Non-invasive serum amyloid A (SAA) measurement and plasma platelets for accurate prediction of surgical intervention in severe necrotizing enterocolitis (NEC).

OBJECTIVE: To evaluate the value of biomarkers to detect severe NEC. SUMMARY BACKGROUND DATA: The time point of surgery in necrotizing enterocolitis (NEC) is critical. Therefore, there is a need for markers that detect severe NEC, because clinical signs of severe NEC often develop late. This study evaluated the value of biomarkers reflecting intestinal cell damage and inflammation to detect severe NEC. METHODS: 29 neonates with NEC were included. Two definitions of moderate versus severe NEC were analyzed: medical NEC (n = 12) versus surgical or fatal NEC (n = 17); and Bell stage II NEC (n = 13) versus stage III NEC (n = 16). Urinary intestinal fatty acid binding protein (I-FABP), serum amyloid A (SAA), C3a and C5a, and fecal calprotectin were measured. C-reactive protein (CRP), white blood cell count (WBC) and platelet count data were measured in blood. RESULTS: In both definitions of moderate versus severe NEC, urinary SAA levels were significantly higher in severe NEC. A cut-off value of 34.4 ng/ml was found in surgical NEC versus medical NEC (sensitivity, 83%; specificity, 83%; LR+, 4.88 (95% CI, 1.37-17.0); LR-, 0.20 (95% CI, 0.07-0.60)) at diagnosis of NEC and at one day prior to surgery in neonates who were operated later on. Combination of urinary SAA and platelet count increased the accuracy, with a sensitivity, 94%; specificity, 83%; LR+, 5.53 (95% CI, 1.57-20.0); and LR-, 0.07 (95% CI, 0.01-0.48). CONCLUSION: Urinary SAA is an accurate marker in differentiating severe NEC from moderate NEC; particularly if combined with serum platelet count.

Noninvasive measurement of intestinal epithelial damage at time of refeeding can predict clinical outcome after necrotizing enterocolitis.

BACKGROUND: Reintroduction of enteral nutrition in neonates with necrotizing enterocolitis (NEC) should take place when the gut is ready for its normal function. Too early a start of oral feeding might lead to disease relapse, whereas prolonged discontinuation of enteral nutrition is associated with impaired gut function and parenteral nutrition-related complications. This study evaluated whether noninvasive urinary measurement of intestinal fatty acid binding protein (I-FABP) at the time of refeeding can predict clinical outcome in neonates with NEC. METHODS: Urinary I-FABP concentrations were measured in 21 infants with NEC just before reintroducing enteral nutrition. Poor outcome was defined as unsuccessful reintroduction of enteral feeding (EF), (re)operation for NEC, or death related to NEC after reintroduction of EF. RESULTS: Median urinary I-FABP levels in neonates with poor outcome (n = 5) were significantly higher as compared with I-FABP levels in neonates with good outcome (n = 16) (P < 0.01). A clinically significant cutoff value of 963 pg/ml was found to discriminate between infants with poor outcome and those with good outcome (sensitivity 80%, specificity 94%). CONCLUSION: Noninvasive urinary I-FABP measurement at time of refeeding differentiates neonates with poor outcome from neonates with good outcome in NEC. Urinary I-FABP measurement may therefore be helpful in the timing of EF in neonates with NEC.

Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis.

BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, such as serum amyloid A (SAA) and fecal calprotectin. PURPOSE: The aim of the present study was to evaluate which combination of noninvasive measurement of inflammatory markers and I-FABP improves the diagnostic accuracy in neonates suspected for NEC. METHODS: In 62 neonates with clinical suspicion of NEC (29 with final diagnosis of NEC), urinary I-FABP, urinary SAA, and fecal calprotectin levels were determined quantitatively. Diagnostic accuracy was calculated for the combinations I-FABP-SAA and I-FABP-fecal calprotectin, using a multivariable logistic regression model. RESULTS: The combination of SAA and I-FABP did not increase the diagnostic accuracy of I-FABP. However, the combination of fecal calprotectin and I-FABP improved accuracy significantly. The combination of urinary I-FABP and fecal calprotectin measurement produced a sensitivity of 94%, a specificity of 79%, a positive likelihood ratio of 4.48, and a negative likelihood ratio of 0.08. CONCLUSION: The combination of noninvasive measurement of I-FABP and fecal calprotectin seems promising for diagnosing NEC at an early time point. Prospective analysis is required to confirm this finding and to evaluate better treatment strategies based on noninvasive measurement of I-FABP and calprotectin.

Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis.

OBJECTIVES: To improve diagnosis of necrotizing enterocolitis (NEC) by noninvasive markers representing gut wall integrity loss (I-FABP and claudin-3) and gut wall inflammation (calprotectin). Furthermore, the usefulness of I-FABP to predict NEC severity and to screen for NEC was evaluated. METHODS: Urinary I-FABP and claudin-3 concentrations and fecal calprotectin concentrations were measured in 35 consecutive neonates suspected of NEC at the moment of NEC suspicion. To investigate I-FABP as screening tool for NEC, daily urinary levels were determined in 6 neonates who developed NEC out of 226 neonates included before clinical suspicion of NEC. RESULTS: Of 35 neonates suspected of NEC, 14 developed NEC. Median I-FABP, claudin-3, and calprotectin levels were significantly higher in neonates with NEC than in neonates with other diagnoses. Cutoff values for I-FABP (2.20 pg/nmol creatinine), claudin-3 (800.8 INT), and calprotectin (286.2 microg/g feces) showed clinically relevant positive likelihood ratios (LRs) of 9.30, 3.74, 12.29, and negative LRs of 0.08, 0.36, 0.15, respectively. At suspicion of NEC, median urinary I-FABP levels of neonates with intestinal necrosis necessitating surgery or causing death were significantly higher than urinary I-FABP levels in conservatively treated neonates. Of the 226 neonates included before clinical suspicion of NEC, 6 developed NEC. In 4 of these 6 neonates I-FABP levels were not above the cutoff level to diagnose NEC before clinical suspicion. CONCLUSIONS: Urinary I-FABP levels are not suitable as screening tool for NEC before clinical suspicion. However, urinary I-FABP and claudin-3 and fecal calprotectin are promising diagnostic markers for NEC. Furthermore, urinary I-FABP might also be used to predict disease severity.