Periventricular-Intraventricular hemorrhage is a disease process that primarily affects the premature newborn infant. Hemorrhage occurs when vessels of the germinal matrix in the periventricular area rupture, which then extends into the intraventricular space. In severe cases, bleeding will occupy a significant portion of the ventricle (intraventricular hemorrhage) and extend into the intraparenchymal space adjacent to the ventricle (periventricular hemorrhage). Infants most at risk are those born prior to 33 weeks gestational age as after this time the germinal matrix involutes. This is a graded disease process, and the more severe bleeding intuitively leads to more long-term deficits, up to and including death.
The predominate etiology of periventricular and intraventricular hemorrhage is suspected to be due to the thin fragility of the vessels in the germinal matrix and an immature cerebral autoregulation mechanism in the preterm neonate.
Blood vessel morphology in the germinal matrix of the neonate differs from that in other cortical areas mainly due to the increased metabolic demand required by the rapid turnover of precursor cells in this region. Blood vessels supplying the germinal matrix have a higher density and area than other cortical regions. In addition to this, the vessel morphology differs, mainly in that vessels supplying the germinal matrix are more round versus flat in other cortical regions, due to a level of vessel immaturity.
Damage to the surrounding white matter tissues from intraventricular hemorrhage has several theorized mechanisms, primarily compression from ventricular dilation and direct white matter tissue trauma from the weakened ependymal lining. Compression on the adjacent white matter from dilated ventricles has been shown in non-human models to show axonal damage, white matter edema, and various reactive cellular components. A similar mechanism is present when the ependymal lining stretches (an otherwise intact structure protecting white matter from exposure to ventricular contents) and undergoes violation with IVH, blood products, and other reactive cellular components are exposed directly to white matter.
The incidence of periventricular hemorrhage varies based on gestational age and birth weight. Generally, the incidence has decreased since the 1980s. The overall incidence for all neonates of 22 to 28 weeks gestational age is 32%. Further delineating based on weight, IVH occurs in 25 to 30% of neonates less than 1500g and occurs in up to 45% of neonates less than 1000g. There is a 3.5% decrease in disease for each week of additional gestation age up to 32 weeks.
In the developing brain of the premature infant, there is a considerable lack of supportive tissue surrounding the germinal matrix. Bleeding in the periventricular space typically occurs in the germinal matrix and is as a result of weak capillaries that will spontaneously rupture, this may be due to stress on the infant in the form of hypoxia. When studied, infants with higher degrees of fluctuation in cerebral blood flow, potentially placing increased stress on capillary walls, have a higher incidence of intraventricular hemorrhage.
In severe germinal matrix bleeding due to the immature nature of the infant neurologic structures, the ependymal layer will become disrupted, and the germinal matrix bleeding will proceed into the ventricle.
There are several histologic structures that in prematurity place a preterm infant at an increased risk of intraventricular hemorrhage. These primarily support structures make up the blood-brain barrier in the germinal matrix. They include:
Historical features that will predispose an infant to intraventricular hemorrhage primarily result from the course of the pregnancy of the mother. These include:
Specific details from the birth of the infant may also increase the likelihood of intraventricular hemorrhage in the preterm infant, these include:
Primary diagnosis of intraventricular hemorrhage is via the use of transcranial ultrasound doppler screening in all neonates less than 30 weeks gestational age. This is the recommendation established by the American Academy of Neurology and suggests the initial ultrasound should take place between 7 and 14 days of life with a repeat ultrasound at between 36 and 40 weeks maturity.
Although not routinely employed in the initial evaluation, MRI has been demonstrated to be effective in identifying cerebellar hemorrhages and white matter injury.
The degree of bleeding is based on U/S findings which had traditionally been graded 1 through 4 but has recently undergone revision to the following:
The primary treatment strategy should be aimed at the prevention of preterm birth if possible. This should include the routine administration of antenatal steroids if preterm birth is the expectation and transfer of the mother to a facility that has advanced capabilities of caring for very low birth weight infants before delivery.
In the delivery of the preterm infant delayed cord clamping should be the routine practice. This method has support from the American College of Obstetricians and Gynecologists, and a delay of between 30 and 180 seconds has demonstrated a reduced risk (RR 0.59) of intraventricular hemorrhage compared to the immediate clamping group.
Postnatal management should be targeted to limit hypoxia and fluctuations in cerebral blood flow. Several pharmacologic agents have been utilized to achieve those goals and include:
The differential diagnosis for this condition is limited as the diagnosis is based on screening of the preterm neonate for this specific condition.
The prognosis and mortality are directly related to the extent of injury with the rate of mortality for grades I through IV at 4%, 10%, 18%, and 40% respectively. Any degree of intraventricular hemorrhage theoretically predisposes to later neurocognitive developments with rates of cerebral palsy for grades I through IV at 8%, 11%, 19%, and 50%. One large multicenter study demonstrated that of 1472 infants less than 27 weeks grade I and II intraventricular hemorrhages were not associated with delay at 2 years of age.
One of the primary complications following intraventricular hemorrhage is post-hemorrhagic hydrocephalus; this can be a communicating or non-communicating form that occurs as a result of impaired CSF reabsorption or by obstruction of the foramen of Monroe. Posthemorrhagic hydrocephalus should be suspected in any preterm infant with IVH that presents with rapidly increasing head circumference. There are multiple proposed treatment strategies for hydrocephalus with elevated intracranial pressure including subgaleal shunt placement, ventricular reservoir placement or ventriculoperitoneal shunt placement.
Intraventricular hemorrhage may also lead to periventricular leukomalacia which is multiple cystic foci in the periventricular space shown to be coagulation necrosis. There have been proposals that periventricular leukomalacia may be the primary cause of neurodevelopmental delay following intraventricular hemorrhage.
Patient education should target risk factor avoidance during pregnancy that would predispose to preterm delivery, including smoking cessation and routine prenatal care.
The care of the preterm infant requires highly specialized facilities that employ an interprofessional teams (i.e., pediatrician, neonatologist, intensivist, radiologist, neurosurgeon, obstetrician, and NICU nurses). When caring for the infant, there has been a demonstrated benefit that reduces the risk of intraventricular hemorrhage in the preterm infant when delivered in a facility that specializes in the care of very low birth weight children (13.2% vs. 27.4%).
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