Hirschsprung disease (HSCR) is characterized by the complete absence of neuronal ganglion cells in a segment of the intestinal tract, most commonly in the large intestine (1). At present, surgery remains the primary effective treatment option for patients with HSCR, with the aganglionic section being removed. Hirschsprung-associated enterocolitis (HAEC) is a prevalent and severe complication after radical surgery for HSCR, which can lead to bowel obstruction and sepsis, with a high mortality rate (2). The typical clinical features of HAEC include explosive diarrhea, abdominal distension, fever, lethargy and vomiting. However, these symptoms are non-specific and can be similar to those of other diseases like gastroenteritis, which makes it difficult to identify HAEC in clinical practice and may lead to delayed treatment (3).

Although all patients diagnosed with HSCR are theoretically at risk of developing HAEC, a variety of factors have been identified that contribute to an elevated risk of this complication. These include family history of HSCR, trisomy-21, long-segment aganglionosis, delayed diagnosis, anastomotic leaks or strictures and prior episodes of HAEC (4–12). In addition, intestinal dysbiosis, macrophage infiltration, and neuroimmune abnormalities collectively promote the occurrence of HAEC (5, 13–15). Despite the identification of multiplerisk factors for HAEC, a predictive model for postoperative HAEC has not yet been established. Accordingly, we developed the first nomogram to predict the incidence of HAEC.

HAEC is a serious complication and significant cause of mortality among patients after operation for HSCR (18). Previous studies reported an incidence of postoperative HAEC ranging from 17% to 50% (3, 19, 20). In our study, the prevalence of HAEC was 26%, which is consistent with previous reports. The etiology and pathogenesis of HAEC are still unclear, the diagnosis of HAEC relies on clinical manifestations and symptoms which are often non-specific, making it difficult to establish a definitive diagnosis in many patients (21). In 2009, Pastor (16) proposed a scoring system for the clinical diagnosis of HAEC, which combines clinical, laboratory, and radiological parameters. They use a HAEC score of 10 or greater indicated diagnosis of HAEC. In 2018, Frykman (17) conducted an evaluation involving 116 children diagnosed with HSCR and posited that when the HAEC score was set at 4 or greater, the sum of sensitivity (83.7%) and specificity (98.6%) was optimal. Despite the HAEC scoring system's recent surge in popularity as a diagnostic tool, it is imperative to acknowledge its primary function as a diagnostic instrument rather than a predictive one. The purpose of this study is to construct a prediction model of HAEC for early detection of HAEC.

In recent years, research has identified a variety of risk factors associated with the development of HAEC. However, no studies have demonstrated a significant correlation between factors such as gender, age, preoperative hypoalbuminemia, and surgical method and the occurrence of HAEC (22, 23). In this study, we found the risk factors for HAEC include postoperative HAEC, long-segment or total colonic aganglionosis, and anastomotic leaks or strictures. Preoperative bowel preparation is a protective factor for postoperative HAEC.

We defined aganglionosis from the sigmoid colon onward as long segment and aganglionosis from the whole colon as total colonic aganglionosis (1). Previous studies have found that long-segment and total colonic aganglionosis are risk factors for HAEC (5, 24–26). A widely acknowledged predictor, long-segment have been proved to increase risk of postoperative HAEC by several studies (5). In terms of pathogenesis, long-segment and total colonic aganglionosis may lead to more severe intestinal motility and stasis due to a wider range of enteric nervous system dysfunction, which may lead to an increased risk of bacterial retention, overgrowth and translocation. This series of changes may contribute to the development of HAEC. Preoperative HAEC indicates that the intestine is already in an inflammatory state, and the intestinal barrier function, microbiota balance and immune state may have been impaired. In children with preoperative HAEC, there is an elevation in the quantity of Candida within the feces, concurrent with a reduction in the numbers of Malassezia and yeast (13). All of these factors augment the probability of postoperative recurrence of HAEC, thereby subjecting the postoperative intestine to an elevated risk of inflammation. The history of preoperative HAEC may persistently influence the incidence of postoperative HAEC (11). Intestinal flora translocation, macrophage phenotypic imbalance, and neuroimmune regulatory dysfunction collectively contribute to the pathogenesis of HAEC via intricate interactions. Postoperative intestinal motility disorders in HSCR lead to fecal stasis, which triggers dysbiosis, impairs the integrity of the intestinal barrier, and induces intestinal inflammation (13). The infiltration of M1-type macrophages increases in the lesioned intestinal segments (14). Neuroimmune regulatory disorders further amplify the inflammatory effect (15).

Anastomotic stenosis represents the primary etiological factor for intestinal obstruction subsequent to HSCR. Mechanical intestinal obstruction resulting from anastomotic complications will remarkably augment the risk of postoperative HAEC (7). Anastomotic leaks significantly elevates the risk and severity of postoperative HAEC through disrupting the intestinal barrier, facilitating bacterial translocation, and triggering chronic inflammation, thus emerging as a critical adverse prognostic factor warranting focused clinical surveillance (11, 27). Preoperative rectal irrigation preparation to alleviate mechanical intestinal obstruction can decrease the incidence of HAEC (28). In 2017, a guideline in the United States proposed that routine rectal washouts should be considered a preventative effective measure for HAEC (3). For prophylactic prevention of HAEC, some have advocated for routine rectal washouts in select populations (29). In addition, routine anal dilation within 2 weeks postoperatively and continue for three months can decrease the incidence of HAEC (30). However, there are also questions about the necessity of daily anal dilation. A study found daily dilation by family members to have similar efficacy to weekly dilations by medical staff with similar rates of HAEC (31). Antibiotics are a mainstay of treatment for HAEC, early administration of antibiotics to prevent disease progression should be considered in clinical suspicion of HAEC. Metronidazole is the most commonly used agent and should be instituted even if patients are manifesting mild symptoms (32). A prospective randomized trial found that 4 weeks of probiotic therapy reduced the incidence and severity of HAEC, but more research is needed to further determine its effectiveness in preventing HAEC (33).

Nomogram is a simple visual clinical prediction model. In this study, the AUC of the ROC curve is 0.79, indicating that the nomogram has a great performance in predicting postoperative HAEC. The calibration curve is relatively evenly distributed around the ideal line, indicating great consistency between the nomogram's predictions and the actual results. However, this study has several limitations. First, this study was of a small sample size and was conducted at a single- centre. Second, Most of the risk factors such as preoperative bowel preparation and preoperative HAEC, were hypothetical and have not been confirmed on a scientific basis. We expect to evaluate the performance of this nomogram through prospective external validation and provide treatment guidance for patients with HAEC.

In this study, the risk factors for postoperative HAEC were selected by multivariate analysis, and a nomogram was constructed to predict the possibility of HAEC. The nomogram has good predictive ability for HAEC, and may provide a reference for the need of postoperative preventive measures.