Introduction
Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of ganglion cells in the distal bowel, leading to functional intestinal obstruction. While surgical pull-through remains the definitive treatment, postoperative complications, particularly Hirschsprung-associated enterocolitis (HAEC), continue to pose a significant threat to pediatric patients. HAEC is the leading cause of morbidity and mortality in this population, with an incidence ranging from 17% to 50% post-surgery. Recent clinical observations have highlighted that preoperative undernutrition is prevalent among children with HSCR, potentially compromising the intestinal mucosal barrier and immune response. This multicenter randomized controlled trial (RCT) sought to determine whether targeted preoperative nutritional support could mitigate the risk of early postoperative HAEC.
Highlights
- A prospective multicenter RCT involving 110 patients showed that preoperative nutritional support (PNS) significantly reduces the incidence of postoperative HAEC.
- The incidence of HAEC at 3 months post-surgery was 7.27% in the PNS group compared to 29.09% in the standard medical care (SMC) group.
- PNS achieved an absolute risk reduction of 21.82%, with no reported adverse events, underscoring its safety and efficacy.
The Clinical Burden of Undernutrition in HSCR
Children with HSCR often suffer from chronic malnutrition due to persistent bowel obstruction, impaired nutrient absorption, and the systemic metabolic stress of the disease. Undernutrition is not merely a comorbid state; it is a pathophysiological driver that weakens the intestinal epithelial barrier and alters the gut microbiota. In the context of HSCR, a compromised barrier is more susceptible to bacterial translocation and inflammation, the hallmarks of HAEC. Despite the known risks of malnutrition in surgical outcomes, standardized protocols for preoperative nutritional optimization in HSCR have been largely absent, leaving a significant gap in evidence-based care.
Study Design and Methodology
The trial was a prospective, multicenter, open-label randomized controlled trial conducted across seven tertiary hospitals in China between January 2021 and October 2022. The study enrolled 110 pediatric patients scheduled for pull-through surgery for HSCR. Participants were randomized 1:1 into two groups:
Preoperative Nutritional Support (PNS) Group
Fifty-five patients received a structured nutritional intervention prior to surgery. This intervention was tailored to meet metabolic demands and address specific deficiencies identified during preoperative assessment, aiming to optimize the patient’s physiological state before the surgical stressor.
Standard Medical Care (SMC) Group
Fifty-five patients received standard preoperative care as per existing hospital protocols, which did not include a standardized, intensified nutritional support regimen.
The primary endpoint was the incidence of HAEC within 3 months following the pull-through procedure. The diagnosis of HAEC was based on standardized clinical criteria, including abdominal distension, foul-smelling diarrhea, fever, and radiological findings.
Key Findings and Statistical Analysis
The results of the trial demonstrate a profound benefit for the PNS group. At the 3-month postoperative follow-up, the incidence of HAEC was significantly lower in the PNS group (4/55, 7.27%) than in the SMC group (16/55, 29.09%).
Efficacy Outcomes
The absolute risk reduction (ARR) was calculated at 21.82% (95% CI: -35.64% to -7.99%). The statistical significance was robust, with a p-value of 0.003. These data suggest that for approximately every five children treated with preoperative nutritional support, one case of HAEC is prevented (Number Needed to Treat, NNT ≈ 5).
Safety Profile
Safety was a secondary focus of the study. No adverse events related to the nutritional interventions—such as metabolic disturbances or gastrointestinal intolerance to the supplements—were documented. This suggests that the intervention is not only effective but also well-tolerated in the pediatric HSCR population.
Mechanistic Insights and Biological Plausibility
The reduction in HAEC incidence through nutritional support likely stems from several synergistic mechanisms. Adequate protein and micronutrient intake are essential for maintaining the integrity of tight junctions in the intestinal epithelium. By reinforcing this physical barrier, PNS may prevent the translocation of pathogenic bacteria into the bowel wall. Furthermore, nutritional optimization supports the mucosal immune system, including the production of secretory IgA, which is vital for regulating the gut microbiome and preventing the overgrowth of HAEC-associated pathogens.
Expert Commentary
This multicenter trial provides high-level evidence for a relatively low-cost intervention that can significantly alter the postoperative trajectory of HSCR patients. While pull-through surgery addresses the anatomical defect, it does not immediately restore normal bowel physiology or the patient’s nutritional status. The findings suggest that “prehabilitation”—optimizing the patient before they reach the operating room—is just as crucial as the technical execution of the surgery itself.
However, some limitations must be acknowledged. The open-label nature of the study may introduce bias in symptom reporting, although the objective nature of HAEC diagnostic criteria (fever, radiological signs) helps mitigate this. Additionally, the study was conducted in tertiary hospitals in China; further research is needed to determine if these results are generalizable to different healthcare settings or specialized patient subgroups, such as those with total colonic aganglionosis.
Conclusion
Preoperative nutritional support is a highly effective intervention for reducing the risk of early HAEC in children undergoing surgery for Hirschsprung disease. Given the high morbidity associated with enterocolitis, implementing a standardized nutritional assessment and support protocol should be considered a priority in the preoperative management of these patients. This study marks a significant step toward a more holistic, evidence-based approach to pediatric colorectal surgery.
Funding and Clinical Trial Registration
This study was supported by multicenter research grants and registered at ClinicalTrials.gov (NCT04598841).
References
- Zhang HY, Chen K, Zhang Y, et al. Preoperative nutritional support in children with Hirschsprung disease: a prospective multicenter open-label randomized controlled trial. Nat Commun. 2025;16(1):11171. doi:10.1038/s41467-025-66541-x.
- Frykman PK, Short SS. Hirschsprung-associated enterocolitis: prevention and therapy. Semin Pediatr Surg. 2012;21(4):328-335.
- Gosain A, et al. Guidelines for the management of Hirschsprung-associated enterocolitis. American Pediatric Surgical Association. 2017.