Rate of postoperative weight gain and clinical outcomes in patients undergoing surgery for necrotizing enterocolitis

Introduction

Necrotizing enterocolitis (NEC) is an acute necrotizing intestinal disease that greatly affects the lives of neonates, particularly premature infants. In recent years, advances in perinatal medicine and neonatal critical care have led to an increase in the birth rate of very low and ultra-low birth weight (BW) neonates, as well as improved treatment success rates (1). NEC is a severe disease with a high mortality rate, with an overall mortality rate of approximately 10–50% (2). In severe cases requiring surgical intervention, the mortality rate may reach 50% or higher (2). Further, NEC may lead to long-term complications, including growth retardation and neurodevelopmental abnormalities (3,4).

To date, there is no specific treatment for NEC; however, 60–80% of neonates with NEC recover through conservative medical treatment, including holding feeds, gastrointestinal decompression, anti-infective treatments, and other comprehensive therapeutic measures (2). Around 20–40% of neonates with severe NEC undergo surgical treatment (5,6). The mortality rate of neonates with NEC who require surgical treatment is higher than that of those who receive conservative medical management, and survivors frequently experience postoperative complications, including malnutrition, intestinal stricture, intestinal obstruction, short bowel syndrome (SBS), and intestinal failure associated liver disease (IFALD). In the long term, NEC patients who require surgical treatment are also at a higher risk of growth restriction and neurological abnormalities (7,8).

Due to the modified anatomy and physiology of the intestinal tract, patients who undergo surgery for NEC are more susceptible to malnutrition and imbalances in water and electrolyte homeostasis. This homeostasis imbalance affects the rate of weight gain in infants with NEC. The key to early postoperative treatment in infants with NEC is to maintain the water and electrolyte balance. The early initiation of microfeeding and parenteral nutrition support is crucial to provide adequate calorie and nutrient intake, establish a favorable nitrogen balance, prevent substantial weight loss, reduce complications, and enhance the prognosis of affected infants (9). Further studies need to be conducted to investigate the effect of the postoperative weight gain rate on the clinical outcomes of surgical NEC infant patients, and to establish relevant clinical standards. This study aimed to explore the effects of postoperative nutritional management on the rate of weight gain in NEC infants, and its association with short-term clinical outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-418/rc).

Methods

Study design and population

This retrospective study was conducted at the Children’s Hospital of Soochow University, which is a specialist tertiary pediatric hospital in East China. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Children’s Hospital of Soochow University (No. 2022CS009), and the requirement of individual consent for this retrospective analysis was waived.

In this study, we retrospectively collected and analyzed the clinical data of neonates who underwent surgery for NEC between 2014 and 2022. Patients were included in the study if they survived the surgery and were discharged. Patients were excluded from the study if they met any of the following exclusion criteria: had congenital gastrointestinal malformations, underwent gastrointestinal surgery for conditions other than NEC, had spontaneous intestinal perforation without evidence of NEC, had genetic metabolic disorders, had chromosomal abnormalities, and/or lacked complete clinical data. Ultimately, a total of 80 patients
who underwent NEC surgery were included in the study.

The diagnosis of NEC was based on the modified Bell staging criteria (10). The surgical care followed standards for infants with NEC. Absolute indications for surgery included evidence of intestinal perforation and positive findings of perforating fluid. Relative indications for surgery included ineffective conservative medical treatment or disease progression (11). In the surgical evaluation of NEC, ultrasound imaging was used to assess the abdominal lesions and to assist surgeons to determine the surgical indications.

According to the “Recommendations for Feeding Preterm and Low-Birth-Weight Infants After Hospital Discharge” (12), which define intrauterine growth velocity as 10–20 g/(kg·d), the surviving neonates were classified into the following two groups based on the postoperative weight gain rate: the low rate of weight gain (LRWG) group [<10 g/(kg·d)] and the high rate of weight gain (HRWG) group [≥10 g/(kg·d)]. The rate of weight gain was calculated as follows: rate of weight gain [g/(kg·d)] = [1,000 × (Wt’ − Wt)]/(N × Wt’), where Wt’ represents the body weight at discharge (in kg), Wt represents the body weight at the time of surgery (in kg), and N represents the duration from surgery to hospital discharge (in days). Standardized feeding and nutritional management protocols were followed for the neonates, with individualized adjustments made according to their specific clinical conditions. In accordance with clinical practice and neonatal care guidelines, this study used 20% soya oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) lipid emulsion to provide appropriate energy and essential fatty acids to the infants.

