## 2 Materials and Methods  
### Study Design and Subjects  
As an extension of our previous work [16; 17; 18], this pilot study was approved by the Boston Children's Hospital Review Board as a 'no more than minimal risk' study. Informed written consent was obtained from parents before participation in accordance with the Declaration of Helsinki and Good Clinical Practice. Patients were eligible to participate if they were less than 12 months old and were selected to undergo the Foker process [19; 20; 21] for treatment of LGEA. Exclusion criteria included: (1) any known neurological disease (e.g., seizures); (2) cranial ultrasound findings (e.g., ventricular enlargement, hemorrhage); (3) chromosomal abnormalities (e.g., Down's Syndrome); (4) prenatal drug exposure; (5) extreme prematurity (<28 weeks GA); and/or (6) MRI incompatible implants. Subjects were categorized into moderate-to-late preterm [born 28- to 36 weeks gestational age (GA)] and full-term (born 37- to 42 weeks GA) infants. Complex perioperative care included several stages [23]: (1) Foker I thoracotomy to place traction sutures onto blind esophageal ends; (2) Esophageal lengthening, which uses continuous traction on the esophagus to induce esophageal growth; (3) Foker II thoracotomy to approximate esophageal ends and perform primary esophageal anastomosis; (4) Post-Foker healing of the anastomosis. To facilitate postoperative mechanical ventilation, infants underwent prolonged sedation (\(\geq\)5 days), that led to pharmacological dependence to sedative agents [12; 24; 25] requiring subsequent weaning from sedation medications (viz. opioids and benzodiazepines). Although we did not analyze potential symptoms of withdrawal or withdrawal prevention management (for Review on weaning treatment, see [26]), we confirmed that extended administration of opioids and benzodiazepines was indicated specifically for weaning management as per primary team and/or pain service consult notes. In this pilot case report, subjects were categorized and named as Preterm 1, 2, 3 and Term 1, 2, 3 in order of increasing corrected age at time of post-Foker MRI scan. Baseline demographics and clinical information for each patient are displayed in Tables 1 and 2. \begin{table}
\begin{tabular}{l c c c c c c} \hline \hline
**Baseline Demographics** & **Preterm 1** & **Preterm 2** & **Preterm 3** & **Term 1** & **Term 2** & **Term 3** \\ \hline Sex & F & M & F & F & M & M \\ \hline Race & White & White & AA & AA & Hispanic & Other \\ \hline Gestational age (weeks) & 33 & 34 & 28 & 37 & 39 & 37 \\ \hline Birth weight (kg) & 2.64 & 1.87 & 0.55 & 2.8 & 3.03 & Unknown \\ \hline Birth by cesarean section & No & No & Yes & Yes & Yes & Unknown \\ \hline
**Clinical Information** & & & & & & \\ \hline Initial Admission Service & NICU & NICU & MSICU & NICU & MSICU & MSICU \\ \hline Main Diagnosis & LGEA & LGEA/TEF & LGEA & LGEA & LGEA/TEF & LGEA/TEF \\ \hline Secondary Diagnoses & - & - & pHTN, IUGR, FIT & - & - & TOF \\ \hline
**Prior to PRE- Foker** & & & & & & \\
**MRI Scan** & & & & & & \\ \hline Total number of & & & & & & \\ Surgical Events & 4 & 2 & 4 & 1 & 4 & 5 \\ \hline MAC Equivalent & & & & & & \\ Anesthesia (h) & 2.25 & 8.00 & 2.50 & 0.62 & 14.12 & 19.18 \\ \hline
**Between PRE- and** & & & & & & \\
**POST-Foker Scans** & & & & & & \\ \hline Total number of & & & & & & \\ Surgical Events & 3 & 8 & 13 & 3 & 8 & 17 \\ \hline MAC Equivalent & & & & & & \\ Anesthesia (h) & 15.90 & 34.30 & 56.38 & 17.53 & 30.55 & 27.80 \\ \hline Length of Muscle & & & & & & \\ Relaxation (days) & 12 & 20 & 39 & 3 & 19 & 6 \\ \hline Length of Intubation/ & & & & & & \\ Sedation (days) & 15 & 57 & 83 & 11 & 48 & 14 \\ \hline Length of Weaning of & & & & & & \\ Sedation (days) & 17 & * & 44 & 13 & 16 & 12 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Baseline Demographics and Clinical Information.