Preterm Infant Outcomes Following Intracranial Hemorrhage
Abstract and Introduction
Objective: Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH.
Study design: Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI).
Result: Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI.
Conclusion: Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.
Neonatologists rely on several prognostic paradigms when counseling families of extremely preterm (EPT) infants about the possibility of adverse outcome. Existing methods utilize antenatal variables, illness severity scoring systems, and early clinical variables. The diagnosis of severe intracranial hemorrhage (ICH) on cranial ultrasound (cUS) is often considered a key variable to predict adverse outcome. Severe ICH, typically defined as grade III or IV by Papile criteria, has been shown to be associated with adverse neurologic outcomes, including moderate- to severe-cerebral palsy (CP), neurodevelopmental impairment (NDI) and even cognitive delay.
The presence of severe neuroimaging findings, though, is not always predictive of adverse early childhood outcome. A single-center study demonstrated that ~50% of extremely low birth weight infants with grade III and IV ICH did not have significant cognitive impairment or neurologic abnormality at 20-month follow-up. Similarly, in a large cohort of extremely low birth weight survivors, 45% of infants with grade III ICH and 30% of infants with grade IV ICH did not have NDI. A more recent report found that, except when accompanied by white matter damage, ICH is not associated with developmental delay. One possible explanation for the range in outcomes reported is that many studies use 'severe ICH' as a composite predictor that does not distinguish between unilateral and bilateral ICH, and hemorrhagic parenchymal infarction (HPI), typically defined as grade IV ICH, is not differentiated from a grade III ICH, or bleeding that is confined to the ventricles.
We hypothesized that specific characteristics of ICH, including bilateral compared with unilateral severe ICH or the presence of HPI, would be important predictors of outcomes of EPT infants with severe ICH. Using data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN), we compared the outcomes of EPT infants with severe ICH, using bilaterality of ICH and presence of HPI as distinct predictor variables. We further hypothesized that this information, in combination with other clinical factors, could be used in multivariable regression analysis and Classification and Regression Tree (CART) modeling to refine the prediction of outcome in this high-risk group.