Early mortality of surgical treatments of necrotizing enterocolitis: experience of a tertiary neonatal intensive care unit (NICU) in Southwest China: a retrospective cohort study

Introduction

Neonatal necrotizing enterocolitis (NEC), a grave neonatal inflammatory bowel disorder, stands as the most prevalent and fatal gastrointestinal affliction among newborns. Despite an overall incidence rate approximating 1 in 1,000 live births, this figure escalates to 14% in infants weighing under 1,000 grams, with a concurrent rise in incidence rates concomitant with advancements in neonatal care for premature infants (1). While the majority of NEC cases are managed pharmacologically, 30% to 50% necessitate surgical intervention, carrying a mortality risk of 40% to 50% (2). Based on multicenter cohort studies in China, the overall mortality of NEC among preterm infants is 9.5%, with surgical NEC demonstrating a substantially higher mortality of 13.6%, while extremely preterm infants (<28 weeks) and those with birth weight 750–999 g exhibit mortality reaching 28.6% and 16.1%, respectively (3). Recent single-center investigations report a conservative favorable outcome rate of 78.5% following surgical intervention (4). Survivors often grapple with complications such as short-gut syndrome, dependency on total parenteral nutrition (PN), cholestatic liver disease linked to total PN, and neurodevelopmental delays, among others (5).

Population-level incidence data for NEC are often unreliable, primarily due to the non-specific presentation of milder forms of the disease. Severe NEC, however, is clinically characterized by symptoms indicative of ileus (abdominal distension, bilious aspirates/vomiting), intestinal inflammation (abdominal tenderness), and intestinal necrosis (bloody stools, bowel perforation). The definition of NEC has evolved over time, initially proposed by Bell et al. and subsequently refined by Walsh et al. (6). While definitions have varied across studies, they commonly incorporate Bell’s staging system (stages 1–3, based on a combination of clinical and radiological features) and confirmation through laparotomy. The management of definitive NEC necessitates either medical or surgical intervention, contingent upon the clinical presentation. Medical management typically encompasses abdominal decompression, bowel rest, broad-spectrum intravenous antibiotics, and intravenous hyperalimentation. Surgical intervention is indicated in cases of intestinal perforation or clinical deterioration despite maximal medical management (7).

Surgical intervention is required in 30–50% of NEC cases, with intestinal perforation being the only universally accepted absolute indication, while other indications remain controversial and largely dependent on surgeon experience, leading to significant practice variability and outcome heterogeneity. Delayed surgery due to failed medical management is associated with the poorest outcomes, as infants requiring surgery after failed conservative treatment had significantly longer time to surgery (69.3 vs. 23.5 hours for perforation) and the highest odds of death or PN requirement at 28 days post-surgery [odds ratio (OR) =4.54, 95% confidence interval (CI): 1.59–13.0] (8). Earlier surgical intervention in infants with suspected necrotic bowel without perforation may improve outcomes, though current evidence remains insufficient to establish definitive optimal timing, as a systematic review found no statistically significant association between timing of surgery and mortality, PN use, or neurodevelopmental outcomes in the limited available studies (9). Clinical prediction models combining hypothermia, absent bowel sounds, abnormal white blood cell count (WBC), C-reactive protein (CRP) >50 mg/L, pneumatosis intestinalis, and ascites [area under curve (AUC) >0.8] can help identify high-risk infants earlier, potentially enabling timely surgical intervention before clinical deterioration and improving outcomes in this vulnerable population (10).

