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Surgical experience with neonatal necrotizing enterocolitis (NNE).

Neonatal necrotizing enterocolitis, a highly lethal disorder of premature infants, is a common occurrence in newborn care units. This report details operative experience with 33 infants over the past seven years. During this time many more infants with NNE have recovered with supportive therapy. All patients are treated on a standard protocol of therapy and monitoring designed to select those with signs of continuing clinical deterioration. Therefore, those coming to operation had additional complications, such as perforation, intestinal gangrene or stenosis. This protocol is described. The 33 infants, averaging less than 4 lbs., developed NNE within five days of birth. Perforation and signs of continued clinical deterioration were the indications for operation; severe sepsis and clotting abnormalities were the rule. The overall mortality was 40% but included six infants with total bowel necrosis who had laparotomy alone. Five patients had intestinal or colonic resection with primary anastomosis, with two leaks leading to death. Twenty-one patients had staged resection with delayed anastomosis and only four deaths. Thus 27 determinative cases had a 26% mortality, and the recent group with staged resection had a 19% mortality. The essentials of pre-, intra- and postoperative management are detailed, as well as pathology and bacteriologic data. Most infants had temporary malabsorption requiring parenteral nutrition and special diets. Long-term results are gratifying.

Enterocolitis, Pseudomembranous↗

Preventing necrotizing enterocolitis in neonates.

Necrotizing enterocolitis of newborn infants virtually vanished from our nurseries during the four years since the introduction of a slowly progressive feeding regimen. This cautions approach to feeding has been applied to selected infants whose condition during labor and delivery or whose neonatal problems indicate that they are at risk.

Enteral Nutrition↗

Neonatal necrotizing enterocolitis: review and current concepts.

Necrotizing enterocolitis poses a serious threat to the increasing number of "at risk" neonates. Its clinical picture is characterized by abdominal distension, gastric retention, bile vomitus, and bloody stools. Abdominal roentgenograms demonstrate loops of intestine with intramural gas. Many of the neonates with necrotizing enterocolitis have been successfully managed by aggressive medical treatment. A review of the clinical course of 64 neonates with necrotizing enterocolitis in the acute phase suggests that either persistence of abdominal distention, development of edema and erythema of the abdominal wall, or pneumoperitoneum are indications for surgical intervention. Seven neonates presented with colonic stenosis several months after the management of the acute phase of necrotizing entercolitis.

Constriction, Pathologic↗

Regulation of hemodynamics and oxygenation in developing intestine: insight into the pathogenesis of necrotizing enterocolitis.

The pathogenesis of necrotizing enterocolitis remains unknown, but various factors have been postulated including, but not limited to, mesenteric ischemia, enteral alimentation, and infection. Since an understanding of circulatory physiology in developing intestine may provide insight into the role of mesenteric ischemia in the etiology of necrotizing enterocolitis, this review summarizes what is currently known about the regulation of blood flow and oxygenation in developing intestine and how it differs from that in adult intestine. The discussion is divided into intrinsic versus extrinsic factors. Phenomena which may be used to evaluate the capacity for intrinsic vasoregulation include pressure-flow autoregulation, reactive hyperemia, venous hypertension, arterial hypoxemia, and postprandial hyperemia. Extrinsic factors include neurologic and hormonal influences. Additionally, the susceptibility for tissue hypoxia as a function of age and the correlation with subsequent development of mucosal injury are discussed.

Cell Hypoxia↗

Importance of early ileostomy closure to prevent chronic salt and water losses after necrotizing enterocolitis.

Six infants with necrotizing enterocolitis were discharged after periods of prolonged hospitalization (two to nine months) with intact ileostomies. Their initial hospitalization was complicated by feeding difficulties, chronic diarrhea, sepsis, rickets, and developmental delay. All were rehospitalized within three months, with severe acidosis and dehydration after a presumed viral-type illness. Each had large-volume ileostomy output, which was rich in electrolytes and bicarbonate. A prolonged recovery phase (two to eight months) again was punctuated with episodes of diarrhea, problems in starting oral feeding, and sepsis. After reanastomosis of the remaining bowel, no infant has had a similar life-threatening episode. It is speculated that the infants' recurrent "salt-and-water-losing states" are secondary to either an anatomic or functional loss of the colon. This problem appears to be a poorly recognized sequela of bowel surgery and necrotizing enterocolitis, and early reanastomosis of discontinuous bowel should be of benefit.

