Anemia of Prematurity - Portal Neonatal

Pathophysiology:
Site of origin
The site of origin of PVH-IVH is the subependymal germinal matrix, a region of the developing brain
that regresses by term. During fetal development, the subependymal germinal matrix is a site of
neuronal proliferation as neuroblasts divide and migrate into the cerebral parenchyma. By
approximately 20 weeks' gestation, neuronal proliferation is completed; however, glial cell
proliferation is still ongoing. The germinal matrix supports the division of glioblasts and differentiation
of glial elements until approximately 32 weeks' gestation, at which time regression is nearly
complete. Cells of the germinal matrix are rich in mitochondria and, therefore, are quite sensitive to
ischemia.
Supplying this area of metabolically active differentiating cells is a primitive and fragile retelike
capillary network. Arterial supply to the plexus is through the Heubner artery and the lateral striate
arteries, which are within the distribution of the anterior and middle cerebral arteries, respectively.
This fragile capillary network is the site at which PVH-IVH hemorrhage occurs. Venous drainage is
through the terminal vein, which empties into the internal cerebral vein; this in turn empties into the
vein of Galen. At the site of confluence of the terminal vein and the internal cerebral vein, blood flow
direction changes from a generally anterior direction to a posterior direction.
Anatomic classification
PVH-IVH can be classified into 4 grades of severity. This classification, which is useful for prognostic
reasons when counseling parents and caregivers, is described in Table 1. Note that this
classification is based on radiological appearance rather than a pathophysiological description of
events leading to PVH-IVH.
Pathogenesis
Table 1. Classification of PVH-IVH
Grade Radiological Appearance – Site of Hemorrhage
I Subependymal region and/or germinal matrix
II
III
Subependymal hemorrhage with extension into lateral
ventricles without ventricular enlargement
Subependymal hemorrhage with extension into lateral
ventricles with ventricular enlargement
IV Intraparenchymal hemorrhage
PVH-IVH hemorrhage is now thought to be caused by capillary bleeding. Two major factors that
contribute to the development of PVH-IVH are (1) loss of cerebral autoregulation and (2) abrupt
alterations in cerebral blood flow and pressure. Most healthy infants who were born prematurely
have some ability to regulate cerebral blood flow through a process called autoregulation. However,
autoregulation is lost under some circumstances. Perlman and Volpe have demonstrated that the
alteration from autoregulation to a pressure-passive circulatory pattern appears to be an important
step in the development of PVH-IVH. When a pressure-passive circulatory pattern is challenged with
fluctuations of cerebral blood flow and pressure, hemorrhage can occur.
The autoregulatory abilities of neonates vary proportionally to gestational age at time of birth. The
range of perfusion pressures over which a premature neonate can control regional cerebral blood
flow is narrower and lower than that of infants born at term. In the absence of autoregulation, the
systemic blood pressure becomes the primary determinant of cerebral blood flow and pressure, a
pressure-passive situation.