In the surgical management of damaged intestine, the primary objective for surgeons is source control, involving the removal of clearly necrotic bowel segments. However, the postoperative period is associated with high morbidity, with reported complication rates ranging from 40% to 70% (11). A prior retrospective clinical study elucidated the predictors of postoperative mortality in surgical NEC cases (12). It was reported that 42.2% (38/89) of infants with surgical NEC succumbed, with key determinants including gestational age, birth weight, age of NEC onset, and the length of resected bowel. However, a notable limitation of this study lies in its temporal scope, spanning from 2000 to 2015. Given the rapid advancements in medical science, the treatment paradigms for NEC have evolved substantially over the past two decades. It is interesting that high-level, high-volume hospitals have demonstrated the lowest risk-adjusted mortality rates (13), with a consistent trend towards the decentralization of NEC care, with mortality rates varying in accordance with the level of care provided. Therefore, we have comprehensively evaluated the early mortality among newborns undergoing surgical treatment for NEC, aiming to early detection, timely treatment and reduction of mortality. Current predictive models, such as the nomograms developed by Shi et al, enable to early identify the high-risk infants for timely intervention, with the high sensitivity (90.5%) and specificity (80.9%) (10). However, small sample sizes with low event-to-predictor ratios (e.g., 21 events for 5 variables) raising concerns about overfitting and limited generalizability across diverse healthcare settings, and there is no unified conclusion on the key factors affecting the postoperative death of NEC (14). So more research is urgently needed to analyze the risk factors of infants who died after NEC operation to early detection, timely treatment and reduction of mortality.

In this study, we conducted a retrospective review of medical records spanning six years [2017–2023] to analyze the characteristics of neonates who underwent surgical treatment for NEC at our institution, with a specific focus on identifying risk factors associated with early postoperative mortality. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-824/rc).

Methods

Patients

This retrospective study was conducted by systematically reviewing the medical records of infants in the Neonatal Intensive Care Unit (NICU) at the Children’s Hospital of Chongqing Medical University from January 1, 2017, to July 31, 2023. The study protocol was approved by the Institutional Review Board (IRB) of Children’s Hospital of Chongqing Medical University (IRB No. CHCMU2023-244). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The requirement for written informed consent was waived because of the retrospective design.

Newborns diagnosed with NEC who underwent relevant surgical procedures within the specified time frame were eligible for inclusion in this study. Data on neonates with confirmed surgical NEC were retrieved from the electronic medical record system of the Children’s Hospital of Chongqing Medical University. The surgical interventions for patients encompassed surgical resection of the perforated and necrotic intestines, creation of intestinal stomas, and/or peritoneal drainage. A total of 181 patients underwent at least one operation for NEC and met the inclusion criteria, thus being enrolled in the study. The NEC surgery was performed by the same surgical team to avoid selection bias or surgical decision-making bias caused by different teams of surgeons.

Data collection

Clinical information of the selected infants was collected from the electronic medical record system. This information included pre-birth data within 24 hours after birth, such as gestational age, birth weight, sex, assisted reproduction status, Apgar score, the day of enteral nutrition were initiated, the actual start time of enteral feeding, weight of discharge, and length of hospital stay. Maternal perinatal information, including maternal age, mode of delivery (cesarean section), presence of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), pregnancy-induced anemia, antenatal interventions (pregnancy hormones, antibiotics), amniotic contamination, and premature rupture of membranes (PROM), was also collected. Characteristics of NEC infants prior to surgery, such as the age of NEC onset, weight of NEC onset, enteral nutrition of NEC onset, vomiting, bloody stools, fever, absent or diminished bowel sounds, abdominal redness, abdominal vein distension, pneumoperitoneum, and dyspnea, were documented. The examinations of the infants with NEC were performed by our NICU-based providers, including neonatology attendings, neonatology fellows, nurse practitioners. Additionally, laboratory test results before NEC surgery, including WBC, platelet count (PLT), hemoglobin (Hb), CRP, procalcitonin (PCT), blood glucose levels, and albumin levels, were recorded.

The diagnosis of NEC in newborns was made based on a combination of clinical and radiological examination findings. Currently, there is no definitive or curative treatment for NEC. Therapy is mainly supportive, aiming to prevent further injury to the affected intestine. Common supportive measures include fasting, gastrointestinal decompression, and the use of antibiotics. The surgical indications for NEC within our team remained relatively consistent throughout the study period. Operative notes for all patients were thoroughly reviewed, and all relevant findings were accurately recorded. Details such as the duration of surgery, the location and extent of intestinal lesions, and the specific surgical methods employed were meticulously documented in the surgical record. According to the surgical findings, infants were excluded if they had a diagnosis of spontaneous intestinal perforation.