Dehydration↗

Indomethacin tocolysis and risk of necrotizing enterocolitis.

OBJECTIVE: To investigate the possible association of indomethacin tocolysis with neonatal necrotizing enterocolitis. METHODS: A case-control study was performed for the period November 1, 1997, through May 1, 1999. All cases of proven necrotizing enterocolitis were ascertained, and four controls for each case were randomly identified from all Special Care Nursery admissions before 37 weeks' gestation without necrotizing enterocolitis during that same period. RESULTS: During the 18-month period there were 24 cases of necrotizing enterocolitis out of 10,200 deliveries. Infants with necrotizing enterocolitis were more preterm (29.7 +/- 3.9 compared with 32.7 +/- 6.0 weeks; P =.03) and had lower birth weights (1453 +/- 777 compared with 1820 +/- 678 g; P =.02) compared with controls (n = 96). Respiratory distress syndrome (RDS) and sepsis were both significantly associated with an increased risk of necrotizing enterocolitis: 16 of 24 cases compared with 40 of 96 controls had RDS (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.0, 8.3) and 14 of 24 cases compared with 11 of 96 controls were septic (OR 10.8, 3.4, 95% CI 34.2). Indomethacin as a single agent was not associated with necrotizing enterocolitis (OR 1.0, 95% CI 0.2, 4.8). Using a logistic regression model, necrotizing enterocolitis was strongly associated with sepsis (adjusted OR 8.5, 95% CI 2.2, 32.5). When sepsis was removed from the model, double-agent tocolytic therapy was significantly associated with necrotizing enterocolitis (adjusted OR 6.9, 95% CI 1.1, 43.6). CONCLUSION: Tocolysis with indomethacin as a single agent was not associated with necrotizing enterocolitis in this case-control study. Combination tocolytic therapy may be a marker for subclinical infection and not causally related to necrotizing enterocolitis.

Adult↗

Necrotizing enterocolitis: a practical guide to its prevention and management.

Neonatal necrotizing enterocolitis is the second most common cause of morbidity in premature infants and requires intensive care over an extended period. Despite advances in medical and surgical techniques, the mortality and long-term morbidity due to necrotizing enterocolitis remain very high. Recent advances have shifted the attention of researchers from the classic triad (ischemia, bacteria, and the introduction of a metabolic substrate into the intestine) of necrotizing enterocolitis, to gut maturation, feeding practices, and inflammation. The focus on inflammation includes proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-18, and platelet-activating factor. Research related to the etiology of necrotizing enterocolitis has moved quickly from clostridial toxin to bacterial and other infectious agents. More recently, the pattern of bacterial colonization has been given emphasis rather than the particular species or strain of bacteria or their virulence. Gram-negative bacteria that form part of the normal flora are now speculated as important factors in triggering the injury process in a setting where there is a severe paucity of bacterial species and possible lack of protective Gram-positive organisms. Although the incidence of necrotizing enterocolitis has increased because of the survival of low birthweight infants, clinicians are more vigilant in their detection of the early gastrointestinal symptoms of necrotizing enterocolitis; however, radiographic demonstration of pneumatosis intestinalis remains the hallmark of necrotizing enterocolitis. With prompt diagnosis, a large proportion of infants with necrotizing enterocolitis are now able to be managed medically with intravenous fluid and nutrition, nasogastric suction, antibacterials, and close monitoring of physiologic parameters. In the advanced cases that require surgery, clinicians tend to opt for either simple peritoneal drainage (for very small and sick infants) or laparotomy and resection of the affected part. Intestinal transplantation later in life is available as a viable option for those who undergo resection of large segments of the intestine. It is becoming more evident that treatment of this devastating disease is expensive and comes with the toll of significant long-term sequelae. This has resulted in renewed interest in designing alternative strategies to prevent this serious gastrointestinal disease. Simple trophic feeding and the use of L-glutamine and arginine are novel avenues that have been examined. The use of probiotics ('friendly' bacterial flora) has been introduced as a promising tool for establishing healthy bacterial flora in the newborn gut to block the injury process that may ultimately lead to necrotizing enterocolitis.

