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Neonatal brain injury influences structural connectivity and childhood functional outcomes
Alice Ramirez1, Shabnam Peyvandi1, Stephany Cox1
1Department of Pediatrics, University of California, San Francisco, San Francisco, California, United States of America.
Insights
Neonatal brain injury from hypoxic-ischemic encephalopathy (HIE) or congenital heart disease (CHD) impacts brain development. Structural brain connectivity predicts motor outcomes, and specific pathways correlate with language development in affected newborns.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Medical Imaging
Background:
- Neonatal brain injury, including hypoxic-ischemic encephalopathy (HIE) and congenital heart disease (CHD), can cause lifelong functional impairments.
- Understanding the distinct impacts of HIE and CHD on brain development is crucial for optimizing outcomes.
Purpose of the Study:
- To compare the effects of HIE and CHD on the development of brain network topology and functional outcomes in newborns.
- To identify neural correlates of neurodevelopmental outcomes, particularly motor and language development, in infants with HIE and CHD.
Main Methods:
- Diffusion magnetic resonance imaging (dMRI) and graph theory metrics were used to quantify whole-brain neural network maturation.
- dMRI data from 35 infants with CHD and 62 infants with HIE were analyzed and compared.
- Statistical analyses controlled for clinical factors affecting neurodevelopmental outcomes.
Main Results:
- Infants with CHD exhibited poorer 12-18 month language and 30-month cognitive, language, and motor outcomes compared to those with HIE.
- Lower global efficiency (brain integration) was observed in the CHD group, associated with motor outcomes.
- Superior longitudinal fasciculus (SLF) connectivity was inversely linked to expressive language, and 18 hypoconnected pathways were identified in the CHD cohort versus HIE.
Conclusions:
- Neonatal structural brain connectivity is a predictor of early motor development in infants with HIE or CHD.
- Regional SLF connectivity is associated with language outcomes, highlighting its importance.
- Further research into dynamic brain network changes is needed to inform strategies for optimizing neurologic function after neonatal brain injury.
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.
