Perioperative Zinc Supplementation and Pediatric Colonic Surgical Recovery

This study is a single-center, single-blinded, parallel-group randomized controlled clinical trial conducted at Nile of Hope Hospital for Pediatric Congenital Anomalies Surgery in Alexandria, Egypt.

• Pathophysiology & Rationale: Pediatric colonic surgical procedures-indicated for conditions such as Hirschsprung disease, anorectal malformations, colonic atresia, colonic resections, or colostomy closures-trigger a complex, multi-phase intestinal mucosal healing response involving initial inflammation, cell proliferation, and tissue remodeling. Impaired healing increases the risk of severe complications such as anastomotic leaks and surgical site infections, necessitating prolonged parenteral nutrition and intensive supportive care. Zinc is a critical trace element in maintaining gastrointestinal mucosal barrier integrity. It stabilizes epithelial cell tight junctions, diminishes intestinal permeability, and protects against oxidative tissue damage via antioxidant enzyme activation (e.g., superoxide dismutase and metallothioneins). Following surgical trauma, circulating serum zinc levels typically decline due to systemic inflammatory redistribution, accelerated urinary excretion, and temporary cessation of oral intake. Concurrently, acute-phase inflammatory markers such as C-reactive protein (CRP)-regulated primarily by interleukin-6 (IL-6)-and complete blood count (CBC) inflammatory indices (e.g., white blood cell count and neutrophil-to-lymphocyte ratio) rise.

Perioperative zinc supplementation is hypothesized to mitigate this inflammatory surge, downregulate pro-inflammatory cytokine activity (including TNF-alpha and IL-6), accelerate mucosal re-epithelialization, and improve systemic and local surgical recovery.

• Randomization, Allocation & Blinding: Eligible pediatric patients undergoing elective or semi-urgent colonic surgery with anastomosis are enrolled via consecutive screening. Participants are allocated in a 1:1 ratio using a computer-generated permuted block randomization sequence, stratified by age group and specific type of colonic surgery.
• This trial utilizes a single-blind design:

Unblinded personnel: Caregivers, ward nurses, and treating clinicians manage drug administration and direct patient care.

Blinded personnel: Outcome assessors, clinical adjudicators, laboratory staff analyzing blood specimens, and the biostatistician performing the primary statistical analyses will remain fully blinded to treatment assignments. Study Procedures & Data Collection.

• Intervention: Group A receives standard-of-care postoperative surgical management supplemented with perioperative oral zinc. Group B receives standard-of-care postoperative management alone. Supplementation details and administration adherence are documented using standardized nursing medication charts and outpatient logbooks.
• Laboratory Assessments: Venous blood samples are drawn across three discrete time points: baseline (preoperative), 48 hours postoperatively, and Day 5 postoperatively. Specimens are handled using standardized operating procedures (SOPs) for blood collection, refrigeration, and processing. Parameters analyzed include CBC and CRP (analyzed using consistent internal hospital analyzers) alongside quantitative serum zinc concentrations.
• Clinical Monitoring & Outcome Assessment: Patients undergo daily in-hospital ward evaluations through postoperative Day 7. Secondary clinical endpoints-such as fever, time to passage of flatus/stool, presence of audible peristalsis, and orogastric suction output-and potential surgical complications are documented on standardized Case Report Forms (CRFs) and adjudicated by a blinded clinical committee. Wound healing at the surgical site is graded on Day 7 using a validated 0-3 point scale (0 = normal, 1 = mild erythema, 2 = partial dehiscence, 3 = full dehiscence/necrosis).
• Sample Size Calculation: The sample size determination was based on detecting differences in primary continuous inflammatory markers (specifically CRP) between independent groups. Assuming a standardized mean difference of 1.082 with a common standard deviation of 1.1 based on previous pediatric zinc trial literature, a significance level (α) of 0.01, and 90% statistical power (β), a minimum of 28 evaluable subjects per group is required. Accounting for an anticipated 15% drop-out or loss to follow-up, total enrollment is set at 66 participants (33 in Group A, 33 in Group B).

Inclusion criteria

• Age: 1 month to 18 years.
• Undergoing elective or semi urgent colonic surgery with anastomosis (e.g., Hirschsprung's disease, anorectal malformations, colonic atresia, colonic resection, closure of colostomy).
• Parent/guardian able to give informed consent and agree to follow-up.

Exclusion criteria

• Preoperative serum zinc deficiency
• Development of major postoperative surgical complications that would interfere with the intervention or outcome assessment.
• Known severe renal impairment (eGFR below local pediatric threshold).
• Known severe hepatic failure.
• Current participation in another interventional trial that would interfere with outcomes.
• Immunodeficiency (primary or secondary) or neutropenia (because of atypical healing responses).
• Neonates <1 month old (due to safety and dosing differences).