Enterocolitis, Necrotizing↗

Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common emergency of the gastrointestinal tract occurring in the neonatal period. There have been published reports which suggest that oral immunoglobulins IgA and IgG produce an immunoprotective effect in the gastrointestinal mucosa. This systematic review was undertaken to clarify the issue. OBJECTIVES: To assess whether oral immunoglobulin administered to preterm and low birth-weight neonates reduces the incidence of necrotizing enterocolitis without adverse effects. SEARCH STRATEGY: The databases MEDLINE, CINAHL, Embase and the Cochrane Controlled Trials Register were searched. The text words 'necrotising enterocolitis OR necrotizing enterocolitis' AND 'immunoglobulin' with constraints 'neonate OR infant' were used. Proceedings of the Perinatal Society of Australia and New Zealand were hand searched. The computer neonatal discussion site 'Nicu Net' was also used. Additionally, all references in the identified trials were checked and authors were contacted to request any additional published or unpublished data. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials where oral immunoglobulins were used as prophylaxis against necrotizing enterocolitis in preterm (<37 weeks gestation) and/or low birth-weight (<2500 gms) neonates. DATA COLLECTION AND ANALYSIS: The procedures of the Cochrane Neonatal Review Group (CNRG) were used. The two reviewers independently assessed the trials for their methodological quality and subsequent inclusion in the review. Relative risk (RR), risk difference (RD), and number needed to treat (NNT) were used in the analysis. MAIN RESULTS: Five studies on oral immunoglobulin for the prevention of necrotizing enterocolitis were identified of which three met the inclusion criteria. In this review of the three eligible trials (including a total of 2095 neonates) the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC [RR 0.84 (95% CI 0.57, 1.25), RD -0.01 (95% CI -0.03, 0.01)], suspected NEC [RR 0.69 (95% CI 0.42, 1.13), RD -0.01 (95% CI -0.03, 0.00)], need for surgery [RR 0.21 (95% CI 0.02, 1.75), RD -0.03 (95% CI -0.06, 0.00)] or death from NEC [RR 1.10 (95% CI 0.47, 2.59), RD 0.00 (95% CI -0.01, 0.01)]. REVIEWER'S CONCLUSIONS: Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomised controlled trials of oral IgA alone for the prevention of NEC.

Administration, Oral↗

Necrotizing enterocolitis increases the bone resorption in premature infants.

BACKGROUND: Necrotizing enterocolitis is a common neonatal gastrointestinal disease that affects approximately 10% of premature infants less than 1500 g. The average mortality is 20-40% and survivors may present with diarrhea or malabsorption, intestinal strictures and fistulas, feeding abnormalities and failure to thrive. It is not clear whether the higher incidence of this gastrointestinal disease in premature infants contributes to the risk of osteopenia of prematurity. AIM: To examine bone turnover state in premature infants who had a necrotizing enterocolitis attack during postnatal period. STUDY DESIGN AND SUBJECTS: We examine the bone turnover markers in infants with necrotizing enterocolitis and compare them with infants with sepsis. Forty-one premature infants participated in the study and were divided into three groups. In group I, there were 14 premature infants who developed necrotizing enterocolitis with negative blood culture during their hospitalization. In group II, there were 12 premature infants who developed sepsis during their hospitalization. Age-matched 15 premature infants who were given parenteral nutrition served as control group (group III). Blood samples and 6-h urine samples were obtained for bone turnover markers and calcium, phosphorous, creatinine and 25-hydroxy vitamin D between the day 20 and 25. Bone osteoblastic activity was assessed by measurement of serum osteocalcin. Bone resorption was assessed by measurement of serum levels of beta-CrossLaps and urinary deoxypyridinoline. RESULTS: There were no significant differences in bone osteoblastic activity among the groups, but bone resorption markers were significantly higher in infants with necrotizing enterocolitis compared to other groups (p < 0.016). CONCLUSION: Necrotizing enterocolitis increases the bone resorption in premature infants. It may be related with reduced glucagon like peptide-2 levels, a new intestinal hormone that is primary secreted from distal small intestine.

Amino Acids↗

An epidemiological study of neonatal necrotizing enterocolitis.

