Background Characterization of brain injury and neurodevelopmental (ND) outcomes in critical congenital heart disease (cCHD) has primarily focused on hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). This study reports brain injury and ND outcomes among patients with heterogeneous cCHD diagnoses beyond HLHS and TGA. Methods This prospective cohort study included infants with HLHS, TGA, or heterogenous “Other cCHD” including left- or right-sided obstructive lesions, anomalous pulmonary venous return, and truncus arteriosus. Brain injury on perioperative brain MRI and ND outcomes on the Bayley-II at 30 months were compared. Results A total of 218 participants were included (HLHS = 60; TGA = 118; “Other cCHD” = 40, including 8 with genetic syndromes). Pre-operative (n = 209) and post-operative (n = 189) MRI showed similarly high brain injury rates across groups, regardless of cardiopulmonary bypass exposure. At 30 months, participants with “Other cCHD” had lower cognitive scores (p = 0.035) compared to those with HLHS and TGA, though worse ND outcome in this group was driven by those with genetic disorders. Conclusions Frequency of brain injury and neurodevelopmental delay among patients with “Other cCHD” is similar to those with HLHS or TGA. Patients with all cCHD lesions are at risk for impaired outcomes; developmental and genetic screening is indicated. Impact This study adds to literature on risk of brain injury in patients with critical congenital heart disease (cCHD) diagnoses other than hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), a heterogenous cohort of patients that has often been excluded from imaging studies. Children with cCHD beyond HLHS and TGA have similarly high rates of acquired brain injury. The high rate of neurodevelopmental impairment in this heterogenous group of cCHD diagnoses beyond HLHS and TGA is primarily driven by patients with comorbid genetic syndromes such as 22q11.2 deletion syndrome.

OBJECTIVES: Pediatric out-of-hospital cardiac arrest (OHCA) is associated with substantial morbidity and mortality. Limited data exist to guide timing and method of neurologic prognostication after pediatric OHCA, making counseling on withdrawal of life-sustaining therapies (WLSTs) challenging. This study investigates the timing and mode of death after pediatric OHCA and factors associated with mortality. Additionally, this study explores delayed recovery after comatose examination on day 3 postarrest. DESIGN: This is a retrospective, observational study based on data collected from hospital databases and chart reviews. SETTING: Data collection occurred in two pediatric academic hospitals between January 1, 2016, and December 31, 2020. PATIENTS: Patients were identified from available databases and electronic medical record queries for the International Classification of Diseases, 10th Edition (ICD-10) code I46.9 (Cardiac Arrest). Patient inclusion criteria included age range greater than or equal to 48 hours to less than 18 years, OHCA within 24 hours of admission, greater than or equal to 1 min of cardiopulmonary resuscitation, and return-of-spontaneous circulation for greater than or equal to 20 min. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-five children (65% male) with a median age of 3 years (interquartile range 0.6–11.8) met inclusion criteria. Overall, 63 of 135 patients (47%) died before hospital discharge, including 34 of 63 patients (54%) after WLST. Among these, 20 of 34 patients underwent WLST less than or equal to 3 days postarrest, including 10 of 34 patients who underwent WLST within 1 day. WLST occurred because of poor perceived neurologic prognosis in all cases, although 7 of 34 also had poor perceived systemic prognosis. Delayed neurologic recovery from coma on day 3 postarrest was observed in 7 of 72 children (10%) who ultimately survived to discharge. CONCLUSIONS: In our two centers between 2016 and 2020, more than half the deaths after pediatric OHCA occurred after WLST, and a majority of WLST occurred within 3 days postarrest. Additional research is warranted to determine optimal timing and predictors of neurologic prognosis after pediatric OHCA to better inform families during goals of care discussions.

Objective: This study examines associations among fetal brain magnetic resonance imaging (MRI) injury patterns, etiologies, and outcomes in fetal intraparenchymal hemorrhage (IPH).Methods: This is a retrospective, single‐center cohort study of IPH diagnosed on fetal MRI (1996–2022). IPH and associated abnormalities were categorized by 2 pediatric neuroradiologists; electronic medical records were reviewed by 2 pediatric neurologists to classify etiology and outcomes including cerebral palsy, epilepsy, developmental delay, and death.Results: Forty‐four fetuses with IPH were identified (34 singleton and 10 twin gestations) with MRI at median 24 weeks gestation (interquartile range [IQR] = 22–28 weeks). IPH was commonly supratentorial (84%) and focal (50%) or focal with diffuse injury (43%) and was often associated with germinal matrix hemorrhage (GMH; 75%) and/or intraventricular hemorrhage (IVH; 52%). An etiology was identified in 75%, including twin‐twin transfusion syndrome (TTTS, n = 10), COL4A1/2 variants (n = 8), or other fetal/maternal conditions (n = 15). COL4A1/2 variants were associated with focal IPH and the presence of hemorrhagic porencephaly, and intrauterine transfusion was associated with infratentorial hemorrhage. Twenty‐two fetuses were liveborn, and 18 pregnancies were terminated. Among those with follow‐up ≥ 12 months (median = 7 years), 12 of 13 had cerebral palsy, 6 of 13 had developmental delay, and 5 of 13 had epilepsy.Interpretation: An etiology for fetal IPH with or without GMH‐IVH is identified in most cases in our cohort and is commonly TTTS, COL4A1/2 variants, or other maternal/fetal comorbidities. Pattern of fetal IPH on MRI is associated with etiology. Cerebral palsy and neurodevelopmental impairment were common in liveborn infants. Genetic studies should be considered in cases of fetal IPH without an otherwise apparent cause. ANN NEUROL 2024;96:1137–1147

Semi-automated diffusion tensor imaging (DTI) analysis of white matter (WM) microstructure offers a clinically feasible technique to assess neonatal brain development and provide early prognosis, but is limited by variable methods and insufficient evidence regarding optimal parameters. The purpose of this research was to investigate the influence of threshold values on semi-automated, atlas-based brain segmentation in very-low-birth-weight (VLBW) preterm infants at near-term age. DTI scans were analyzed from 45 VLBW preterm neonates at near-term-age with no brain abnormalities evident on MRI. Brain regions were selected with a neonatal brain atlas and threshold values: trace 0.15, FA>0.20, and FA>0.25. Relative regional volumes, FA, axial diffusivity (AD), and radial diffusivity (RD) were compared for twelve WM regions. Near-term brain regions demonstrated differential effects from segmentation with the three FA thresholds. Regional DTI values and volumes selected in the PLIC, CereP, and RLC varied the least with the application of different FA thresholds. Overall, application of higher FA thresholds significantly reduced brain region volume selected, increased variability, and resulted in higher FA and lower RD values. The lower threshold FA>0.15 selected 78±21% of original volumes segmented by the atlas, compared to 38±12% using threshold FA>0.25. Results indicate substantial and differential effects of atlas-based DTI threshold parameters on regional volume and diffusion scalars. A lower, more inclusive FA threshold than typically applied for adults is suggested for consistent analysis of WM regions in neonates.