Thiviya Selvanathan

Fetal cerebral sinovenous thrombosis (CSVT) is a rare cerebrovascular disorder. We report the neuroimaging evolution and clinical trajectory of 2 children with CSVT detected on fetal MRI. Serial im...

Background: White matter injury (WMI) is a prevalent form of brain injury in preterm infants. Although magnetic resonance imaging (MRI) can identify WMI early in life, mechanisms underlying WMI heterogeneity remain unclear. DNA methylation (DNAme), an epigenetic mark responsive to developmental and environmental exposures, may capture molecular variation relevant to WMI. Methods: We investigated 95 preterm infants with buccal DNA collected at the neonatal period and at term-equivalent age (TEA), profiled for genome-wide DNAme, alongside MRI-based WMI volume (mm3) and neurodevelopmental assessments at 18 months. An internal validation subset of 46 preterm infants with additional data at 36 months was used to examine the trajectory of WMI-associated DNAme into early childhood. Findings: WMI-associated DNAme signatures were identified at both single CpG and co-methylated regions during the neonatal period. Effect sizes were concordant at TEA in the 95 infants and in the validation subset but progressively attenuated by 36 months. Four WMI-associated CpGs were linked to postnatal infections. While higher WMI volume was associated with poorer motor outcomes at 18 months, no significant mediation through WMI-associated DNAme loci was observed. Interpretation: Molecular signatures of WMI are detectable in the neonatal methylome and persist to TEA. Overlap between WMI- and infection-associated DNAme signals may reflect a shared epigenetic record of the broader neonatal inflammatory milieu. These findings highlight the buccal epigenome as an informative, non-invasive window into WMI, contributing to the nascent field of neuroimaging epigenetics. Funding: Supported primarily by the Canadian Institutes of Health Research and the Kids Brain Health Network.

Background and ObjectivesChildren with congenital heart disease (CHD) are at greater risk of neurodevelopmental (ND) delays and disorders than those with normal hearts. However, the cardiovascular ...

Infants with critical congenital heart disease (CHD) are at increased risk of brain injury and neurodevelopmental impairments, with variable rates of ischemic brain injury reported across studies. In this systematic review and meta-analysis, we aimed to understand the overall prevalence of ischemic brain injury and associated risk factors in infants with critical CHD. A systematic review and meta-analysis was performed using a prespecified protocol registered on PROSPERO (CRD42021268352). Primary, original research in English reporting the prevalence of ischemic brain injury in neonates with critical CHD was included. Case reports and series were excluded. The search was conducted based on all article titles and abstracts published in MEDLINE, Embase, and Cochrane from inception to 2024. The Newcastle-Ottawa Scale for Cohort Studies and the revised Cochrane risk-of-bias tool for randomized trials were used to assess risk of bias. Random-effects restricted maximum likelihood models were used to calculate pooled prevalence rates. Funnel plots and Egger tests were used to assess publication bias. We explored associations with year of study, age at surgery, and female sex proportion using meta-regression analyses. We identified 31 studies that reported the prevalence of ischemic brain injury in neonates with CHD. The pooled cumulative prevalence of ischemic brain injury among neonates with CHD was 68.5% (95% CI 62.7%-73.8%), with low between-study heterogeneity (I² = 3.0%, Qp value = 0.4). The pooled cumulative prevalence of preoperative ischemic brain injury was 34.7% (95% CI 28.4%-41.5%), with moderate between-study heterogeneity (I² = 43.4%, Qp value = 0.05), and that of new postoperative ischemic brain injury was 46.5% (95% CI 34.8%-58.5%), with substantial between-study heterogeneity (I² = 69.1%, Qp value = 0.004). Age at surgery and female sex proportion were associated with cumulative white matter injury and preoperative arterial ischemic stroke, respectively. The prevalence of ischemic brain injury in neonates with CHD is high and depends on brain injury type and timing. Identifying ischemic injuries in this population is important for counseling families about expected neurodevelopmental outcomes and beginning early neurodevelopmental surveillance and interventions. Significant heterogeneity exists in the literature; to improve outcomes, further research is warranted to determine modifiable risk factors and neuroprotective strategies.

We determined whether white matter injury (WMI) severity and location on early-life vs term-equivalent age (TEA) brain MRI were more strongly associated with 36-month neurodevelopment. Very preterm infants were recruited across 3 tertiary NICUs and underwent early-life and TEA MRI. Moderate-severe WMI severity and anterior or posterior location were scored. 36-month neurodevelopmental assessments were completed with Bayley Scales of Infant Development, Third Edition; delay was defined as a composite score <85 points. Multivariable logistic regressions adjusting for birth gestational age, site, infection, retinopathy of prematurity, moderate-severe intraventricular hemorrhage, and antenatal magnesium sulfate were used to determine associations of WMI severity and location at each scan with neurodevelopment. A total of 393 neonates (postmenstrual age median 27.6, SD 2.3 weeks, 47% female) completed early-life and TEA MRI scans. Cognitive delay was associated with early-life moderate-severe (OR 3.82, 95% CI 1.17-9.14) and anterior (OR 5.47, 95% CI 1.72-17.29) WMI. Motor delay was associated with early-life anterior WMI (OR 3.02, 95% CI 1.12-8.2). These associations were not observed at TEA in multivariable logistic regressions. Moderate-severe and anterior WMI on early-life, but not TEA, MRI were associated with neurodevelopmental outcomes. Early-life MRI may represent a more optimal time point for assessing WMI in very preterm infants.