Relationship Between MRI Scoring Systems and Neurodevelopmental Outcome at Two Years in Infants With Neonatal Encephalopathy.

BACKGROUND: Magnetic resonance imaging (MRI) scoring systems are used in the neonatal period to predict outcome in infants with neonatal encephalopathy. Our aim was to assess the relationship between three MRI scores and neurodevelopmental outcome assessed using Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), at two years in infants with neonatal encephalopathy. METHODS: Term-born neonates with evidence of perinatal asphyxia born between 2011 and 2015 were retrospectively reviewed. MRI scanning was performed within the first two weeks of life and scored using Barkovich, National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), and Weeke systems by a single assessor blinded to the infants clinical course. Neurodevelopmental outcome was assessed using composite scores on the Bayley-III at two years. Multiple linear regression analyses were used to assess the association between MRI scores and Bayley-III composite scores, with postmenstrual age at scan and sex included as covariates. RESULTS: Of the 135 recruited infants, 90 infants underwent MRI, and of these, 66 returned for follow-up. MRI abnormalities were detected with the highest frequency using the Weeke score (Barkovich 40%, NICHD NRN 50%, Weeke 77%). The inter-rater agreement was good for the Barkovich score and excellent for NICHD NRN and Weeke scores. There was a significant association between Barkovich, NICHD NRN, and Weeke scores and Bayley-III cognitive and motor scores. Only the Weeke score was associated with Bayley-III language scores. CONCLUSIONS: Our findings confirm the predictive value of existing MRI scoring systems for cognitive and motor outcome and suggest that more detailed scoring systems have predictive value for language outcome.

Relationship between resting-state fMRI functional connectivity with motor and language outcome after perinatal brain injury - A systematic review.

Perinatal brain injury is a significant cause of adverse neurodevelopmental outcomes. The objective of this systematic review was to identify patterns of altered brain function, quantified using functional connectivity (FC) changes in resting-state fMRI (rs-fMRI) data, that were associated with motor and language outcomes in individuals with a history of perinatal brain injury. A systematic search using electronic databases was conducted to identify relevant studies. A total of 10 studies were included in the systematic review, representing 260 individuals with a history of perinatal brain injury. Motor and language outcomes were measured at time points ranging from 4 months to 29 years 1 month. Relations between FC and motor measures revealed increased intra-hemispheric FC, reduced inter-hemispheric FC and impaired lateralization of motor-related brain regions associated with motor outcomes. Altered FC within sensorimotor, visual, cerebellum and frontoparietal networks, and between sensorimotor, visual, auditory and higher-order networks, including cerebellum, frontoparietal, default-mode, salience, self-referential and attentional networks were also associated with motor outcomes. In studies assessing the relationship between rs-fMRI and language outcome, reduced intra-hemispheric FC, increased inter-hemispheric FC and right-hemisphere lateralization of language-related brain regions correlated with language outcomes. Evidence from this systematic review suggests a possible association between diaschisis and motor and language impairments in individuals after perinatal brain lesions. These findings support the need to explore the contributions of additional brain regions functionally connected but remote from the primary lesioned brain area for targeted treatments and appropriate intervention, though more studies with increased standardization across neuroimaging and neurodevelopmental assessments are needed.

Dysregulated Monocyte and Neutrophil Functional Phenotype in Infants With Neonatal Encephalopathy Requiring Therapeutic Hypothermia.

Neonatal encephalopathy (NE) is a significant cause of morbidity and mortality. Persistent inflammation and activation of leukocytes mediate brain injury in NE. The standard of care for NE, therapeutic hypothermia (TH), does not improve outcomes in nearly half of moderate to severe cases, resulting in the need for new adjuvant therapies, and immunomodulation holds promise. Our objective was to explore systemic leukocyte phenotype in infants with NE and healthy controls in response to lipopolysaccharide (LPS). Twenty-four infants with NE (NE II-20; NE III = 4) requiring TH and 17 term neonatal controls were enrolled, and blood samples were analyzed between days 1 and 4 of life at a mean (SD) timepoint of 2.1 (± 0.81) days of postnatal life at the time of the routine phlebotomy. Leukocyte cell surface expression levels of Toll-like receptor 4, NADPH oxidase (NOX2), CD11b, mitochondrial mass, and mitochondrial superoxide production were measured by flow cytometry. Gene expression of TRIF (TIR domain-containing adapter-inducing interferon-ß), MyD88 and IRAK4 was measured by reverse transcription-polymerase chain reaction. Infants with NE had significantly lower expression of neutrophil CD11b and NOX2 with LPS stimulation compared to healthy term controls. Mitochondrial mass in neutrophils and monocytes was significantly increased in NE infants with LPS compared to controls, potentially indicating a dysregulated metabolism. Infants with NE had significantly lower IRAK4 at baseline than controls. NE infants display a dysregulated inflammatory response compared to healthy infants, with LPS hyporesponsiveness to CD11b and NOX2 and decreased IRAK4 gene expression. This dysregulated immune profile may indicate an adaptable response to limit hyperinflammation.

Reduced structural connectivity in cortico-striatal-thalamic network in neonates with congenital heart disease.

Impaired brain development has been observed in newborns with congenital heart disease (CHD). We performed graph theoretical analyses and network-based statistics (NBS) to assess global brain network topology and identify subnetworks of altered connectivity in infants with CHD prior to cardiac surgery. Fifty-eight infants with critical/serious CHD prior to surgery and 116 matched healthy controls as part of the developing Human Connectome Project (dHCP) underwent MRI on a 3T system and high angular resolution diffusion MRI (HARDI) was obtained. Multi-tissue constrained spherical deconvolution, anatomically constrained probabilistic tractography (ACT) and spherical-deconvolution informed filtering of tractograms (SIFT2) was used to construct weighted structural networks. Network topology was assessed and NBS was used to identify structural connectivity differences between CHD and control groups. Structural networks were partitioned into core and peripheral nodes, and edges classed as core, peripheral, or feeder. NBS identified one subnetwork with reduced structural connectivity in CHD infants involving basal ganglia, amygdala, hippocampus, cerebellum, vermis, and temporal and parieto-occipital lobe, primarily affecting core nodes and edges. However, we did not find significantly different global network characteristics in CHD neonates. This locally affected sub-network with reduced connectivity could explain, at least in part, the neurodevelopmental impairments associated with CHD.