Neonatal white matter injury

Thiviya Selvanathan MD (

Dr. Selvanathan of the Hospital for Sick Children and University of Toronto has no financial relationships to disclose.

Steven P Miller MDCM MAS FRCPC (

Dr. Miller of the Hospital for Sick Children and University of Toronto has no financial relationships to disclose.

Vann Chau MD FRCPC (

Dr. Chau of the Hospital for Sick Children and University of Toronto has no financial relationships to disclose.

Michael V Johnston MD, editor. (

Dr. Johnston of Johns Hopkins University School of Medicine has no relevant financial relationships to disclose.

Originally released April 6, 1994; last updated November 10, 2020; expires November 10, 2023


Neonatal white matter injury, formerly called periventricular leukomalacia, is the leading cause of cerebral palsy and other neurocognitive deficits in preterm-born children. White matter injury occurs primarily in preterm infants born before 32 weeks' gestation. White matter injury is almost as common in term neonates with congenital heart disease, given delays in prenatal brain maturation secondary to in utero hypoxia (Miller et al 2007; Sun et al 2015). White matter injury is seen less commonly in full-term neonates with hypoxic-ischemic encephalopathy, especially in the younger gestational age range of “full-term.” This article reviews white matter injury in infants born preterm. Advances in neuroimaging and epidemiological studies have increased our insight into the pathophysiology of this condition. Although no cure currently exists, several clinical trials are ongoing with the aim to prevent disease or to improve long-term outcomes. This article provides a comprehensive review of the clinical, pathological, and imaging aspects of neonatal white matter injury, and they discuss advances in research relevant to this condition. A case study involving a preterm infant is reviewed, including maternal history, obstetrical history, and patient's NICU hospital course; the study demonstrates long-term outcomes that may be associated with neonatal white matter injury.

Key points


• White matter injury is the result of the selective vulnerability of pre-oligodendrocytes in the preterm brain to hypoxia-ischemia. This vulnerability may be potentiated by inflammation.


• White matter injury is a key modifiable risk factor for adverse neurodevelopmental outcomes in preterm infants born earlier than 32 weeks' gestation.


• With advances in neonatal intensive care, there has been a shift from more severe cystic white matter injury to milder diffuse non-cystic white matter injury, which is associated with a decrease in the prevalence of cerebral palsy but an increase in behavioral and cognitive deficits observed in children born preterm.


• Serial neuroimaging with head ultrasound or MRI is critical in identifying cystic and non-cystic white matter injury in preterm infants due to the evolution of neuroimaging findings over time.


• White matter injury severity and location are predictors of adverse neurodevelopmental outcomes.

Historical note and terminology

The first description of neonatal white matter injury comes from Parrot, in which he described pale infarcts seen as yellowish or chalky plaques in the lateral corners of the periventricular white matter; softening of the plaques formed cavities, which did not communicate with the ventricles (Parrot 1868). Fifty years later, Schwartz re-described these lesions, but it was not until the early 1960s that Banker and Larroche named this lesion “periventricular leukomalacia” and described its clinical pathological correlations with immature and mature infants, hypoxia-ischemia, and spastic cerebral palsy (Banker and Larroche 1962). Later, Leviton and Gilles used the term “perinatal telencephalic leuco-encephalopathy” (Leviton and Gilles 1973). Banker and Larroche described neonatal white matter injury as periventricular cystic focal necrosis with loss of all cellular elements, surrounded by a diffuse, non-necrotic injury to the periventricular white matter, which was the predominant subtype of white matter injury seen in preterm infants at the time.

With advances in neonatal intensive care, diffuse non-cystic white matter injury has become the more prevalent form of white matter injury seen in preterm infants. It is associated with punctate white matter lesions seen on MRI and abnormal white matter microstructure and maturation. Volpe coined the term “encephalopathy of prematurity” to describe the gray matter dysmaturation that accompanies diffuse white matter injury (Volpe 2009). These changes contribute to cognitive and behavioral abnormalities seen in contemporary cohorts of preterm infants, even in the absence of motor impairments (Schneider and Miller 2019).

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