Chapter 56: Germinal Matrix Hemorrhage

SCOPE

DISEASE/CONDITION(S)

Periventricular-intraventricular hemorrhage (PIVH) in preterm infants.

GUIDELINE OBJECTIVE(S)

Review the frequency, classification, pathogenesis, and sequelae of germinal matrix hemorrhage in preterm infants. List methods of prevention and management, including screening.

BRIEF BACKGROUND

PIVH remains a significant cause of morbidity among premature neonates. While the incidence of intraventricular hemorrhage (IVH) has declined since the 1970s, the total number of cases has not changed over the past few decades due to increased survival of neonates at progressively earlier gestational ages. IVH occurs in approximately 20% of neonates born <1500 g.

PIVH originates from the subependymal germinal matrix, a highly vascular structure surrounding the entire lateral ventricle but most apparent in the sagittal plane near the caudate nucleus. Proliferating neuronal and glial cells migrate outward from the germinal matrix toward the cortex; thus disruption of these structures from PIVH can lead to neurodevelopmental impairment.

Predisposition for PIVH: Review of Germinal Matrix Structure

Multiple critical protective structural elements are reduced in the germinal matrix vessels as compared to normal capillaries elsewhere in the body due to the high rate of angiogenesis and endothelial cell turnover. Protective pericytes which strengthen the vessels and produce extracellular matrix are reduced. The germinal matrix basal lamina in neonates is deficient in fibronectin compared to white and grey matter areas. Studies of fibronectin knockout animal models have shown propensity for cerebral hemorrhage, and it is hypothesized that a similar connection exists in human neonates. Astrocyte processes (end-feet) also comprise a proportion of the blood-brain barrier by wrapping around the blood vessels. In premature neonates these end-feet are deficient in glial fibrillary acidic protein (GFAP), a key component of the supportive cytoskeleton. The combination of reduced pericytes, basal lamina fibronectin, and astrocyte GFAP render the germinal matrix endothelium highly susceptible to hemorrhage.

Classification

PIVH is classified into four categories (Table 56.1). If ventricular dilation is noted on cranial ultrasound it must be carefully reviewed to determine if dilation is secondary to an acute filling and distention by blood products (grade 3) or due to post-hemorrhagic hydrocephalus. In addition, in the past, grade 4 PIVH was incorrectly thought to be an extension of hemorrhage from the lateral ventricles into surrounding periventricular white matter. As blood accumulates in the ventricles, there is progressive compression of the surrounding venous drainage, resulting in obstruction and secondary venous infarction. Therefore, grade 4 PIVH has been more appropriately renamed periventricular hemorrhagic infarction (PVHI).