Diagnostic efficacy of high-frequency ultrasound and X-ray contrast enema in colonic strictures after necrotizing enterocolitis: a retrospective study.

OBJECTIVE: To compare the efficacy of high-frequency ultrasound and X-ray contrast enema in the diagnosis of colonic strictures after necrotizing enterocolitis. METHODS: This study included pediatric patients who developed progressive abdominal distension or constipation after conservative treatment for necrotizing enterocolitis at our hospital between June 2012 and April 2020. All patients had high-frequency ultrasounds and X-ray contrast enema, and we used surgery, pathology, and telephone return visits as the reference standard. Patients with colonic strictures were confirmed by surgery and pathology. A patient was considered without colonic stricture if no stricture was reported or did not have related symptoms during telephone return visits. The areas under the Receiver operating characteristic (ROC) curves were used as evaluation indexes to compare the differential efficacy of high-frequency ultrasound and X-ray contrast enema. RESULTS: A total of 81 patients have been included in this study. Among them, 49 patients were diagnosed with colonic strictures after necrotizing enterocolitis. The AUCs for high-frequency ultrasound and X-ray contrast enema were 0.990 vs 0.938, respectively (p > 0.05). CONCLUSION: The diagnostic efficacy of high-frequency ultrasound was similar to that of X-ray contrast enema, furthermore this study also demonstrates the benefits of using high-frequency ultrasound to identify colonic strictures after necrotizing enterocolitis.

Clinical features and management of post-necrotizing enterocolitis strictures in infants: A multicentre retrospective study.

To explore the clinical features and management of post-necrotizing enterocolitis strictures.Clinical data from 158 patients with post-necrotizing enterocolitis strictures were summarized retrospectively in 4 academic pediatric surgical centers between April 2014 and January 2019. All patients were treated conservatively in the internal medicine department. All patients underwent preoperative X-ray examinations, 146 patients underwent gastrointestinal contrast studies, and 138 patients underwent rectal mucosal biopsies. All of the patients were treated surgically.Of the 158 patients, 40 of them had necrotizing enterocolitis (NEC) Bell stage Ib, 104 had Bell stage IIa, and 14 had Bell stage IIb. In these patients, the clinical signs of intestinal strictures occurred at mean of 47.8 days after NEC. In 158 patients, 146 underwent barium enema examination, 116 demonstrated intestinal strictures, and 10 demonstrated microcolon and poor development. A total of 138 patients underwent rectal mucosal biopsies, and 5 patients had Hirschsprung disease. Intraoperative exploration showed that intestinal post-NEC strictures occurred in the ileal (17.7%, 28/158) and colon (82.3%, 130/158), including ascending colon, transverse colon and descending colon, and multiple strictures were detected in 36.1% (57/158) patients. Surgical resection of stricture segments in the intestine and primary end-to-end anastomosis were performed in 142 patients, and the remaining 16 patients underwent staged surgeries. In the 146 patients with complete follow-up data, 9 had postoperative adhesions: 4 of them received conservative treatment, and the others underwent a second operation. Fifteen patients were hospitalized 1 to 3 times for malnutrition and dehydration due to repeated diarrhea; these patients eventually recovered and were discharged smoothly. All the other patients had uneventful recoveries without stricture recurrence.Post-NEC strictures mostly occurred in the colon, and there were some cases of multiple strictures. A gastrointestinal contrast study was the preferred method of examination. Preoperative rectal mucosal biopsy resulted in a diagnosis of Hirschsprung disease, and then a reasonable treatment protocol was chosen. Surgical resection of stricture segments in the intestine and primary end-to-end anastomosis achieved good therapeutic effects with favorable prognoses in these patients.

The value of contrast studies in the evaluation of bowel strictures after necrotising enterocolitis.