The primary outcome of this research was postoperative mortality. The deceased group consisted of infants who required ventilator-assisted ventilation upon discharge from the hospital, had a serious infection (characterized by a significant increase in one or more inflammatory indicators), or had a milk intake of less than 50% of the full enteral feeding amount (120 mL/kg/day). In our study, we followed up on every family that discontinued treatment. Only one child survived, with severe brain damage. For an infant to be considered in the recovery or discharge (survival) group, the following criteria needed to be met: no need for ventilator or oxygen support, requirement for more than 80% of enteral nutrition, and no use of antibiotics.

Statistical analysis

Descriptive, categorical data were summarized as frequencies (absolute and relative) and tested for differences using a Chi-squared test. Continuous data, when symmetric, were presented as means ± standard deviation, and if skewed, as median [interquartile range (IQR)]. Two groups with continuous, parametric data were compared using a Student’s t-test. If the data were non-parametric, we used the Mann-Whitney U test. Statistical analysis were done with the software programs STATA 18 (Stata Software, College Station, TX, USA). Statistical significance was accepted at a two-tailed value of P<0.05.

Results

During the study period, a total of 681 infants were diagnosed with NEC at the Children’s Hospital of Chongqing Medical University. Among these infants, 181 (26.6%) had NEC surgery recorded in their electronic medical records. Of the 181 infants who underwent surgery, 143 (79.0%) were discharged home, while 38 (21%) either died or had treatment terminated. Among the 38 infants who died, the majority (30; 79%) passed away within 7 days postoperatively. Seven (18.4%) died after 7 days, and only one (2.6%) survived, as confirmed by telephone follow-up.

Regarding maternal characteristics, no significant differences were found between the two groups in parameters such as maternal age, Cesarean section delivery, pregnancy-induced hypertension, pregnancy-induced anemia, GDM, pregnancy hormones, prenatal antibiotics, amniotic contamination, PROM, and premature rupture lasting more than 18 hours (premature rupture >18 h) (Table 1).

A comparative analysis of the characteristics of survivors and deceased neonates admission and perinatal period (Table 2). The difference in male gender, gestational age, birth weigh and the Apgar score at 1 minute were statistically significant between the two groups. In addition, Survivors also had a longer length of hospital stay compared to the deceased group. However, no significant differences were observed with respect to multiple gestation, assisted reproduction, Apgar scores at 5 minutes, Apgar scores at 10 minutes, age of admission, age of enteral nutrition, and enteral nutrition at admission.

A comparison of the clinical characteristics of NEC infants at the onset of the disease revealed no significant differences between the two groups in terms of age and the presence of enteral nutrition (Table 3). However, the weight of NEC onset was significantly higher in the survival group compared to the deceased group. Before surgery, there were no significant differences in clinical presentations such as vomiting, red abdomen, abdominal veins, pneumoperitoneum, and apnea between the two groups. However, survivors had a higher incidence of bloody stools [82 (57.3%) vs. 13 (34.2%); P=0.01] compared to those who died. In contrast, infants who died were more likely to present with fever (P=0.003), absent or diminished bowel sounds (P=0.004), and dyspnea (P=0.004) (Table 3). Significant differences were observed between the two groups in the prevalence of congenital heart disease (CHD) (P=0.01), shock (P<0.001), and the need for ventilator-assisted ventilation (P<0.001) before NEC surgery. No significant differences were found in other clinical characteristics such as septicemia, meningitis, or pulmonary hemorrhage (Table 3). Regarding treatment measures, no differences were observed in the use of red blood cell transfusions, probiotics, or antibiotic.

Statistical analysis of laboratory test results before NEC surgery revealed significant differences between the two groups (Table 4). The survival group had higher PLT and albumin levels compared to the deceased group and. On the contrary, the PCT level was significantly lower in the survival group compared to the deceased group. The proportion of infants with abnormal blood glucose levels was also significantly higher in the survival group compared to the deceased group. No significant differences were found in WBC, Hb, or CRP.

