Retrospective analysis of neurological findings in esophageal atresia: Allostatic load of disease complexity, cumulative sedation, and anesthesia exposure.

BACKGROUND: There is limited knowledge regarding the impact of perioperative critical care on frequency of neurological imaging findings following esophageal atresia (EA) repair. METHODS: This is a retrospective study of infants (n = 70) following EA repair at a single institution (2009-2020). Sex, gestational age at birth, type of surgical repair, underlying disease severity, and frequency of neurologic imaging findings were obtained. We quantified the length of postoperative pain/sedation treatment and anesthesia exposure in the first year of life. Data were presented as numerical sums and percentages, while associations were measured using Spearman's Rho. RESULTS: Vertebral/spinal cord imaging was performed in all infants revealing abnormalities in 44% (31/70). Cranial/brain imaging findings were identified in 67% (22/33) of infants in the context of clinically indicated imaging (47%; 33/70). Long-gap EA patients (n = 16) received 10 times longer postoperative pain/sedation treatment and twice the anesthesia exposure compared with short-gap EA patients (n = 54). The frequency of neurologic imaging findings did not correlate with underlying disease severity scores, length of pain/sedation treatment, or cumulative anesthesia exposure. Lack of associations between clinical measures and imaging findings should be interpreted with caution given possible underestimation of cranial/brain findings. CONCLUSIONS: We propose that all infants with EA undergo brain imaging in addition to routine spinal imaging given the high burden of abnormal brain/cranial findings in our cohort. Quantification of pain/sedation and anesthesia exposure in long-gap EA patients could be used as indirect markers in future studies assessing the risk of neurological sequelae as evidenced by early abnormalities on brain imaging.

Infant Perioperative Risk Factors and Adverse Brain Findings Following Long-Gap Esophageal Atresia Repair.

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.

Impact of Infant Thoracic Non-cardiac Perioperative Critical Care on Homotopic-Like Corpus Callosum and Forebrain Sub-regional Volumes.

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) <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.