    (1986)
  • S Fujimoto et al.

    Hypocarbia and cystic periventricular leukomalacia in premature infants

    Arch Dis Child

    (1994)
  • T.E Wiswell et al.

    Effects of hypocarbia on the development of cystic periventricular leukomalacia in premature infants treated with high frequency jet ventilation

    Pediatrics

    (1996)
  • J.M Perlman et al.

    Episodes of apnea and bradycardia in the preterm newborn: impact on cerebral circulation

    Pediatrics

    (1985)
  • J.E Rice et al.

    The influence of immaturity on hypoxic–ischemic brain damage in the rat

    Ann Neurol

    (1981)
  • A Oka et al.

    Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms and prevention

    J Neurosci

    (1993)
  • A Leviton et al.

    Acquired perinatal leukoencephalopathy

    Ann Neurol

    (1984)
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