Routine contrast enema prior to stoma reversal seems only required following treatment for necrotizing enterocolitis: An evaluation of the diagnostic accuracy of the contrast enema.

INTRODUCTION: Contrast enemas are often made prior to stoma reversal in order to detect distal intestinal strictures distal of the stoma. If untreated these strictures can cause obstruction which might necessitate redo-surgery. However, the value of contrast enemas is unclear. Therefore, we aim to evaluate the contrast enema's diagnostic accuracy in detecting strictures in children with a stoma. METHODS: Young children (≤3 years) treated with a stoma between 1998 and 2018 were retrospectively included. The STARD criteria were followed. Patients treated for anorectal malformations and those that died before stoma reversal were excluded. Surgical identification of strictures during reversal or redo-surgery within three months was used as gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) reflected diagnostic accuracy. RESULTS: In 224 included children, strictures were found during reversal in 10% of which 95% in patients treated for necrotizing enterocolitis. Contrast enema was performed in 68% of all patients and detected 92% of the strictures. In the overall cohort, the sensitivity was 100%, specificity 98%, PPV 88% and NPV 100% whilst the AUC was 0.98. In patients treated for NEC, the sensitivity was 100%, specificity 97%, PPV 88% and NPV 100% whilst the AUC was 0.98. CONCLUSION: Strictures prior to stoma reversal seem to be mainly identified in patients treated for NEC and not in other diseases necessitating a stoma. Moreover, the contrast enema shows excellent diagnostic accuracy in detecting these strictures. For this reason we advise to only perform contrast enemas in patients treated for NEC. LEVEL OF EVIDENCE: II.

Body Composition following Necrotising Enterocolitis in Preterm Infants.

BACKGROUND: The optimal nutritional regimen for preterm infants, including those that develop necrotising enterocolitis (NEC), is unknown. OBJECTIVE: The objective here was to evaluate body composition at term in infants following NEC, in comparison with healthy infants. The primary outcome measure was non-adipose tissue mass (non-ATM). METHODS: We compared body composition assessed by magnetic resonance imaging at term in infants born <31 weeks of gestational age that participated in NEON, a trial comparing incremental versus immediate delivery of parenteral amino acids on non-ATM, and SMOF versus intralipid on intrahepatocellular lipid content. There were no differences in the primary outcomes. We compared infants that received surgery for NEC (NEC-surgical), infants with medically managed NEC (NEC-medical), and infants without NEC (reference). RESULTS: A total of 133 infants were included (8 NEC-surgical; 15 NEC-medical; 110 reference). In comparison with the reference group, infants in the NEC-surgical and NEC-medical groups were significantly lighter [adjusted mean difference (95% CI) NEC-surgical: -630 g (-1,010, -210), p = 0.003; NEC-medical: -440 g (-760, -110), p = 0.009] and the total adipose tissue volume (ATV) was significantly lower [NEC-surgical: -360 cm3 (-516, -204), p < 0.001; NEC-medical: -127 cm3 (-251, -4); p = 0.043]. There were no significant differences in non-ATM [adjusted mean difference (95% CI) NEC-surgical: -46 g (-281, 189), p = 0.70; NEC-medical: -122 g (-308, 63), p = 0.20]. CONCLUSION: The lower weight at term in preterm infants following surgically and medically managed NEC, in comparison to preterm infants that did not develop the disease, was secondary to a reduction in ATV. This suggests that the nutritional regimen received was adequate to preserve non-ATM but not to support the normal third-trimester deposition of adipose tissue in preterm infants.

Small intestinal intraepithelial TCRγδ+ T lymphocytes are present in the premature intestine but selectively reduced in surgical necrotizing enterocolitis.

BACKGROUND: Gastrointestinal barrier immaturity predisposes preterm infants to necrotizing enterocolitis (NEC). Intraepithelial lymphocytes (IEL) bearing the unconventional T cell receptor (TCR) γδ (γδ IEL) maintain intestinal integrity and prevent bacterial translocation in part through production of interleukin (IL) 17. OBJECTIVE: We sought to study the development of γδ IEL in the ileum of human infants and examine their role in NEC pathogenesis. We defined the ontogeny of γδ IEL proportions in murine and human intestine and subjected tcrδ-/- mice to experimental gut injury. In addition, we used polychromatic flow cytometry to calculate percentages of viable IEL (defined as CD3+ CD8+ CD103+ lymphocytes) and the fraction of γδ IEL in surgically resected tissue from infants with NEC and gestational age matched non-NEC surgical controls. RESULTS: In human preterm infants, the proportion of IEL was reduced by 66% in 11 NEC ileum resections compared to 30 non-NEC controls (p<0.001). While γδ IEL dominated over conventional αß IEL early in gestation in mice and in humans, γδ IEL were preferential decreased in the ileum of surgical NEC patients compared to non-NEC controls (50% reduction, p<0.05). Loss of IEL in human NEC was associated with downregulation of the Th17 transcription factor retinoic acid-related orphan nuclear hormone receptor C (RORC, p<0.001). TCRδ-deficient mice showed increased severity of experimental gut injury (p<0.05) with higher TNFα expression but downregulation of IL17A. CONCLUSION: Complimentary mouse and human data suggest a role of γδ IEL in IL17 production and intestinal barrier production early in life. Specific loss of the γδ IEL fraction may contribute to NEC pathogenesis. Nutritional or pharmacological interventions to support γδ IEL maintenance in the developing small intestine could serve as novel strategies for NEC prevention.