Clinical data

The clinical data of the infants in the LRWG and HRWG groups were collected (see Table S1), including patient demographics, presence of intestinal perforation, length of resected intestinal segments, preservation of the ileocecal valve, presence of intestinal fistula, time to the initiation of breast milk feeding postoperatively, time to full enteral feeding (EF), fluid and caloric intake in the first and second postoperative weeks, duration of respiratory support, antibiotic administration, and the presence or absence of comorbidities such as IFALD, sepsis, central infections, respiratory failure, infective shock, renal impairment, hepatic injury, intestinal obstruction, intestinal stricture, and SBS. All comorbidities were diagnosed using the diagnostic criteria outlined in Practical Neonatology (13). All the diagnoses in this study were jointly evaluated by two neonatologists; If any disagreements arose, a third neonatologist was consulted.

Physical and neurodevelopmental assessment

The World Health Organization’s (WHO’s) Anthro software (v3.0.1; 2009) was used to calculate the length-for-age Z-score (LAZ), weight-for-age Z-score (WAZ), and head circumference-for-age Z-score (HcAZ) of each child with NEC. Developmental delay was defined as the presence of at least one indicator (WAZ, LAZ, or HcAZ) measuring more than two standard deviations (SDs) below the mean (14). Neurobehavioral development in the early stages was evaluated using the Neonatal Behavioral Neurological Assessment (NBNA) score, which has a total possible score of 40. An abnormal result was defined as a score below 35 (15). The growth and development of the patients were evaluated using the Gesell development scale (revised by the Healthcare Institute of Beijing Children’s Hospital). The results were reported as the developmental quotient, with scores ≥86 considered average, scores ranging from 76 to 85 considered borderline, and scores <75 considered abnormal (16). The medical staff received standardized professional training. The examination environment was characterized by quietness, a suitable room temperature, bright lighting, and a simple yet comfortable layout. Before commencing the tests, the medical staff showed kindness and established a positive rapport with the children to help alleviate any anxiety or fear, and allow them to acclimate to the examination environment.

Statistical analysis

The statistical analysis was performed using IBM SPSS Statistics software (v26.0). The normality of the measurement data was assessed using the Kolmogorov-Smirnov test, while variance homogeneity was evaluated using the Levene test. The normally distributed data are presented as the mean ± SD, and comparisons between two groups were performed using the independent sample t-test. The non-normally distributed data are expressed as the median (25^th, 75^th percentile) [M (P25, P75)], and comparisons between two groups were performed using the Mann-Whitney U test. The count data are presented as the number of cases (%), and comparisons between two groups were performed using the Chi-squared test (n≥40, T ≥5), or the continuity-corrected Chi-squared test (n≥40, 1≤ Tmin <5). A P value <0.05 was considered statistically significant. Logistic regression was used to evaluate the independent risk factors of the NEC patients with a LRWG.

Results

Baseline characteristics and intraoperative conditions

From January 1, 2014, to December 31, 2022, a total of 36,693 neonatal discharges were recorded at our hospital. Among these patients, 357 had NEC, resulting in an incidence rate of 0.97%. Among the 357 NEC patients, 104 underwent surgical treatment for NEC, resulting in a surgical rate of 29.13%. Of the 104 infants who underwent surgery for NEC, 25 (24.04%) were transferred from external hospitals, and had an average age of 16.81±4.11 days at the time of transfer. Additionally, of the 104 infants who underwent surgery for NEC, 6 (5.77%) had a gestational age (GA) of <28 weeks, 53 (50.96%) had a GA of 28 to 31⁺⁶ weeks, 33 (31.73%) had a GA of 32 to 36⁺⁶ weeks, and 12 (11.54%) had a GA of ≥37 weeks. Unfortunately, 24 infants succumbed to complications related to the surgery, resulting in a mortality rate of 23.08%. Ultimately, 80 surviving infants who had undergone surgery for NEC were enrolled in the study.