PURPOSE: Strictures of the bowel are a frequent complication post-necrotising enterocolitis (NEC). Contrast studies are routinely performed prior to stoma closure following NEC. The aim of this study was to evaluate the ability of these studies to detect strictures and also directly compare them to operative and histological findings. METHODS: Two hundred and fourteen neonates who had a diagnosis of NEC (Bell stage 2 or greater) in a single unit (2007-2011) were analysed. Their case notes, radiology, and histology were reviewed. RESULTS: One hundred and sixteen neonates underwent an emergency laparotomy and 77 had stomas fashioned. Sixty-six patients had a contrast study prior to stoma closure (distal loopogram 18, contrast enema 37, both studies 11). Colonic strictures were reported in 18 patients and small bowel strictures were reported in two patients. Fourteen of these colonic strictures were confirmed at operation and on histology but three colonic strictures were missed on contrast studies; one patient had had both contrast studies and the other two only a distal loopogram. Two small bowel strictures reported were confirmed and an additional small bowel stricture missed on distal loopogram was also detected at the time of operation. The incidence of post-op strictures was 19 out of 68 patients (27.9 %) and 16 (84.2 %) of these strictures were found in the colon. Contrast enemas had a much higher sensitivity for detecting post-NEC colonic strictures than distal loopograms; 93 versus 50 %, respectively; however, they are more likely to give a false positive result and therefore their specificity is lower; 88 versus 95 %, respectively. CONCLUSION: Colon is the commonest site for post-NEC stricture and contrast enema is the study of choice for detecting these strictures prior to stoma closure.

Nutrition in the Cardiac Newborns: Evidence-based Nutrition Guidelines for Cardiac Newborns.

Both protein and energy malnutrition are common in neonates and infants with congenital heart disease (CHD). Neonates with CHD are at increased risk of developing necrotizing enterocolitis (NEC), particularly the preterm population. Mortality in patients with CHD and NEC is higher than for either disease process alone. Standardized feeding protocols may affect both incidence of NEC and growth failure in infants with CHD. The roles of human milk and probiotics have not yet been explored in this patient population.

Comparison of brainstem auditory evoked response at different click rates between preterm babies after neonatal necrotizing enterocolitis and healthy preterm babies.

BACKGROUND: Neonatal necrotizing enterocolitis (NEC) is associated with an increased incidence of poor neurodevelopment. The knowledge of underlying neurophysiology is very limited, and the influence of NEC on the preterm brainstem is very poorly understood. OBJECTIVE: To assess the effect of NEC on the immature auditory brainstem by excluding any possible confounding effect of preterm birth. METHODS: We recorded and analyzed brainstem auditory evoked response (BAER) at different click rates in preterm babies (30-34 weeks gestation) after NEC. The results were compared with those in age-matched healthy preterm babies who had no NEC. RESULTS: At click rate 21/s, the latencies of BAER waves I and III in the preterm NEC babies were similar to those babies without NEC. However, wave V latency was longer in the NEC babies than in those without NEC. The I-V interpeak interval was also longer in the NEC babies than in those without NEC. These abnormalities were persistent at higher click rates 51 and 91/s. Wave I amplitude in the preterm NEC babies did not differ significantly from that in those without NEC, but wave III and V amplitudes were smaller than in those without NEC at all 21-91/s clicks. CONCLUSIONS: Compared with healthy preterm babies, preterm babies after NEC showed a major increase in wave V latency and I-V interval at all 21-91/s clicks. Brainstem auditory function is impaired in preterm NEC babies after excluding the possible confounding effect of preterm birth. Neonatal NEC and associated perinatal conditions adversely affect the premature brainstem.

Utility of gastrointestinal fluoroscopic studies in detecting stricture after neonatal necrotizing enterocolitis.

OBJECTIVES: We report our institution's 5-year experience with upper gastrointestinal study with small bowel follow-through (UGI-SBFT) and contrast enema (CE) for the diagnosis of a post-necrotizing enterocolitis (NEC) stricture. We hypothesized that sensitivity and specificity of UGI-SBFT and CE were <85% in diagnosing a post-NEC stricture. METHODS: A retrospective observational cohort study was performed. Included patients were neonates diagnosed as having Bell's modified stage 2 or 3 NEC who had undergone UGI-SBFT and/or CE to evaluate for a stricture. Exploratory laparotomy was used to definitively determine the stricture presence, which was confirmed by pathology. An infant was categorized as having no stricture if no surgical intervention occurred or if no stricture was reported on pathology following surgical resection. RESULTS: A total of 56 patients met inclusion criteria, with 51 UGI-SBFT and 85 CE performed. A total of 25 patients were diagnosed as having a stricture. For small bowel (SB) strictures, CE compared with UGI-SBFT has a higher sensitivity (0.667 vs 0.00) and a similar specificity (0.857 vs 0.833). For SB and/or colonic strictures, CE has a sensitivity of 0.667 and a specificity of 0.951. Strictures were more likely to be found on imaging in symptomatic infants compared with those in asymptomatic infants (28% vs 8%, P = 0.002). CONCLUSIONS: CE should be the initial study in the diagnostic workup for a post-NEC stricture because this test has a higher likelihood of detecting a stricture if it is present. As a result of low sensitivity of UGI-SBFT and/or CE in the diagnosis of a post-NEC stricture, a negative study should not rule out the diagnosis of a stricture in persistently symptomatic patients.