Frequency of symptomatic zinc deficiency in very low birth weight infants.

Current concepts on zinc requirements for premature infants rely on studies dating back more than 20 years. Given that nowadays more premature infants frequently survive we aimed to obtain recent frequency data on zinc deficiency in very low birth weight (VLBW) infants.226 VLBW infants born between July 2005 and December 2009 were retrospectively included in this study. Mean gestational age (GA) was 28.7 weeks (range 23+0 to 38+0) and mean birth weight 1120g (range 354-1495). All infants received zinc supplementation according to the ESPGHAN guidelines. 26 (11.5%) patients showed clinical signs for zinc deficiency of whom 15 had serum zinc concentrations < 50µg/dl, 9 between 50 and 70 µg/dl and 2 > 70 µg/dl. Infants presenting with dermatitis had significantly lower concentrations (mean 26.7 µg/dl, range 19-31) when compared to infants with diarrhoea or isolated peripheral oedema (35.3 µg/dl and 51.8 µg/dl respectively). Strongest independent risk factors were low GA, being small for GA and suffering from intestinal resection due to necrotizing enterocolitis. Frequency of zinc concentrations <50 µg/dl were calculated to be 6.6% in VLBW infants.Even though current guidelines for zinc supplementation were followed the frequency of zinc deficiency was found to be unexpectedly high in ELBW and SGA infants. Despite the retrospective nature of this single centre study, our data strongly suggest that recommendations on zinc supplementation in ELBW and SGA infants should be reviewed.

Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants.

Copper deficiency can cause bone lesions in infants, which might be confused with child abuse. Two extremely low birth weight preterm infants had complicated medical courses requiring prolonged parenteral nutrition for short-gut syndrome, which led to the development of cholestasis. Both had spent their entire lives in the hospital. They had been on prolonged ventilator support for chronic lung disease. They developed signs of copper deficiency between 5 and 6 months of age, initially raising child abuse concerns. Musculoskeletal discomfort led to the recognition of radiographic findings of metabolic bone disease. Included were osteoporosis, metaphyseal changes, and physeal disruptions. Copper levels were low; both low copper parenteral nutrition and gut losses from refeeding diarrhea likely contributed to their deficiency. Therapeutic supplementation with copper corrected their deficits and clinical and radiologic findings. The information from these cases, in particular, their radiologic findings, indicate the need to monitor copper status in at-risk premature infants. These findings may aid prevention and earlier recognition of copper deficiency. Their specific radiologic and clinical findings should aid differentiation of such children from abused infants.

Intestinal failure-associated liver disease in surgical infants requiring long-term parenteral nutrition.

PURPOSE: Our aim was to determine incidence, severity, and outcome, as well as predisposing factors and underlying diagnoses, of intestinal failure-associated liver disease (IFALD) in surgical infants requiring long-term parenteral nutrition (PN). METHODS: We retrospectively studied surgical infants receiving PN for at least 28 days for congenital or acquired intestinal anomalies over a 5-year period (January 2006 to December 2010). Intestinal failure-associated liver disease was defined as type 1 (early)--persistent elevation of alkaline phosphatase for 6 weeks or longer; type 2 (established)--additional elevated total bilirubin (≥ 50 µmol/L); and type 3 (late)--additional clinical signs of end-stage liver disease. RESULTS: Eighty-seven infants required PN for at least 28 days. Intestinal failure-associated liver disease occurred in 29 infants (33%). Intestinal failure-associated liver disease was managed medically in all but 2 patients who underwent intestinal elongation. None were referred for intestinal or liver transplant. Intestinal failure-associated liver disease has been reversed in 17 (59%) of cases to date. Sixty-one children receiving long-term PN (70%) have achieved enteral autonomy, whereas 12 (14%) require home PN. Severity of IFALD was significantly associated with duration of PN and female sex. CONCLUSION: Intestinal failure-associated liver disease remains a fairly common but rarely life-threatening complication of intestinal failure in surgical infants. Intestinal failure-associated liver disease can be reversed in more than half of these children, and enteral autonomy was achieved in more than two thirds, even with minimal use of intestinal elongation. This is the first study to demonstrate an association between the severity of IFALD in surgical infants and female sex.

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.

Pancytopenia with myelodysplasia due to copper deficiency.

We present a case of pancytopenia in a 9-month-old infant with total parenteral nutrition (TPN) dependence due to short bowel syndrome. Bone marrow examination revealed left-shifted myeloid maturation, erythroid and myeloid dysplasia with normal iron stores. Serum copper level was 2 microm/dl (normal range 90-190 mcg/dl). After supplementation, copper levels normalized at 143 mcg/dl, and the macrocytic anemia, neutropenia, and thrombocytopenia resolved. Copper deficiency should be considered in the differential diagnosis of cytopenias and myelodsyplasia, particularly in the growing number of pediatric patients with TPN dependency or malabsorption.