Anemia of Prematurity - Portal Neonatal

Pathogenesis of sequelae
The major sequelae of PVH-IVH relate to the destruction of cerebral parenchyma and the
development of posthemorrhagic hydrocephalus. Furthermore, the sequelae of ventricular-peritoneal
shunt placement (primarily infection) can contribute to poor neurodevelopmental outcomes.
Following parenchymal hemorrhages, necrotic areas form cysts that can become contiguous with
the ventricles (porencephalic cysts). Cerebral palsy is the primary neurological disorder observed
after PVH-IVH, though mental retardation and seizures can ensue as well. The occurrence of
cerebral palsy is related to the anatomical structure of the periventricular region of the brain. The
cortical spinal motor tracts run in this region. The white matter is arranged such that tracts
innervating the lower extremities are nearest to the ventricles, followed by those innervating the
trunk, the arm, and, finally, the face. This anatomical arrangement accounts for the greater degree of
motor dysfunction of the extremities as compared to the face (spastic hemiplegia in unilateral lesions
and spastic diplegia or quadriplegia in bilateral lesions). In addition to destruction of periventricular
motor tracts, destruction of the germinal matrix itself can occur. The long-term effects of the loss of
glial cell precursorsare unknown.
The second mechanism by which long-term neurological outcome can be altered is through the
development of posthemorrhagic hydrocephalus. The mechanisms by which hydrocephalus develop
include (1) decreased absorption of cerebral spinal fluid (CSF) secondary to obstruction of arachnoid
villi by blood and debris or the development of obliterative arachnoiditis (ie, communicating
hydrocephalus) and (2) obstruction to CSF circulation (ie, obstructive hydrocephalus).
Finally, because the development of PVH-IVH is related to alterations in cerebral blood flow, injury to
other portions of the brain must be considered. Two disorders that may coexist with PVH-IVH are
global hypoxic-ischemic injury and periventricular leukomalacia (PVL). PVL is a disorder of the
periventricular white matter, similar to periventricular hemorrhagic infarction. However, the
mechanism of PVL, nonhemorrhagic ischemic necrosis, differs substantially from that of all grades of
PVH-IVH, including periventricular hemorrhagic infarction. Both PVL and global hypoxic-ischemic
injury can significantly affect the neurologic outcome in infants affected with these disorders.
The significance of alterations in cerebral blood flow is perhaps of greater importance than
previously recognized, not only in the generation of hemorrhage but in more diffuse brain injury as
well. For example, numerous studies have demonstrated alterations in cerebral blood flow during
rapid infusions of indomethacin, raising concern that prophylactic use might improve the risk of PVH-
IVH while increasing the risk of periventricular leukomalacia. Fortunately, this has not been shown to
be true. Indeed, in a large follow-up study of patients receiving indomethacin prophylaxis, Ment
demonstrated that while indomethacin prophylaxis did not result in improved motor outcomes,
cognitive and verbal outcomes were improved with prophylaxis. The pathophysiology described
above might appear inconsistent with that observation; however poorly understood alterations in
cerebral blood flow distribution and cellular energy utilization might beneficially be effected by
indomethacin.
Frequency:
• In the US: Incidence of PVH-IVH in infants of very low birth weight (