On multivariable logistic regression analysis only bloody stool, fever, shock and PCT before NEC surgery were associated with mortality after NEC surgery (Table 5). We excluded absent or diminished bowel sounds and dyspnea, due to their relatively subjective nature. Additionally, CHD [atrial septal defect, ventricular septal defect, patent ductus arteriosus (PDA)] was also excluded because the concept is relatively broad. Although PDA with significant left-to-right shunting may increase the risk of NEC, the presence of persistent PDA did not significantly influence the incidence of intestinal perforation in NEC among extremely low-birth-weight infants, with perforation rates of 44.4% in the PDA-persistent group versus 54.5% in the PDA-resolved group (P=0.65) (15). We excluded gender with relatively minimal impact on outcomes. We have also deleted the correlation analysis about length of hospital stay in the multivariate regression analysis, because it’s a classic case of survivor bias, where deceased patients naturally have shorter stays because their observation period was truncated.

Characteristics of deceased children

In our study, we followed up on every family that discontinued treatment. All the children who discontinued treatment died, with only one child surviving, accompanied by severe brain damage. Among the 38 deceased infants, 30 (79%) died within 1 week of surgery, and 7 (18.4%) died after 1 week, with only one (2.6%) surviving ultimately (Figure 1). At the time of discharge, 35 (92.1%) infants required ventilator assistance, while 3 (7.9%) were discharged without it.

Figure 1 Survival curve of postoperative treatment termination time. Postoperative time is day. CI, confidence interval.

Reasons for treatment termination in deceased group

The primary reasons for treatment termination were severe intestinal disease and severe infection. For instance, seven infants were discharged within 3 days of surgery due to extensive diseased bowel at the time of operation. Twelve infants received conservative treatment due to severe intestinal lesions during surgery. Major early complications after surgical management of NEC included stricture, abscess, dehiscence, wound healing problems, and recurrent disease. Among the deceased infants, four required a second operation for various reasons, such as pneumoperitoneum, anastomotic leakage, or persistent fecal drainage from abdominal drainage. Nine infants had poor treatment outcomes post-surgery due to severe infection, shock, capillary leakage syndrome, or the continued use of vasoactive drugs without stable vital signs. Additionally, grade IV intracranial hemorrhage, poor intestinal function recovery within half a month after surgery, severe bronchopulmonary dysplasia with identified genetic defects, and other factors contributed to early discharge. Only three infants were discharged without a definite reason, and one of them survived, as confirmed by telephone follow-up.

Discussion

NEC is one of the most common and devastating diseases in neonates. Several retrospective observational studies have delved into the demographics, comorbidities, and clinical outcomes of NEC. In this context, we conducted a comprehensive review of the clinical records of 181 infants with surgical NEC treated between 2017 and 2023, with a specific focus on analyzing the risk of mortality. The extent of bowel involvement emerged as the most critical factor influencing surgical decision-making, yet there remains a paucity of reports elucidating its association with NEC outcomes. Benjamin’s research indicated that surgical intervention carries a mortality risk ranging from 40% to 50%, with morbidity rates reaching up to 70% (1). Among our cohort, 21% (38/181) of infants with NEC surgery succumbed, a figure significantly lower than the mortality rate reported by Garg et al. (12). On multivariable logistic regression analysis bloody stools, fever, shock and PCT before NEC surgery were associated with mortality after NEC surgery. It’s interesting that fever was positively correlated with postoperative mortality, whereas bloody stool was negatively correlated with postoperative mortality, suggesting that the presence or absence of bloody stools in NEC patients cannot serve as a reliable prognostic indicator for predicting clinical outcomes. Among preterm infants presenting with bloody stool, NEC was the most common diagnosis (40%), followed by food-protein-induced proctocolitis (37.2%) and idiopathic neonatal transient colitis (20%), with lower gestational age being associated with higher NEC prevalence (16). In addition, it’s increased great concern about the effect of shock, as an index to evaluate systemic circulation of infant, on the mortality of the surgery babies. Shock was significantly associated with portal venous gas in NEC (19.7% vs. 6.5%, P=0.02), indicating that hemodynamic instability may serve as a critical clinical predictor of disease severity and adverse outcomes in preterm neonates with NEC (17). Similarly, Nolan et al. highlighted shock as a critical determinant of poor prognosis in NEC, because the article indicate that NEC can rapidly progress to shock and death despite timely recognition and treatment, about 30% of infants affected by NEC experiencing mortality or major disability (18).