Among the 80 surviving infants who underwent NEC surgery, the average rate of postoperative weight gain was 8.02±6.27 g/(kg·d). This group was further categorized into two subgroups based on their rate of weight gain: the LRWG group (comprising 45 infants) and the HRWG group (comprising 35 infants). A total of 54 patients (67.5%) underwent enterostomies, including 36 in the LRWG group and 26 in the HRWG group. Among these patients, there were approximately an equal number of males (n=42) and females (n=38). The BWs of the patients ranged from 930 to 3,700 g (mean ± SD: 1.94±0.70 kg). The GAs of the patients ranged from 27.28 to 39 weeks (mean ± SD: 32.40±3.14 weeks). At hospital discharge, the mean weight of the patients was 2.67±0.46 kg.

No significant differences were observed between the two groups in terms of gender, GA, BW, small for GA, mode of delivery, presence of twins or multiple births, corrected GA at discharge, and corrected GA at discharge exceeding 40 weeks (P>0.05). However, the BW at discharge was lower in the LRWG group than the HRWG group. Additionally, the incidence of extrauterine growth restriction (EUGR) was significantly higher in the LRWG group than the HRWG group (P<0.05). There were no significant differences between the two groups in terms of the preservation of the ileocecal valve and the presence of perforation (P>0.05). However, the proportion of patients who underwent enterostomy was higher in the LRWG group than the HRWG group. Further, the proximal intestinal length was significantly shorter in the LRWG group than the HRWG group (P<0.05). For further information, see Table 1.

There were no significant differences between the two groups in terms of BW regain at the time of surgery, the rate of weight gain from surgery to before feeding, and the rate of weight gain in the first postoperative week (P>0.05). The time to regain preoperative weight after surgery and the time to postoperative weight loss was greater in the LRWG group than the HRWG group (P<0.05). The percentage of weight loss after surgery, the rate of weight gain from initiation of feeding to hospital discharge, and the rate of weight gain in the second postoperative week were lower in the LRWG group than the HRWG group (P<0.05). For further information, see Table 1.

Postoperative enteral nutrition

There was no statistically significant difference between the two groups in terms of the time of EF initiation (P>0.05). Conversely, the LRWG group exhibited a longer time to reach half EF, full EF, and oral caloric intake of 120 kcal/kg·d compared to the HRWG group (P<0.05). Moreover, during the first postoperative week, the LRWG group had a lower intake of fat emulsion per day than the HRWG group (P<0.05). However, no significant differences were found between the two groups in terms of the average daily intake of amino acids, calories, and fluids during the first and second postoperative weeks. For further information, see Table 2.

Postoperative treatment and complications

The LRWG group had a prolonged duration of postoperative antibiotic usage compared to the HRWG group. Additionally, the proportion of patients with postoperative sepsis after NEC surgery was higher in the LRWG group than the HRWG group (P<0.05). However, no significant differences were observed between the two groups in terms of postoperative ventilator duration, occurrence of complications such as IFALD, central nervous system (CNS) infection, respiratory failure, sepsis shock, renal insufficiency, hepatic insufficiency, ileus, intestinal stricture, and SBS (P>0.05). For further information, see Table 3.

Risk factors for a LRWG in preterm infants with NEC postoperatively

A regular logistic regression analysis was performed on the variables that differed significantly between the two groups that were also of clinical relevance. The length of the proximal remaining bowel [odds ratio (OR) =0.768; 95% confidence interval (CI): 0.602–0.980; P=0.03], time to reach full EF (OR =1.131; 95% CI: 1.009–1.268; P=0.03), and duration of postoperative antibiotics (OR =1.140; 95% CI: 1.046–1.243; P=0.003) were identified as risk factors for a LRWG in preterm infants with NEC postoperatively (see Table 4).

Clinical outcomes

Of the 80 patients who survived and were discharged from the hospital, five were lost to follow-up due to changes in contact information and address, three died after discharge, one was diagnosed with cerebral palsy, and no children with visual or hearing impairments were identified. Sixty patients in both groups completed the NBNA examination at 40 weeks of corrected GA, including 33 patients in the LRWG group and 27 in the HRWG group. The NBNA scores of the LRWG group were significantly lower than those of the HRWG group (P<0.05). For further information, see Table 5.