OBJECTIVE: To study epidemiology including various risk factors incorporated in neonatal necrotizing enterocolitis in Kashmir. METHODS: A retrospective hospital based study on 3235 neonates admitted in Neonatal Intensive Care Unit of Sheri-Kashmir Institute, were evaluated. Forty two were diagnosed as cases of Neonatal Necrotizing Enterocolitis on the basis of various clinical and radiological parameters and grouped in 3 stages as per modified Bell's classification. The case records of these 42 babies and 303 of the control group were reviewed for the purported risk factors and recorded on pretested proforma and finally statistically analyzed. RESULTS: Over a period of 10 years, we documented necrotizing enterocolitis in 42 neonates, with an incidence of 1% of all Neonatal Intensive Care Unit admissions and 1% of all live births. Eighty one percent were less than 2000 gms and 76% less than 36 weeks of gestation. Twenty four percent had stage I disease, 33% had stage II, and 43% babies had stage III disease. Multiple risk factors were present in these babies, with significant differences among Necrotizing Enterocolitis and the control group of patients, particularly hypothermia (P < 0.001), respiratory distress (P < 0.05), polycythemia (P < 0.001) acidosis (P < 0.01), sepsis (P < 0.001), enteral feeding and asphyxia (P < 0.001). Of the 59 babies (< 2000 gms) with hypothermia (< 35 degrees C), 39% developed Necrotizing Enterocolitis, compared to 4% babies (11/278), who did not have hypothermia, statistically a significant finding. Mean birth weight and gestational age were lower than in control group (P < 0.05). The age of presentation was 5.2 +/- 4.0 days and majority (81%) presented during first week of life, most severe cases presenting earlier than the mild cases. Severity of Necrotizing Enterocolitis as per modified Bell's classification and mortality was inversely related to birth weight and gestational age. One hundred percent mortality was noted in the babies, with birth weight less than 1000 gms and gestational age less than 28 weeks. The overall mortality was 45%, for stage I, 20%; for stage II, 36% and 67% for stage III. Necrotizing Enterocolitis cases accounted for maximum mortality in Neonatal Intensive Care Unit than in control group (P < 0.001). CONCLUSION: Recognition of factors such as prematurity, low birth weight, hypothermia, asphyxia and their timely prevention would help in reducing morbidity and mortality due to Necrotizing Enterocolitis.

Birth Weight↗

Necrotizing enterocolitis: diagnosis with CT examination of urine after enteral administration of iodinated water-soluble contrast material.

PURPOSE: To develop a new method for diagnosing necrotizing enterocolitis with use of computed tomography (CT). MATERIALS AND METHODS: Urine specimens from 22 neonates were obtained 8-12 hours after iohexol was administered enterally. Twelve neonates had suspected (n = 5) or definite (n = 7) necrotizing enterocolitis, and 10 neonates without necrotizing enterocolitis underwent routine upper gastrointestinal study. Urine from another 13 neonates without necrotizing enterocolitis who did not receive iohexol was collected. The attenuation coefficient of each urine specimen was determined with CT. RESULTS: The mean CT attenuation coefficient of urine from neonates who did not receive iohexol was 5.6 HU +/- 3.9, and that from neonates without necrotizing enterocolitis who underwent upper gastrointestinal study was 6.7 HU +/- 3.2. The mean CT attenuation coefficient of urine from patients with suspected necrotizing enterocolitis was 26.0 HU +/- 3.4, and that in patients with definite necrotizing enterocolitis was 71.0 HU +/- 18.8. The mean CT attenuation coefficients in neonates with necrotizing enterocolitis were significantly different from that in patients without necrotizing enterocolitis who underwent upper gastrointestinal study. CONCLUSION: Urine from neonates with necrotizing enterocolitis show significantly higher CT attenuation coefficients than those from patients without necrotizing enterocolitis. CT examination of urine may allow early detection of necrotizing enterocolitis.

Administration, Oral↗

Term neonates with hemolytic disease of the newborn and necrotizing enterocolitis: a report of two cases.

