INTRAVENTRICULAR HEMORRHAGE

Essentials of Diagnosis & Typical Features

• Large bleeds are accompanied by hypotension, metabolic acidosis, and altered neurologic status. Smaller bleeds can be asymptomatic.
• Routine cranial ultrasound scanning is essential for diagnosis in infants born at less than 32 weeks’ gestation.

General Considerations
Periventricular-intraventricular hemorrhage occurs almost exclusively in premature infants. The incidence is 20–30% in infants born at less than 31 weeks’ gestation and weighing less than 1500 g at birth. The highest incidence is observed in babies of the lowest gestational age (< 26 weeks). Bleeding most commonly occurs in the subependymal germinal matrix (a region of undifferentiated cells). Bleeding can extend into the ventricular cavity. The proposed pathogenesis of bleeding is presented in Figure 1–7. The critical event is probably ischemia with reperfusion injury to the capillaries in the germinal matrix that occurs in the immediate perinatal period. The actual amount of bleeding is also influenced by a variety of factors that affect the pressure gradient across the injured capillary wall. This pathogenetic scheme applies also to intraparenchymal bleeding (venous infarction in a region rendered ischemic) and to periventricular leukomalacia (ischemic white matter injury in a watershed region of arterial supply). Periventricular leukomalacia has a peak incidence in babies born between 28 and 32 weeks’ gestation and appears to be associated with maternal chorioamnionitis.

Clinical Findings
Up to 50% of hemorrhages occur at less than 24 hours of age, and virtually all occur by the fourth day. The clinical syndrome ranges from rapid deterioration (coma, hypoventilation, decerebrate posturing, fixed pupils, bulging anterior fontanelle, hypotension, acidosis, acute drop in hematocrit) to a more gradual deterioration with more subtle neurologic changes to absence of any specific physiologic or neurologic signs.
The diagnosis can be confirmed by real-time ultrasound scan. This can be performed whenever bleeding is clinically suspected. If symptoms are absent, routine scanning should be done at 10–14 days in all infants born at less than 29 weeks’ gestation. Hemorrhages are graded as follows: grade I, germinal matrix hemorrhage only; grade II, intraventricular bleeding without ventricular enlargement; grade III, intraventricular bleeding with ventricular enlargement; and grade IV, any infant with intraparenchymal bleeding. The amount of bleeding is minor (grade I or II) in 75% of infants and major in the remainder.
Follow-up ultrasound examinations are based on the results of the initial scan. Infants with no bleeding or germinal matrix hemorrhage require only a single late scan at age 4–6 weeks to look for periventricular leukomalacia. Any infant with blood in the ventricular system is at risk for posthemorrhagic ventriculomegaly. This is usually the result of impaired absorption of cerebrospinal fluid (CSF), but it can also occur secondary to obstructive phenomena. An initial follow-up scan should be done 1–2 weeks after the initial scan. Infants with intraventricular bleeding and ventricular enlargement should be followed every 7–10 days until ventricular enlargement stabilizes or decreases. Infants without ventriculomegaly should have one additional scan at age 4–6 weeks. In addition, all infants born at 29–32 weeks’ gestation should have at least a late scan (4–6 weeks) to look for ventriculomegaly and periventricular leukomalacia.

Treatment
During acute hemorrhage, supportive treatment (including restoration of volume and hematocrit, oxygenation, and ventilation) should be provided to avoid further cerebral ischemia. Progressive posthemorrhagic hydrocephalus (if it develops) can sometimes be controlled by decreasing the production of CSF (furosemide, 1 mg/kg/d, plus acetazolamide in increasing doses from 25 to 100 mg/kg/d) or by removal of CSF (daily lumbar punctures). The process is usually self-limited and resolves spontaneously; placement of a ventriculoperitoneal shunt is usually not needed. Early treatment with medications or serial spinal taps does not appear to influence whether a shunt will ultimately be needed but may contribute to an improved long-term neurologic outcome.
Although the incidence and severity of intracranial bleeding have decreased in premature infants, strategies to prevent this complication are still needed. Use of antenatal corticosteroids appears to be important in decreasing this complication, and phenobarbital may have a role in the mother who has not been prepared with steroids and is delivering at less than 28 weeks’ gestation. The route of delivery may also play a role, with babies delivered by cesarean section showing a decreased rate of intracranial bleeds, but this issue remains controversial. Postnatal strategies appear less promising, but early indomethacin may have some benefit.

Prognosis
There are no deaths as a result of grade I and grade II hemorrhages, whereas grade III and grade IV hemorrhages carry a mortality rate of 10–20%. Posthemorrhagic ventricular enlargement is rarely seen with grade I hemorrhages but is seen in 54–87% of grade II–IV hemorrhages. Very few of these infants will require a ventriculoperitoneal shunt. Long-term neurologic sequelae are seen no more frequently in infants with grade I and grade II hemorrhages than in preterm infants without bleeding. In infants with grade III and grade IV hemorrhages, severe sequelae occur in 20–25% of cases, mild sequelae in 35% of cases, and no sequelae in 40% of cases. The presence of severe periventricular leukomalacia, large parenchymal bleeds, and progressive ventriculomegaly greatly increases the risk of neurologic sequelae.