In the population that completed follow-up at the corrected ages of 1–3 months, the scores for the WAZ, LAZ, HcAZ, fine motor skills, language proficiency, and ability to respond to materials and people were lower in the LRWG group than the HRWG group (P<0.05), but no significant difference was observed between the two groups in terms of gross motor skills (P>0.05). In the populations that completed follow-up at the corrected ages of 4–6 and 7–12 months, the scores for the WAZ, LAZ, HcAZ, fine motor skills, and the ability to respond to materials and people were lower in the LRWG group than the HRWG group (P<0.05), but no significant differences were found between the two groups in terms of gross motor skills and language proficiency (P>0.05). In the population that completed follow-up at the corrected age of 13–24 months, the scores for the WAZ, HcAZ, and ability to respond to materials and people were lower in the LRWG group than the HRWG group (P<0.05), but no significant differences were found between the two groups in terms of gross motor skills, fine motor skills, language proficiency, and the LAZ (P>0.05). For further information, see Table 5.

Discussion

This retrospective study was conducted at a tertiary pediatric hospital in East China. At our clinical center, the percentage of NEC infants who underwent surgery was 29.13%, while the mortality rate was 23.08%. Previous retrospective studies have reported that approximately 20–60% of infants with NEC require surgical intervention, and that the mortality rate among those who undergo surgery ranges from 37.2% to 43.8% (5,17,18). The prevalence of surgical NEC patients at our clinical center is in line with international reports, but the postoperative mortality rate of NEC patients undergoing surgery was relatively low.

Infancy represents the initial peak stage of growth and development, and is characterized by substantial nutritional requirements. However, most infants with NEC who undergo surgery experience a disruption in intestinal continuity. This leads to excessive loss of small intestinal villi, subsequently reducing the effective absorption area and impairing the absorption capacity for numerous nutrients. Affected children experience slow weight gain, and prolonged hospitalization, and their prognosis is directly linked to these factors (5). In our study, the incidence of postoperative EUGR after NEC was found to be remarkably high at 86.25%. This emphasizes a clear association between postoperative weight gain and clinical regression in children with NEC. Thus, it is crucial to ensure adequate nutritional support and closely monitor the growth of patients with NEC postoperatively. Prematurity and a low BW are typically associated with a LRWG; however, no significant differences were found in the BW and GA between the LRWG and HRWG groups in this study. Thus, in this population, the LRWG appeared to be closely related to factors such as postoperative management, infection control, intestinal recovery, and individualized nutritional support strategies.

In our study, the patients in the LRWG group had a shorter length of bowel retention, a higher proportion of enterostomy, a higher proportion of sepsis, and a longer duration of antibiotics compared to those in the HRWG group, which suggests that the degree of intestinal necrosis and inflammatory response were more severe in the LRWG group, and were directly related to the patients’ postoperative weight gain and prognosis. The prolonged duration of postoperative antibiotic use in the LRWG group was primarily due to clinical instability and higher sepsis rates, requiring extended treatment beyond the usual 14–21 days. This was not part of a standardized protocol but rather a clinical decision based on individual patient needs. However, prolonged antibiotic use may increase the risk of adverse effects such as antibiotic resistance and gut microbiota disruption, which should be carefully considered in clinical practice.

Mansour et al. (17) reported that 38% of infants experienced malnutrition, with 35% exhibiting severe malnutrition following enterostomy. Ng et al. (19) found that patients with jejunal stoma, even those who did not undergo small bowel resection, experienced significant weight loss, a decreased body mass index, and decreased bone mineral density postoperatively, and some developed electrolyte disorders. This may be related to postoperative complications such as impaired intestinal motility, enzyme deficiency, abnormal intestinal mucosa, infection and antibiotic use-induced flora disorders, reduced intestinal length, and subsequent vitamin B12 deficiency after ileocecal resection, which could affect patients’ postoperative physical growth and development. Recent studies have shown that the complete resection of necrotic intestinal tissue significantly improves survival in patients who require surgery for NEC (20). Thus, it is critical to minimize the loss of normal bowel while ensuring the complete removal of necrotic bowel tissue.