Necrotizing enterocolitis in term infants is uncommon, and when it occurs it is usually associated with risk factors such as asphyxia, congenital heart disease, or polycythemia. It has been reported in term neonates after exchange transfusion for hemolytic disease of the newborn; therefore exchange transfusion is recognized as a risk factor. We report two term neonates with hemolytic disease of the newborn resulting from anti-c rhesus incompatibility in whom necrotizing enterocolitis developed before exchange transfusions. These cases implicate hemolytic disease of the newborn without exchange transfusion as a risk factor for necrotizing enterocolitis in term infants.

Enterocolitis, Pseudomembranous↗

[Advances in necrotizing enterocolitis].

OBJECTIVE: To evaluate recently reported findings on necrotizing enterocolitis, Paying particular attention to pathogenesis, management and preventative strategies. DATA SOURCES: The articles covered in this report consist of randomized and quasi-randomized trials, case control studies, meta-analyses and reviews published recently. Certain other articles were also included because of their utmost importance to the subject. RESULTS: Necrotizing enterocolitis remains a major cause of morbidity and mortality in preterm infants. Those who are born with intra-uterine-growth retardation are at a several-fold increased risk. Possible pathophysiologic processes beginning in utero and continuing after birth are discussed in this review. Other factors involved in the process are related to the role of arginine and the production of intestinal nitric oxide and the action of epidermal growth factor in the regulation of cell regeneration. Perforated necrotizing enterocolitis is a complex surgical problem; definitive evidence-based guidelines for the best approach are yet to be determined. After surgery, although residual small bowel length and the presence of the ileo-cecal valve remain important predictors of duration of parenteral nutrition in infants, other factors, such as the early use of breast milk or amino acid-based formula, may also play a role in intestinal re-adaptation. Prevention strategies have centered on feeding practices and emerging experiments such as amino acid supplementation, are also discussed. CONCLUSION: Significant results in terms of mortality and morbidity will be achieved through better understanding of necrotizing enterocolitis pathogenesis and clinical and surgical management in addition to the employment of preventative strategies.

Enterocolitis, Necrotizing↗

Characterization of gut microbiota signatures in Indian preterm infants with necrotizing enterocolitis: a shotgun metagenomic approach.

INTRODUCTION: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease that primarily affects preterm infants. Predisposing risk factors for NEC include prematurity, formula feeding, anemia, and sepsis. To date, no studies have investigated the gut microbiota of preterm infants with NEC in India. METHOD: In the current study, shotgun metagenomic sequencing was performed on fecal samples from premature infants with NEC and healthy preterm infants (n = 24). Sequencing was conducted using the NovaSeq X Plus platform, generating 2 &#xd7; 150 bp paired-end reads. The infants were matched based on gestational age and postnatal age. RESULT: The median time to NEC diagnosis was 9 days (range: 1-30 days). Taxonomic analysis revealed a high prevalence of Enterobacteriaceae at the family level, with the genera Klebsiella and Escherichia particularly prominent in neonates with NEC. No statistically significant differences in alpha or beta diversity were observed between stool samples from infants with and without NEC. Linear regression analysis demonstrated that Enterobacteriaceae were significantly more abundant in stool samples from infants with NEC than without NEC (q < 0.05). Differential abundance analysis using Linear Discriminant Analysis Effect Size (LEfSe) identified Klebsiella pneumoniae and Escherichia coli as enriched in the gut microbiota of preterm infants with NEC. Functional analysis revealed an increase in genes associated with lipopolysaccharide (LPS) O-antigen, the type IV secretion system (T4SS), the L-rhamnose pathway, quorum sensing, and iron transporters, including ABC transporters, in stool samples from infants with NEC. CONCLUSION: The high prevalence of Enterobacteriaceae and enrichment of LPS O-antigen and T4SS genes may be associated with NEC in Indian preterm infants.

Humans↗

Neonatal necrotizing enterocolitis. A 10 year experience.

