Necrotizing Enterocolitis-Associated Acute Kidney Injury-Transforming the Paradigm.

Necrotizing enterocolitis (NEC) is one of the most common conditions requiring emergency surgery in the neonatal intensive care unit and is associated with a septic shock-like state contributing to multiorgan dysfunction. NEC affects 6 to 10% of very low-birth-weight infants and remains a leading cause of death. The occurrence of severe acute kidney injury (AKI) following surgical NEC is a harbinger of multiple morbidities. This review presents current evidence about the clinical impact of NEC-associated AKI on the clinical outcomes. Studies evaluating nephroprotective strategies to prevent AKI and its consequences are greatly needed to improve the postoperative recovery and clinical outcomes in neonates with NEC. Future observational studies and clinical trials in preterm infants with NEC prioritize measuring short-term (AKI) and longer term (chronic kidney disease) kidney outcomes. KEY POINTS: · Severe AKI is common following surgical NEC.. · Severe AKI following NEC is associated with poor clinical outcomes.. · Studies evaluating nephroprotective strategies to prevent AKI and its consequences are needed.. IMPACT: · Severe AKI (stage 2 and 3) occurs in 32.6% of neonates after NEC diagnosis and in 58.7% following surgical NEC diagnosis.. · NEC-associated AKI is associated with severe postoperative course, moderate-to-severe bronchopulmonary dysplasia, surgical complications, brain injury, and longer hospital stay in preterm infants.. · Severity of NEC-associated AKI can be utilized by bedside providers for the prognostication of clinical outcomes in preterm infants..

Clinical and Growth Correlates of Retinopathy of Prematurity in Preterm Infants with Surgical Necrotizing Enterocolitis and Intestinal Perforation.

OBJECTIVE: This study aimed to identify the clinical and growth parameters associated with retinopathy of prematurity (ROP) in infants with necrotizing enterocolitis (NEC) and spontaneous ileal perforation (SIP). STUDY DESIGN: We conducted a retrospective cohort study that compared clinical data before and after NEC/SIP onset in neonates, categorizing by any ROP and severe ROP (type 1/2) status. RESULTS: The analysis included 109 infants with surgical NEC/SIP. Sixty infants (60/109, 55%) were diagnosed with any ROP, 32/109 (29.3%) infants (22% type 1 and 7.3% type 2) with severe ROP. On univariate analysis, those with severe ROP (32/109, 39.5%) were of lower median gestational age (GA, 23.8 weeks [23.4, 24.6] vs. 27.3 [26.3, 29.0], p < 0.001), lower median birth weight (625 g [512, 710] vs. 935 [700, 1,180], p < 0.001) and experienced higher exposure to clinical chorioamnionitis (22.6 vs. 2.13%, p < 0.006), and later median onset of ROP diagnosis (63.0 days [47.0, 77.2] vs. 29.0 [19.0, 41.0], p < 0.001), received Penrose drain placement more commonly (19 [59.4%] vs. 16 [34.0%], p = 0.04), retained less residual small bowel (70.0 cm [63.1, 90.8] vs. 90.8 [72.0, 101], p = 0.007) following surgery, were exposed to higher FiO2 7 days after birth (p = 0.001), received ventilation longer and exposed to higher FiO2 at 2 weeks (p < 0.05) following NEC and developed acute kidney injury (AKI) more often (25 [86.2%] vs. 20 [46.5%], p = 0.002) than those without ROP. Those with severe ROP had lower length, weight for length, and head circumference z scores. In an adjusted Firth's logistic regression, GA (adjusted odds ratio [aOR] = 0.51, 95% confidence interval [CI]: [0.35, 0.76]) and diagnosis at later age (aOR = 1.08, 95% CI: [1.03, 1.13]) was shown to be significantly associated with any ROP. CONCLUSION: Infants who develop severe ROP following surgical NEC/SIP are likely to be younger, smaller, have been exposed to more O2, develop AKI, and grow poorly compared with those did not develop severe ROP. KEY POINTS: · Thirty percent of infants with NEC/SIP had severe ROP.. · Those with severe ROP had poor growth parameters before and after NEC/SIP.. · Risk factors based ROP prevention strategies are needed to have improved ophthalmic outcomes..

Is Necrotizing Enterocolitis and Spontaneous Intestinal Perforation Part of Same Disease Spectrum - New Insights?

The diagnosis of NEC is based on the presence of pneumatosis, dilated bowel loops, portal venous gas, or pneumoperitoneum on the abdominal x-ray. Published studies suggest that the appearance of pneumatosis most likely depends on the gestational age, with a shift occurring between 27-28 weeks. For infants of gestational age under 27 weeks, pneumoperitoneum is the most likely presentation of bowel injury due to the thin bowel wall and the colonization of the gut with the non-gas-producing bacteria. Assessment of postoperative morbidity and white matter injury on the brain MRI at term equivalent age in a cohort of preterm infants failed to identify differences between SIP and NEC groups when confirmed by histology. These findings illustrate the difficulty in conclusively identifying cases as SIP or NEC, particularly when gestational age is considered and raise speculation that both conditions lie on the same spectrum of intestinal injury.

Clinical Correlates of Cholestasis in Preterm Infants with Surgical Necrotizing Enterocolitis.

Background: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC). Methods: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not. Results: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%; p = 0.002), had higher mean C-reactive protein levels 2 weeks after NEC diagnosis (p = 0.009), had blood culture-positive sepsis [25 (40.3%) vs 4 (13.8%); p = 0.011], received parenteral nutrition (PN) for longer durations (108.4 ± 56.63 days vs 97.56 ± 56.05 days; p = 0.007), had higher weight-for-length z scores at 36 weeks' postmenstrual age [-1.0 (-1.73, -0.12) vs -1.32 (-1.76, -0.76); p = 0.025], had a longer length of hospital stay (153.7 ± 77.57 days vs 112.51 ± 85.22 days; p = 0.024), had intestinal failure more often (61% vs 25.0%, p = 0.003), had more surgical complications (50% vs 27.6%; p = 0.044), and had >1 complication (21% vs 3.4%; p = 0.031). Using linear regression, the number of days after surgery when feeds could be started [OR 15.4; confidence interval (CI) 3.71, 27.13; p = 0.009] and the postoperative ileus duration (OR 11.9, CI 1.1, 22.8; p = 0.03) were independently associated with direct bilirubin between 2 and 5 mg/dL (mild-moderate cholestasis) at 2 months of age. The duration of PN was independently associated with direct bilirubin >5 mg/dL (severe cholestasis) at 2 months of age in these patients. Conclusion: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer periods. Our data suggest that identification and prevention of risk factors such as sepsis and surgical complications and early feeds following NEC surgery may improve outcomes.

Necrotizing Enterocolitis (NEC): A Devastating Disease of Prematurity.

Necrotizing Enterocolitis (NEC) is a common and devastating gastrointestinal emergency that primarily affects premature infants. The incidence of necrotizing enterocolitis is 6-10% among infants with birth weight less than 1500 grams. The mortality due to NEC has not improved significantly despite advances in neonatal care and better understanding of clinical and basic sciences. The pathogenesis of NEC is not well understood and several factors such as prematurity, abnormal colonization with pathogenic bacteria, feeding practices, blood transfusion and altered intestinal barrier function may be involved. The clinical presentation of NEC could be sudden and the treatment plan could vary with the stage and type of presentation. Further research is needed to better understand the pathophysiology of NEC and, biomarkers for prediction, prevention and treatment need to be developed. Further clinical trials are needed to determine prevention and treatment modalities for this devastating disease.