Fecal Calprotectin Concentrations in Premature Infants Have a Lower Limit and Show Postnatal and Gestational Age Dependence

HELIOS Children's Hospital Wuppertal, Witten/Herdecke University, Wuppertal, Germany.
Neonatology (Impact Factor: 2.65). 05/2012; 102(1):68-74. DOI: 10.1159/000337841
Source: PubMed


There is a need for reliable diagnostic biomarkers in necrotizing enterocolitis (NEC). Whereas fecal calprotectin (fCP) has been reported to have insufficient sensitivity and specificity, no previous study has stratified for gestational and postnatal age.
We aimed to provide developmental specific fCP data in premature infants and to analyze its value in detecting intestinal distress and episodes of NEC.
Between April 2008 and December 2009, 1,899 fecal samples were obtained from 206 very low birth weight infants.
Mean gestational age (GA) was 28.5 weeks and birth weight 1,057 g. 19 (9.2%) patients developed NEC stage II+, of whom 5 had fulminant NEC with unusually low fCP concentrations in meconium and afterwards. fCP levels showed significant gestational and postnatal age dependent dynamics with particularly low levels in extremely premature infants. In infants with a GA <26 + 1 weeks using GA-adapted reference values, the sensitivity for discriminating moderate NEC from healthy infants and infants with intestinal distress was 0.89 for a cut-off of 180 and 210 µg/g, respectively, at onset of symptoms. Specificity was 0.96 and 0.84. Fulminant NEC was characterized by unusually low fCP concentrations with a cut-off of <24 µg/g having a sensitivity of 0.84 and a specificity of 0.72 for identifying those cases.
fCP levels depend on gestational and postnatal age and in contrast to adults, there is a lower limit in premature infants. Taking these observations into account when defining reference values and interpreting fCP data in the clinical context, fCP can be a useful marker in identifying premature infants with gastrointestinal distress and NEC in particular.

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Available from: Andreas C W Jenke, Mar 22, 2015
    • "In the study of Zoppelli et al.,[19] mean GA was 28.5 weeks and birth weight 1,057 g. Zoppelli et al.,[19] declared that diagnosis of NEC is made on the basis of clinical criteria since there are no specific diagnostic tests but our study showed a significant increase in WBC and neutrophils counts and a highly significant decrease in hemoglobin and platelet counts in patient group. Two of our patients (14%) had suspect NEC (bell's stage I), 8 (53%) had definite NEC (bell's stage IIa or IIb), 5 (33%) had advanced NEC (bell's stage IIIa or IIIb). "
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    ABSTRACT: Calprotectin is a 36 kDa protein present in the cytoplasm of the neutrophil has antimicrobial and apoptosis inducing activities. In vitro studies have shown that calprotectin inhibits the growth of various microorganisms. Necrotizing enterocolitis (NEC) remains one of the leading causes of morbidity and mortality in neonatal intensive care units (NICU), affecting up to 5% of premature infants. Fecal calprotectin is resistant to degradation and has been proposed as a useful marker of gastrointestinal inflammation. The objective of the present study is to evaluate fecal calprotectin concentrations in NEC. Fifteen neonates with a clinical diagnosis of NEC were studied; they admitted at NICU of Zagazig University Hospital. In addition, 20 age sex matched neonates fed all caloric requirement served as the control group. All neonates were subjected to history taking, clinical examination, laboratory investigations (complete blood count, C-reactive protein) and determination of stool calprotectin. There was a highly significant increase in fecal calprotectin in patients than control and there was a highly significant increase in its fecal level in died patients than living one. Also significant increase in fecal calprotectin level with increasing severity of NEC. Fecal calprotectin measurements could be a valuable tool for the investigation of preterm and full term infants suspected of having NEC.
    No preview · Article · Mar 2014
    • "However, others found that calprotectin could actually serve as a biomarker if corrected for gestational age. Sensitivity and specificity for distinguishing moderate NEC from healthy infants and those with intestinal distress was fairly high with this correction.[90] "
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    ABSTRACT: Necrotizing enterocolitis (NEC) remains a very devastating problem within the very low birth weight neonatal population. Several experimental therapies are being tested in animal models and soon may be ready for human trials. Despite this progress, we currently have no way to identify infants who would be optimal targets for therapy. Specifically, we are unable to predict which infants will progress to the more severe Bell's stage of disease that may necessitate surgery. Ideally, an algorithm could be constructed that would encompass multiple neonatal and maternal risk factors as well as potential biologic markers of disease so that these infants could be identified in a more timely fashion. This review summarizes the known risk factors and biomarkers of disease in hopes of stimulating clinical research to identify such an "early warning" NEC algorithm.
    No preview · Article · Mar 2014
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    • "Given the extremely high mortality of NEC-totalis, it is critical to be able to identify this subset of NEC patients as early as possible. Unfortunately, few clinical or biochemical parameters exist that can reliably identify patients with NEC-totalis, or which can reliably predict which patients with NEC will develop this severe form of the disease [11] [12] [13] [14]. Despite this subset of infants representing the most severely affected patients, it is somewhat surprising that there is no effective scoring system available to identify these patients, and thus to potentially guide therapy. "
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    ABSTRACT: Background/Purpose Necrotizing enterocolitis totalis (NEC-totalis) is the severest form of NEC, with mortality rate of almost 100% even in the busiest neonatal centers. Despite such a prognosis, its risk factors remain elusive. We seek to identify clinical and laboratory parameters that differentiate NEC-totalis from NEC, and to use these factors to develop a scoring system to identify patients at risk for NEC-totalis upon presentation. Method NEC patients were identified from our electrical medical record using ICD9 code. Diagnosis of NEC-totalis was based on operative and autopsy reports. Patients were divided into 2 groups: NEC-but-no-totalis and NEC-totalis. Clinical/laboratory data were obtained for each group. T-test, multivariate logistic regression and backward stepwise regression analysis were performed to identify risk factors for NEC-totalis and these risk factors were formulated into a “Totalis Score.” Result Among 157 NEC patients, 13 had NEC-totalis. NEC-totalis patients, compared to NEC alone, had fewer platelets, older age at diagnosis of NEC and greater phosphorus and creatinine levels. A 0-5 point scale “Totalis Score” based on these risk factors had sensitivity of 92% and a specificity of 78% for the diagnosis of NEC-totalis. Conclusion Low platelet, high phosphorus, high creatinine and older age at diagnosis of NEC were associated with a greater risk of developing NEC-totalis.
    Full-text · Article · Jan 2013 · Journal of Pediatric Surgery
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