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We offer the hypothesis that some forms of cerebral white matter damage (WMD) in preterm neonates might be caused by transplacental viral infection of the fetus during the first or second trimester of pregnancy. Potts and colleagues1 speculated on the possible role of a human pestivirus (PV) in the aetiology of congenital microcephaly. We suggest PV might be a candidate virus for some form of WMD. We further offer our view that a virus induced cytokine cascade might place the fetus at double jeopardy—that is, disturb white matter development and lead to preterm birth.
Virus related WMD
White matter damage is the most important predictor of childhood neuromotor disability among those born preterm. About 50% of infants who have echolucent zones in the periventricular white matter or ventriculomegaly on neonatal cranial ultrasound scans subsequently develop cerebral palsy.2 The multiple expressions of WMD, both on histological examination and neonatal cranial ultrasound scan, as focal, multifocal, or diffuse WMD,3 make multiple aetiologies likely. Some forms of WMD might be related to a hypoxic–ischaemic insult, but others might be associated with infection.
Four types of WMD can be distinguished on the basis of their location, histological patterns, and ultrasonographic appearance.3The first two forms comprise unifocal haemorrhagic infarctions, leading to periventricular echodensities on neonatal cranial ultrasound images, and multifocal necroses, leading to hypoechoic ultrasound images often described as “periventricular leucomalacia” (PVL). Current textbooks focus on fetal or newborn hypoxia–ischaemia as the pathogenesis of focal and multifocal forms of WMD.4 This is supported by studies showing that periventricular white matter damage can be induced by ligating the carotid arteries of mongrel …
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