In recent years, researchers have sought to identify objective biomarkers for NEC screening and diagnosis. Although no ideal biomarker has been discovered, our study identified trends associated with increased mortality. Specifically, a significantly higher proportion of deceased infants had elevated PCT levels prior to NEC compared to survivors. Wang et al. also found PCT to be an independent factor related to the need for surgical intervention in NEC (19). In addition, the PCT may be considered as the early biomarkers in the severity of NEC, because PCT was higher in severe group than in mild-moderate group in NEC infants (20), and Liebe et al. reported that PCT may serve as a potential indicator of disease progression risk (21). These findings indicated that elevated PCT levels correlate with mortality, surgical necessity, and disease progression in NEC, positioning PCT as a robust biomarker for risk stratification. These researches collectively suggest that PCT monitoring could enhance clinical decision-making by identifying high-risk infants requiring aggressive intervention. Future research should prioritize prospective multicenter studies to validate PCT cutoff thresholds across diverse populations and investigate its integration with other inflammatory markers to develop composite predictive models for personalized NEC management. Although infants who died were more likely to have lower PLT counts on the day of NEC diagnosis, consistent with the findings of Zhang et al. (22), and lower PLT has been identified as a potential indicator of bowel necrosis, associated with high mortality in NEC infants (23). However, multivariate regression analysis revealed no significant association between PLT and postoperative mortality in NEC.

Beyond the analysis of objective indicators, we further analyzed the characteristics of deceased infants post-surgery. Among the 38 deceased infants, 78.9% (30/38) died within one week of surgery due to various reasons. For instance, 19 infants discontinued treatment due to severe intestinal lesions, three required a second operation for different reasons, and eight experienced poor treatment outcomes post-surgery due to severe infection, shock, capillary leakage syndrome, or the continued use of vasoactive drugs without stable vital signs. Similarly, Nolan et al. reported that in patients with NEC following laparotomy, the primary cause of early postoperative death was pan-intestinal NEC (18). In reality, a systemic inflammatory response is anticipated postoperatively, and infants may require aggressive ventilatory and circulatory support as well as blood product transfusion. Clark et al. reported that two-thirds of these infants died within a week of diagnosis (with a median time of death being one day after diagnosis) (23), without analyzing the specific causes of death, nor did they report whether surgery was performed among the deceased children. Upon review of the surgical records, we observed that some infants who died within one week of surgery had documentation of severe intestinal pathology, because some families decided to discontinue operative intervention in favor of conservative management, with subsequent withdrawal of care shortly thereafter. To elucidate the underlying reasons for this phenomenon, we conducted a comprehensive analysis of contributing factors across multiple dimensions. Although the exceptional expertise and advanced clinical philosophy of the neonatal surgical team at Children’s Hospital of Chongqing Medical University, enable optimal decision on surgical timing and procedural strategies for NEC patients. and the neonatal diagnosis and treatment center, the largest NICU in western China, provide robust postoperative recovery support for NEC infants. However, the relatively lower income in Southwest China often leaves families unable to bear the prolonged ICU costs and multiple surgeries required for severe NEC cases. Traditional extended family decision-making structures in this region may prioritize collective family welfare over aggressive intervention for infants, especially in children who are likely to have a poor prognosis. The prevalence of rural, agrarian livelihoods with limited savings and no paid medical leave means families face catastrophic health expenditures that threaten the entire household’s survival, making treatment abandonment an economically rational choice. Although it’s a regrettable phenomenon, we hope that a greater proportion of affected infants will receive aggressive treatment, with continued improvements in economic conditions and evolving societal perspectives regarding neonatal recovery after treatment. In addition, the gestational age in survival group (34.2±3.6 weeks) was higher than that in death group (32.1±3.7 weeks), with a statistical significance (P=0.001), which might indicate that lower gestational age may correlate with more probability of decision to treatment discontinuation, as these neonates require prolonged recovery periods and greater financial resources for postoperative care.