Infants with NEC undergoing enterostomy are expected to absorb fewer calories through enteral nutrition compared to healthy infants, with significant individual variation observed (21). Therefore, in practical terms, the actual supply of parenteral nutrition should be higher than the calculated amount to ensure good weight gain (22). In this study, no significant differences were observed in the postoperative caloric and fluid intake between the infants in the LRWG and HRWG groups. However, a statistically significant difference was observed in the fat emulsion intake during the first week after surgery between the groups. The infants in the HRWG group achieved half EF, full EF, and oral caloric intake of 120 kcal/kg·d significantly faster than those in the LRWG group. Notably, a longer time to reach full EF is a risk factor for a LRWG in preterm infants with NEC postoperatively. These findings suggest that the rate of weight gain in patients with the same fluid intake and calorie supply is associated with the early achievement of EF. Therefore, under the same fluid intake and calorie supply, reaching EF and the rate of weight gain may be related. The HRWG group achieved EF more quickly than the LRWG group, which may be related to the lower degree of intestinal necrosis and inflammatory response, and the longer length of the proximal remaining bowel. In the clinical management process, various factors affect the progress of EF. During the postoperative nutritional management process of NEC patients, clinicians should implement individualized management strategies, assess each patient’s general status, weight gain, blood gases, electrolytes, and stoma losses, and increase enteral nutrition in a timely manner after the patient has established tolerance to improve patient prognosis.

The current study revealed that 10% of the NEC infants who underwent surgery continued to exhibit delayed physical development at the corrected GA of 13–24 months. Specifically, the LRWG group consistently lagged behind the HRWG across all ages. These findings imply that a slower rate of weight gain during the early postoperative period may lead to long-term delays in physical development. Notably, these results align with previous national and international research studies (23,24).

In addition to physical developmental delays, neurodevelopmental disorders have been identified as complications in NEC patients (25). Research has shown that the neurological development of children with NEC lags significantly behind that of their typically developing peers. These children are at an increased risk of cerebral palsy, visual impairments, cognitive deficits, and psychological challenges. Further, it has been observed that the neurological prognosis of children who undergo surgery is worse (4,24,26).

In our study, a significant proportion of the children (82.35%) exhibited neurological developmental delays at the corrected age of 1–3 months. Postoperatively, in comparison to the HRWG group, the LRWG group demonstrated delays in fine motor skills, responsiveness, verbal communication, and overall development. These findings suggest the presence of varying degrees of early life neurodevelopmental delays. However, improvements were observed in the corrected GA of 13–24 months, although some children (10%) still experienced lingering delays, primarily in their ability to respond to materials and people.

This phenomenon can be attributed to the rapid development phase of the CNS during late pregnancy and early postnatal life. Adequate nutrient absorption is essential during this period as malnutrition and imbalance can disrupt energy metabolism in neurons and glial cells. A lower rate of body weight gain can lead to slower brain mass growth, a reduction in the neuronal count, decreased dendritic connectivity, and a diminished brain volume. Ultimately, these factors can affect children’s behavioral and cognitive abilities, and contribute to poorer neurological developmental outcomes (27,28).

This had a number of limitations. It was a single-center retrospective study with a small sample size. Future research should involve multi-center, large-scale clinical studies. Additionally, as the postoperative weight gain of NEC children is irregular, classifying them into HRWG and LRWG groups based on weight gain rate might have introduced bias in the groupings, which might have affected the outcomes.

Conclusions

Our findings suggest that the length of the remaining proximal bowel, the duration of postoperative antibiotics, and the time to reach full EF are significant risk factors for a LRWG in preterm infants with NEC postoperatively. A LRWG postoperatively can severely affect both the physical and CNS development of these infants in the long term. To improve outcomes in the future, bowel anastomosis should be considered whenever feasible to maximize intestinal length preservation. If intestinal resection is necessary, ensuring the complete removal of necrotic tissue while preserving as much healthy bowel as possible is crucial for optimizing nutritional absorption and growth. Additionally, precise and individualized nutritional support strategies, aimed at achieving full EF as quickly as possible, are essential in improving the long-term outcomes of NEC patients.

Acknowledgments

We thank all the children and their guardians who participated in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-418/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-418/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-418/prf

Funding: This work was supported by the National Natural Science Foundation of China (No. 82271741) and the Jiangsu Provincial Health and Family Planning Commission Medical Research Project (No. ZD2021013).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-418/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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Children’s Hospital of Soochow University (No. 2022CS009) and individual consent for this retrospective analysis was waived.

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/.

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(English Language Editor: L. Huleatt)