**Background:** Long-gap esophageal atresia (LGEA) is a rare congenital anomaly requiring complex surgical repair via the Foker process, which involves tension-induced esophageal growth over weeks, at least two thoracotomies/thoracoscopies, and prolonged postoperative sedation (≥5 days). Recent pilot MRI studies have raised concerns about brain vulnerability in these infants, but the relationship between easily quantifiable clinical measures and brain findings had not been systematically examined. This study aimed to analyze associations between disease severity scores (ASA, PRAm), clinical care measures (anesthesia exposure, sedation duration, antibiotic/steroid/TPN days), and previously reported brain MRI findings.
**Methods:** This cross-sectional pilot study included 26 infants (13 term-born, 13 early-to-late premature) who underwent research brain MRI under natural sleep in the first year of life following LGEA repair with the Foker process (2015-2018). Exclusion criteria included extreme prematurity (<28 weeks GA), SGA/IUGR, cardiac arrest, ECMO exposure, tracheostomy, abnormal cranial ultrasound findings, neurological disease, chromosomal abnormalities, prenatal drug exposure, and MRI-incompatible implants. Brain MRI measures included: (1) number of qualitative cranial findings (novel data), (2) normalized total brain volume (% of intracranial volume), and (3) normalized corpus callosum volume (% of total forebrain volume). Clinical measures collected from medical records included: ASA physical status score, PRAm score, number of anesthesia events, cumulative MAC-equivalent anesthesia hours, and days of postoperative mechanical ventilation, muscle relaxation, antibiotics, steroids, and TPN. Associations were tested using Spearman rho correlation (Bonferroni-corrected p < 0.01) and multivariable linear regression (p < 0.05).
**Key Results:** Premature infants had higher ASA scores (69% ASA IV vs. equal III/IV distribution in term-born). No significant associations were found between individual disease severity scores (ASA, PRAm) and brain MRI measures. Anesthesia exposure showed significant positive associations with age in both groups (premature: # events r(13)=0.827, p<0.001; cumulative MAC hours r(13)=0.878, p<0.001; term-born: # events r(13)=0.817, p=0.001; cumulative MAC hours r(13)=0.709, p=0.007). Only length of antibiotic treatment was significantly associated with number of cranial MRI findings in premature infants (r(12)=0.718, p=0.009). No individual clinical measures showed significant associations with normalized brain volume or corpus callosum volume, though longer steroid treatment was significantly associated with larger normalized corpus callosum volume in premature infants (r(12)=0.760, p=0.004), a paradoxical finding the authors caution may be due to small sample size. The multivariable regression model showed that group status and six clinical measures together significantly predicted the number of cranial MRI findings (F(6,14)=3.12, p=0.037), but no individual variable was independently significant. The model did not significantly predict total brain volume (F(6,14)=1.11, p=0.405) or corpus callosum volume (F(6,14)=0.99, p=0.655).
**Clinical Implications:** Individual clinical parameters are of limited use as standalone predictors of brain findings after LGEA repair, but their combination may serve as an early indirect indicator of neurological risk. The findings highlight the need for larger multicenter studies to validate combined clinical measures as risk markers, and call for both early and long-term neurodevelopmental follow-up in this population. The study is limited by its small convenience sample (n=13/group), non-uniform timing of MRI scans, lack of pre-treatment baseline imaging, potential underestimation of anesthesia exposure from outside hospitals, and non-protocolized sedation management. Prematurity remains a significant confounder, and future studies should include at least 16 subjects per sex/gestational group to detect meaningful differences.