Perforation serves as an absolute indication for surgical intervention, and the decision-making process in this regard has been identified as an area with significant potential for improving outcomes (24). It’s interesting that in the deceased group, non-perforated infants accounted for 65.8%, whereas perforated cases accounted for 34.2%, with this difference being statistically significant (data not shown). This finding suggests that more aggressive evaluation of additional indicators for early surgical intervention should be pursued, rather than relying on the presence of intestinal perforation. Pan-intestinal patients (those with disease affecting 75% or more of the bowel) treated with drainage are at a heightened risk of early mortality. Surgical management is predominantly guided by the individual surgeon’s clinical experience, with potential surgical indications including worsening abdominal girth over time, significant abdominal wall erythema, and the presence of a fixed abdominal mass. Early diagnosis and timely intervention are pivotal in reducing bowel loss and enhancing survival rates (25). Therefore, with our extensive surgical experience and comprehensively evaluating clinical characteristics, we would accurately determine the optimal timing and surgical approach, ensuring that intestinal lesions remain relatively localized at the time of surgical intervention, to decrease the morbidity.

A limitation of our study is the occurrence of infant withdrawal of support, which complicates the interpretation of the analysis of causes of death. For example, some infants with extensive and severe involvement may undergo an exploratory laparotomy without further surgical intervention due to parental refusal of additional surgery, resulting in withdrawal from treatment and discharge within one week of surgery. Although severe intestinal lesions increase the risk of death, some children may survive after aggressive surgical intervention. Future quality investigations are necessary to optimize the use of limited therapeutic resources. In addition, the mortality group comprised only 38 patients, whereas our multivariate regression analysis incorporated 12 variables (with subjective factors excluded, retaining only relatively objective indicators), which may compromise the reliability of our results. This limitation arises partly from the relatively low postoperative mortality rate in our NICU, resulting in a small mortality group sample size, and partly underscores the urgent need for further multicenter, large-volume studies to explore the risk factors for mortality of postoperative in neonates with NEC.

Conclusions

In summary, the primary cause of death in infants undergoing surgical treatment for NEC might be severe intestinal lesions. Our study underscores the complex interplay of factors contributing to NEC mortality, highlighting the need for continued research into biomarkers and surgical strategies to improve outcomes in this vulnerable patient population.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-824/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-824/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-824/prf