Neonatal necrotizing enterocolitis was seen in 42 of 5,030 infants (0.83 percent) admitted to our neonatal intensive care units. The condition developed more than 1 week after birth in most infants. This group included most of the very low birth weight infants. Forty-one of the 42 infants had enteral feedings before the onset of enterocolitis, which developed within 72 hours from the start of feedings in 19 infants (45 percent). Twenty-nine patients (69 percent) underwent surgery. Mortality in this group was 38 percent overall and 28 percent in the infants considered salvageable at laparotomy. The interval from diagnosis to surgery was 24 hours or less in 65 percent of cases, emphasizing the fulminant nature of the disease in many patients. Three of the 14 patients who died underwent no surgery. Pneumoperitoneum was one of the initial radiologic signs in 10 patients (24 percent). The necrotizing enterocolitis observed was similar clinically to that reported by others. The strikingly low incidence of enterocolitis in the neonatal intensive care units in Oregon (0.83 percent) contrasts with the generally reported incidence of 3 to 8 percent in other neonatal intensive care units. We attribute the low incidence of necrotizing enterocolitis in our experience to delay of enteral feedings and reliance on prolonged peripheral or central total parenteral nutrition, or both, for nutritional maintenance of stressed or low birth weight infants.

Birth Weight↗

Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids.

Necrotizing enterocolitis is the most frequently occurring gastrointestinal disorder in premature neonates. Animal models of necrotizing enterocolitis and prenatal administration of cortisone have demonstrated that cortisone may accelerate maturation of the mucosal barrier, therefore reducing the incidence of this gastrointestinal disorder. The authors present a review of the literature of the most important risk factors associated with necrotizing enterocolitis, such as inflammatory gastrointestinal mediators, enteral feeding and bacterial colonization, and immaturity of the gastrointestinal barrier, and we emphasize the necessity for additional studies to explore the prenatal administration of cortisone as a preventive strategy for necrotizing enterocolitis.

Animals↗

[Necrotizing enterocolitis (NEC) in the newborn].

Necrotizing enterocolitis (NEC) is a disease of the premature neonate that requires early therapy, sometimes even surgery and therefore early diagnosis. In general, plain radiography of the abdomen and sonography are valuable imaging techniques for diagnosis of NEC. COURSE OF NEC: The disease starts with distension of small bowel loops. Furthermore the children develop pneumatosis in the bowel wall, which is a nonspecific pattern. If the NEC persists, the air passes into the portal vein system, causing a pneumoportogram. Finally, the disease can lead to perforation. In doubtful cases, the plain radiogram must be repeated within a period of 6 h. With sonography distension of the bowel, thickening of and pneumatosis in the bowel wall, the pneumoportogram and free intraperitoneal fluid can be easily depicted. The most common complications of NEC are intestinal stenosis and strictures that can lead to ileus. DIFFERENTIAL DIAGNOSIS: Focal perforation of ileum, volvulus and Hirschsprung's disease are some of the differential diagnoses.

Diagnosis, Differential↗

T-cell-mediated mucosal immunity is attenuated in experimental necrotizing enterocolitis.

In premature infants with necrotizing enterocolitis (NEC) the gastrointestinal mucosal barrier is immature, but little is known about the immune response of immature bowel. The aim of this study was to evaluate the intestinal mucosal immune response in experimental NEC. In general anaesthesia, NEC was induced in six newborn piglets by injection of bovine casein into terminal ileum. Six controls received an equal amount of saline. Four hours later, samples were taken from the macroscopically most affected part of the treated loop and from the macroscopically healthy untreated intestine. Monoclonal antibodies to porcine CD1, CD2, CD4, CD8, CD45 and IgM were used for immunohistochemical staining. Casein-treated bowel showed typical macro- and microscopic findings of NEC. No changes were found in the saline-treated bowel. In both groups the bowel outside the treatment sector was normal. In casein-treated animals, treated samples showed significant decrease in density of CD4+ cells when compared with saline-treated controls. Similar trend was found in CD2+ and CD8+ cells but without statistical significance. Macroscopically healthy proximal untreated samples showed significant decrease in densities of CD2+, CD4+ and CD8+ lymphocytes in casein-treated group when compared with control samples. In casein-treated animals the density of CD45+ cells in the non-injected bowel was also decreased, but this did not reach statistical significance. Densities of CD1+ and IgM+ cells did not differ between casein-treated and saline-treated groups. A significant T-cell decrease was found in the present NEC model. Surprisingly, this was most prominent in the macroscopically healthy bowel outside the casein injection segment. The reason for T-cell decrease remains unclear, but bovine casein is known to contain peptide fractions that can modulate immune function. These findings may have implications in the design of neonatal milk formulas.

Animals↗