About twelve thousand premature infants develop intraventricular hemorrhage (IVH) every year in the United States alone (1
). The incidence of IVH in very low birth weight infants (<1500g) has declined from 40–50% in the early 1980s to 20% in the late 1980s (3
). However, in the last two decades the occurrence of IVH has remained stationary (4
). In extremely premature infants weighing 500–750g, IVH occurs in about 45% of neonates (5
). Thus, IVH continues to be a major problem of premature infant in modern neonatal intensive care units worldwide.
IVH characteristically initiates in the periventricular germinal matrix. The germinal matrix, located on the head of caudate nucleus and underneath ventricular ependyma, is a highly vascular collection of glial and neuronal precursor cells (). This periventricular region is selectively vulnerable to hemorrhage in premature infants predominantly in the first 48 h of life. When the hemorrhage in the germinal matrix is substantial, the ependyma breaks, and the cerebral ventricle fills up with blood. Thus, IVH is typically a progression of germinal matrix hemorrhage. Majority of these infants are asymptomatic and the diagnosis is based on screening cranial ultrasound. Some infants manifest with subtle abnormalities in the level of consciousness, movement, tone, respiration and eye movement; and uncommonly, there is a catastrophic deterioration presenting with stupor, coma, decerebrate posturing, generalized tonic seizure, and quadriparesis.
IVH reduces the survival of premature infants and enhances the risk of a number of neurological sequelae. A higher mortality rate in premature infants with severe IVH has been reported compared to infants without IVH (6
). Premature infants with moderate to severe IVH (grade 3–4) are at high risk of post-hemorrhagic hydrocephalus, cerebral palsy and mental retardation, while infants with mild IVH (grade 1–2) are at risk of developmental disabilities (7
). About 45–85% of premature infants with moderate-to-severe IVH develop major cognitive deficits and approximately 75% of these infants need special education in school (9
). A recent study has shown better functional outcome of surviving preterm infants with perventricular hemorrhagic infarction at school age than previously thought (10
Pathogenesis of IVH is multifactorial and is primarily ascribed to a) inherent fragility of the germinal matrix vasculature, b) disturbance in the cerebral blood flow (CBF) and c) platelet and coagulation disorders. A number of risk factors including vaginal delivery, low Apgar score, severe respiratory distress syndrome, pneumothorax, hypoxia, hypercapnia, seizures, patent ductus arteriosus, thrombocytopenia, infection, and others predispose to the development of IVH () (11
). These risk factors appear to induce IVH primarily by disturbing the cerebral blood flow. However, thrombocytopenia contributes to IVH by causing hemostatic failure.
Neonatal risk factors in the pathogenesis of IVH.