Human milk fortifier: an occult cause of bowel obstruction in extremely premature neonates.

BACKGROUND: Human milk fortifier (HMF) is used in neonatal units throughout North America to facilitate growth of preterm infants. Little data is available on the gastrointestinal side effects and potential adverse events. The purpose of this paper was to present a series of infants presenting with bowel obstruction associated with HMF. METHODS: Cases of HMF obstruction were collected between January 2010 and December 2012. Charts were reviewed and relevant data was collected. RESULTS: During the study period, 7 premature infants presented with bowel obstruction secondary to intestinal concretions of HMF. All babies were premature with gestational ages from 25 to 27 weeks. Birth weight was less than 1000 grams in all patients. Patients presented with feeding intolerance, bilious aspirates, abdominal distension, and obstipation. Four of the patients presented with acute deterioration and required urgent surgical intervention. CONCLUSIONS: HMF is an important source of nutritional support in infants, which is felt to be safe. We present a series of infants where its use has resulted in significant complications. HMF should be used with caution in infants, especially those with a history of necrotizing enterocolitis. Further research should examine the calcium, protein, and fatty acid concentration tolerable in the gastrointestinal tract of infants.

Evidence-based management of neonatal vomiting in the emergency department.

Vomiting accounts for up to 36% of neonatal visits to the emergency department. The causes of vomiting can range from benign to life-threatening. Evidence to guide the diagnosis and management of neonatal vomiting in the emergency department is limited. History and physical examination are extremely important in these cases, especially in identifying red flags such as bilious or projectile emesis. A thorough review is presented, discussing various imaging modalities, including plain abdominal radiography, upper gastrointestinal studies, ultrasonography, and contrast enema. A systematic approach in the emergency department, as outlined in this review, is required to identify the serious causes of vomiting in the neonate.

Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country.

BACKGROUND: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements. OBJECTIVE: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth. DESIGN: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth. RESULTS: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478). CONCLUSION: Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.

Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model.

BACKGROUND: Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. MATERIALS AND METHODS: Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1ß, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. RESULTS: Levels of cytokines IL-1ß, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. CONCLUSIONS: Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade.

Prevention and reversal of intestinal failure-associated liver disease in premature infants with short bowel syndrome using intravenous fish oil in combination with omega-6/9 lipid emulsions.

Although premature infants with short bowel syndrome are at the highest risk of developing intestinal failure-associated liver disease (IFALD), they have great capacity for intestinal growth and adaptation if IFALD can be prevented. Conventional soybean oil-based intravenous lipid emulsions have been associated with IFALD. This study presents data on 5 premature neonates with short bowel syndrome treated with a combination of parenteral fish oil- and olive/soybean-based lipid emulsion for periods ranging between 7 and 17 months. Despite an enteral tolerance of less than 50% in 4 of these patients during their first year of life, direct bilirubin levels normalized while on this combination of ClinOleic (Baxter, Maurepas, France)/Omegaven (Fresenius Kabi, Bad Homburg, Germany) at a 1:1 ratio. None of our patients developed irreversible IFALD even though all of them were premature, had undergone multiple major surgical procedures, and had experienced several episodes of sepsis. Thus far, we have not seen any adverse effects of this mixed lipid emulsion in these preterm infants. All 5 patients are growing and developing well and have normal liver function.

Risk factors for parenteral nutrition­associated liver disease following surgical therapy for necrotizing enterocolitis: A Glaser Pediatric Research Network Study [corrected].

OBJECTIVE: The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children. PATIENTS AND METHODS: : From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥ 2 mg/dL or ALT ≥ 2 × the upper limit of normal in the absence of sepsis after ≥ 14 days of exposure to PN. RESULTS: Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97-12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56-3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5-4.7; P = 0.001) times greater in patients with ≥ 4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD. CONCLUSIONS: The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.

