Objectives Previous studies have demonstrated that infants are typically born with a left‐greater‐than‐right forebrain asymmetry that reverses throughout the first year of life. We hypothesized that critically ill term‐born and premature patients following surgical and critical care for long‐gap esophageal atresia (LGEA) would exhibit alteration in expected forebrain asymmetry. Methods Term‐born (n = 13) and premature (n = 13) patients, and term‐born controls (n = 23) <1 year corrected age underwent non‐sedated research MRI following completion of LGEA treatment via Foker process. Structural T1‐ and T2‐weighted images were collected, and ITK‐SNAP was used for forebrain tissue segmentation and volume acquisition. Data were presented as absolute (cm3) and normalized (% total forebrain) volumes of the hemispheres. All measures were checked for normality, and group status was assessed using a general linear model with age at scan as a covariate. Results Absolute volumes of both forebrain hemispheres were smaller in term‐born and premature patients in comparison to controls (p < 0.001). Normalized hemispheric volume group differences were detected by T1‐weighted analysis, with premature patients demonstrating right‐greater‐than‐left hemisphere volumes in comparison to term‐born patients and controls (p < 0.01). While normalized group differences were very subtle (a right hemispheric predominance of roughly 2% of forebrain volume), they represent a deviation from the expected pattern of hemispheric brain asymmetry. Interpretation Our pilot quantitative MRI study of hemispheric volumes suggests that premature patients might be at risk of altered expected left‐greater‐than‐right forebrain asymmetry following repair of LGEA. Future neurobehavioral studies in infants born with LGEA are needed to elucidate the functional significance of presented anatomical findings.

Previously, we reported quantitatively smaller total corpus callosum (CC) and total forebrain size in critically ill term-born and premature patients following complex perioperative critical care for long-gap esophageal atresia (LGEA) that included Foker process repair. We extended our cross-sectional pilot study to determine sub-regional volumes of CC and forebrain using structural brain MRI. Our objective was to evaluate region-specific CC as an in-vivo marker for decreased myelination and/or cortical neural loss of homotopic-like sub-regions of the forebrain. Term-born (n = 13) and premature (n = 13) patients, and healthy naïve controls (n = 21) &lt;1-year corrected age underwent non-sedated MRI using a 3T Siemens scanner, as per IRB approval at Boston Children's Hospital following completion of clinical treatment for Foker process. We used ITK-SNAP (v.3.6) to manually segment six sub-regions of CC and eight sub-regions of forebrain as per previously reported methodology. Group differences were assessed using a general linear model univariate analysis with corrected age at scan as a covariate. Our analysis implicates globally smaller CC and forebrain with sub-region II (viz. rostral body of CC known to connect to pre-motor cortex) to be least affected in comparison to other CC sub-regions in LGEA patients. Our report of smaller subgenual forebrain implicates (mal)adaptation in limbic circuits development in selected group of infant patients following LGEA repair. Future studies should include diffusion tractography studies of CC in further evaluation of what appears to represent global decrease in homotopic-like CC/forebrain size following complex perioperative critical care of infants born with LGEA.

Recent findings implicate brain vulnerability following long-gap esophageal atresia (LGEA) repair. We explored the relationship between easily quantifiable clinical measures and previously reported brain findings in a pilot cohort of infants following LGEA repair. MRI measures (number of qualitative brain findings; normalized brain and corpus callosum volumes) were previously reported in term-born and early-to-late premature infants (n = 13/group) <1 year following LGEA repair with the Foker process. The severity of underlying disease was classified by an (1) American Society of Anesthesiologist (ASA) physical status and (2) Pediatric Risk Assessment (PRAm) scores. Additional clinical end-point measures included: anesthesia exposure (number of events; cumulative minimal alveolar concentration (MAC) exposure in hours), length (in days) of postoperative intubated sedation, paralysis, antibiotic, steroid, and total parenteral nutrition (TPN) treatment. Associations between clinical end-point measures and brain MRI data were tested using Spearman rho and multivariable linear regression. Premature infants were more critically ill per ASA scores, which showed a positive association with the number of cranial MRI findings. Clinical end-point measures together significantly predicted the number of cranial MRI findings for both term-born and premature infant groups, but none of the individual clinical measures did on their own. Listed easily quantifiable clinical end-point measures could be used together as indirect markers in assessing the risk of brain abnormalities following LGEA repair.