Abstract
Neonatal brain injury may impact brain development and lead to lifelong functional impairments. Hypoxic-ischemic encephalopathy (HIE) and congenital heart disease (CHD) are two common causes of neonatal brain injury differing in timing and mechanism. Maturation of whole-brain neural networks can be quantified during development using diffusion magnetic resonance imaging (dMRI) in combination with graph theory metrics. DMRI of 35 subjects with CHD and 62 subjects with HIE were compared to understand differences in the effects of HIE and CHD on the development of network topological parameters and functional outcomes. CHD newborns had worse 12-18 month language (P<0.01) and 30 month cognitive (P<0.01), language (P = 0.05), motor outcomes (P = 0.01). Global efficiency, a metric of brain integration, was lower in CHD (P = 0.03) than in HIE, but transitivity, modularity and small-worldness were similar. After controlling for clinical factors known to affect neurodevelopmental outcomes, we observed that global efficiency was highly associated with 30 month motor outcomes (P = 0.02) in both groups. To explore neural correlates of adverse language outcomes in CHD, we used hypothesis-based and data-driven approaches to identify pathways with altered structural connectivity. We found that connectivity strength in the superior longitudinal fasciculus (SLF) tract 2 was inversely associated with expressive language. After false discovery rate correction, a whole connectome edge analysis identified 18 pathways that were hypoconnected in the CHD cohort as compared to HIE. In sum, our study shows that neonatal structural connectivity predicts early motor development after HIE or in subjects with CHD, and regional SLF connectivity is associated with language outcomes. Further research is needed to determine if and how brain networks change over time and whether those changes represent recovery or ongoing dysfunction. This knowledge will directly inform strategies to optimize neurologic functional outcomes after neonatal brain injury.
Highlights
We found that connectivity strength in the superior longitudinal fasciculus (SLF) tract 2 was inversely associated with expressive language
Hypoxic-ischemic encephalopathy (HIE) and severe congenital heart disease (CHD) are two of the most common sources of term neonatal brain injury [1], injury timing and mechanism is markedly different between the two conditions
In this study of two well characterized cohorts at risk for neonatal brain injury, we found that CHD newborns had significantly worse language function at 12–18 months, and worse cognitive, language and motor function at 30 months compared with HIE newborns treated with hypothermia therapy
Summary
Hypoxic-ischemic encephalopathy (HIE) and severe congenital heart disease (CHD) are two of the most common sources of term neonatal brain injury [1], injury timing and mechanism is markedly different between the two conditions. Chronic disruption of brain oxygen delivery and brain growth in the third trimester in CHD may disrupt the formation and refinement of brain networks; whereas in HIE, acute or subacute brain injury damages or destroys brain connections that hitherto developed normally. Comparing these two cohorts with markedly different timing and mechanism of neonatal brain injury provides a ‘natural experiment’ to understand the consequences on different brain injuries on brain development
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