Symptomatic acquired zinc deficiency in at-risk premature infants: high dose preventive supplementation is necessary.

Zinc is a cofactor for several enzymes involved in many metabolisms. Zinc deficiency induces various disorders such as acrodermatitis enteropathica, either inherited or acquired. We report three cases of premature infants (24-31 wks gestational age) with low birthweight (650 to 940 g) and enteropathy, two of whom presented with necrotizing enterocolitis. All infants were fed by total parenteral nutrition. At a chronological age ranging from 73 to 80 days, all infants developed a periorificial dermatitis. Before the onset of the first signs, they had received zinc supplementation ranging from 146% to 195% of the recommended dose (400 microg/kg/day). Increased zinc supplementation over a course of 6-18 days induced a complete resolution of symptoms in all cases. No abnormality in the neurologic examination and no recurrence were observed at the end of the zinc treatment. Low birthweight premature infants with enteropathy on total parenteral nutrition are at risk of developing zinc deficiency. The usual recommended zinc supplementation is probably insufficient for those infants. A delay in the diagnosis of zinc deficiency may lead to severe complications.

Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis.

AIM: This study aimed to compare the long-term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight < or = 1250 gm) who received supplementation with L-arginine during the first 28 days of life with controls. METHODS: Surviving infants enrolled in a randomised control study of L-arginine supplementation were prospectively followed longitudinally to determine their neurodevelopmental outcomes at 36 months of adjusted age. Neurologic examination and neurodevelopmental assessments were performed by examiners who were unaware of the original treatment assignments. RESULTS: A total of 132 children (95% of survivors) were evaluated at 36 months adjusted age. In the group given L-arginine, 5 of 61 (8.1%) had major neurodevelopmental disabilities, defined as the presence of one or more of cerebral palsy, cognitive delay (cognitive index <70), bilateral blindness or bilateral hearing loss requiring hearing aids as compared with 9 of 71 (12.6%) in the placebo group (relative risk, 0.64; 95 % confidence interval, 0.22-1.82; P= 0.40). CONCLUSIONS: There is no increase in neurodevelopmental disability in preterm infants who received L-arginine supplementation.

[Intestinal fistula: an unusual complication of necrotizing enterocolitis in the preterm infant]. / La fistule digestive : une complication inhabituelle de l'entérocolite ulcéronécrosante du nouveau-né prématuré

Intestinal fistula is a rare complication in necrotizing enterocolitis (NEC) and is typically associated with a colonic stricture. We report the case of a preterm infant with severe NEC, who developed an ileocolic fistula followed by the appearance of a colonic stricture after surgical treatment. This report shows how complex the outcome of NEC can be: a contrast enema should be done in NEC when the clinical or biological outcome is not favorable, in order not to delay the diagnosis of intestinal fistula.

Estenosis intestinal secundaria a enterocolitis necrotizante / Intestinal stenosis following necrotizing enterocolitis

En forma secundaria a la Enterocolitis Necrotizante (ECN) podemos observar una estenosis cicatricial del segmento intestinal comprometido; situación que ha sido observada tanto en pacientes con tratamiento médico o quirúrgico de la enfermedad. Se analiza la historia clínica de 9 pacientes que requirieron reparación quirúrgica de esta patología. En tres de ellos por cuadro agudo de obstrucción intestinal y en el resto como hallazgo de laparotomía para reconstrucción del tránsito o en examen contrastado de colon. La estenosis comprometió exclusivamente al intestino grueso, con un predominio en el colon transverso y descendente, con una longitud variable, asociado a la presencia de múltiples adenopatías. Se realizó resección del segmento estrecho con anastomosis primaria termino-terminal en todos ellos. El estudio anátomo-patológico mostró tejido de granulación, fibrosis esclerótica de la pared y diversos grados de estrechez fibrosa de tipo cicatricial. Solo 1 paciente presentó una dehiscencia de sutura intestinal, con peritonitis secundaria, que requirió exploración y reanastomosis. No hubo mortalidad. En conclusión, es aconsejable realizar estudio contrastado de rutina a todos los pacientes que han sufrido este trastorno. Resolver los casos de estenosis secundaria con resección y anastomosis primaria del segmento comprometido.

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.