Funding: This study was supported by Jiangxi Provincial Natural Science Foundation (No. 20242BAB23079), Natural Science Foundation of Chongqing Municipality (No. CSTB2023NSCQ-MSX0178), and Medical Research Project of Chongqing Municipal Health Commission (No. 2025WSJK013).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-824/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Institutional Review Board of Children’s Hospital of Chongqing Medical University (IRB No. CHCMU2023-244), and the requirement for informed consent was waived because of the retrospective design. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Carr BD, Gadepalli SK. Does Surgical Management Alter Outcome in Necrotizing Enterocolitis? Clin Perinatol 2019;46:89-100.
2. Feng B, Zhang Z, Wei Q, et al. A prediction model for neonatal necrotizing enterocolitis in preterm and very low birth weight infants. Front Pediatr 2023;11:1242978.
3. Cao X, Zhang L, Jiang S, et al. Epidemiology of necrotizing enterocolitis in preterm infants in China: A multicenter cohort study from 2015 to 2018. J Pediatr Surg 2022;57:382-6.
4. Li JL, Wei H, Tan Q, et al. Comparative analysis of clinical characteristics of term and preterm neonates with necrotizing enterocolitis undergoing surgery. Zhongguo Dang Dai Er Ke Za Zhi 2025;27:595-600.
5. Xiong T, Maheshwari A, Neu J, et al. An Overview of Systematic Reviews of Randomized-Controlled Trials for Preventing Necrotizing Enterocolitis in Preterm Infants. Neonatology 2020;117:46-56.
6. Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986;33:179-201.
7. Kang C, Zhang R, Wang G, et al. Simple Scoring System that Predicts the Need for Surgical Intervention in Infants with Necrotizing Enterocolitis. Arch Med Res 2023;54:37-44.
8. Bethell GS, Knight M, Hall NJ, et al. Surgical necrotizing enterocolitis: Association between surgical indication, timing, and outcomes. J Pediatr Surg 2021;56:1785-90.
9. Duric B, Gray C, Alexander A, et al. Effect of time of diagnosis to surgery on outcome, including long-term neurodevelopmental outcome, in necrotizing enterocolitis. Pediatr Surg Int 2022;39:2.
10. Shi B, Shen L, Huang W, et al. A Nomogram for Predicting Surgical Timing in Neonates with Necrotizing Enterocolitis. J Clin Med 2023;12:3062.
11. Sato TT, Oldham KT. Abdominal drain placement versus laparotomy for necrotizing enterocolitis with perforation. Clin Perinatol 2004;31:577-89.
12. Garg PM, Hitt MM, Blackshear C, et al. Clinical determinants of postoperative outcomes in surgical necrotizing enterocolitis. J Perinatol 2020;40:1671-8.
13. Kastenberg ZJ, Lee HC, Profit J, et al. Effect of deregionalized care on mortality in very low-birth-weight infants with necrotizing enterocolitis. JAMA Pediatr 2015;169:26-32.
14. Wu Y, Ren H. Development of a predictive model for severe adverse outcomes following surgery for neonatal necrotizing enterocolitis: a nomogram study based on postoperative intestinal failure beyond 42 days and death. Front Pediatr 2025;13:1670493.
15. Muto M, Sugita K, Murakami M, et al. Association between gastrointestinal perforation and patent ductus arteriosus in extremely-low-birth-weight infants: a retrospective study of our decade-long experience. Pediatr Surg Int 2023;39:125.
16. D'Auria E, Cavigioli F, Acunzo M, et al. Food-Protein-Induced Proctocolitis in Pre-Term Newborns with Bloody Stools in a Neonatal Intensive Care Unit. Nutrients 2024;16:3036.
17. Lin X, Zeng HP, Fang YF, et al. Predictive Indicators for Necrotizing Enterocolitis With the Presence of Portal Venous Gas and Outcomes of Surgical Interventions. Front Pediatr 2021;9:683510.
18. Nolan LS, Wynn JL, Good M. Exploring Clinically-Relevant Experimental Models of Neonatal Shock and Necrotizing Enterocolitis. Shock 2020;53:596-604.
19. Wang Q, Jin K, Su X, et al. Predictive value of serum markers in the operation evaluation of neonatal necrotizing enterocolitis. Transl Pediatr 2023;12:897-906.
20. Meng W, Wang Q, Xu Q, et al. Biomarkers in the Severity of Necrotizing Enterocolitis in Preterm Infants: A Pilot Study. Int J Gen Med 2024;17:1017-23.
21. Liebe H, Lewis S, Loerke C, et al. A Retrospective Case Control Study Examining Procalcitonin as a Biomarker for Necrotizing Enterocolitis. Surg Infect (Larchmt) 2023;24:448-55.
22. Zhang Y, Ma JK, Wei H, et al. Predictive scores for mortality in full-term infants with necrotizing enterocolitis: experience of a tertiary hospital in Southwest China. World J Pediatr 2016;12:202-8.
23. Clark RH, Gordon P, Walker WM, et al. Characteristics of patients who die of necrotizing enterocolitis. J Perinatol 2012;32:199-204.
24. Bethell CS, Knight M, Hall NJ. Surgical necrotizing enterocolitis: Association between surgical indication, timing, and outcomes. J Pediatr Surg 2021;56:1785-90.
25. Chen J, Mu F, Gao K, et al. Value of abdominal ultrasonography in predicting intestinal resection for premature infants with necrotizing enterocolitis. BMC Gastroenterol 2022;22:524.