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The β-glucosidase assay: a new diagnostic tool for necrotizing enterocolitis. Sensitivity, specificity, and predictive values

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Abstract

We aimed to establish the utility of serum cytosolic β-glycosidase (CBG) assay as a NEC diagnosis tool. CBG activity has been compared in 192 NEC-free (NEC−) and 13 NEC-affected (NEC+) neonates, with modified Bell’s stages II/III, born at Reina Sofia University Hospital; additional blood hematology, microbiology, and biochemical parameters have been assayed. NEC+ neonates have higher serum CBG activity, 26.4 ± 12.4 mU/mg; 95 % CI (18.8–33.9), than NEC− infants, 11.0 ± 6.6 mU/mg; 95 % CI (10.1–11.9) (p < 0.0001). The CBG cutoff value in the ROC curve, 15.6 mU/mg, discriminates NEC+/NEC− infants with 84.6 % sensitivity, 85.9 % specificity, 37.9 positive predictive value and 98.2 negative predictive value, 6.11 positive likelihood ratio and 0.18 negative likelihood ratio, 33.61 DOR, and 0.89 AUC. A combined panel [CBG + aspartate aminotransferase + C-reactive protein] shows a 0.90 AUC value in multiple linear regressions.

Conclusions: The serum CBG level is a good NEC diagnosis test and a novel NEC biomarker which may become a screening tool.

What is known:

•NEC affects ∼2.5 % of infants at NICU, ∼90 % of them weighing <1500 g.

•NEC requires a careful differential diagnosis, being lethal if not diagnosed and treated.

What is new:

•CBG assay will be useful to determine infants without NEC and preventing unnecessary treatment.

•CBG assay could discriminate NEC better than other gut-specific sera protein biomarkers.

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Notes

  1. Gómez-Chaparro Moreno JL, et al. (2005, Oct). Determinación de los niveles de la enzima β-glucosidasa citosólica en sangre. Poster presented at the XIX “Congreso Nacional de la Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria”. Madrid.

Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUC:

Area under curve

BUN:

Blood urea nitrogen

CBG:

Cytosolic β-glycosidase

DOR:

Diagnostic odds ratio

ICC:

Intraclass correlation coefficient

LH+ :

Positive likelihood ratio

LH− :

Negative likelihood ratio

MLR:

Multiple logistic regression

NEC:

Necrotizing enterocolitis

NEC+ :

NEC-affected neonates

NEC− :

Neonates without NEC

NPV:

Negative predictive value

NICU:

Neonatology intensive care unit

CRP:

C-reactive protein

PPV:

Positive predictive value

PRBT:

Packed red blood transfusion

ROC:

Receiver operating characteristic

RSUH:

Reina Sofia University Hospital

S:

Sensitivity

SLR:

Simple logistic regression

SP:

Specificity

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Authors’ contributions

Dr. Gómez-Chaparro Moreno: conceptualized and designed the study; carried out the analyses, analyzed the data, and interpreted the results; reviewed and revised the manuscript. Dr. Rodríguez Torronteras: designed the study, supervised the data collection, and interpreted the results; reviewed and revised the manuscript. Dra. Ruiz Gónzalez: designed the study and carried out the analyses and analyzed the data. Dra. Izquierdo Palomares: conceptualized and designed the study; carried out the analyses and helped in collecting the data; revised the manuscript. Dra. Ruiz Laguna: carried out the analyses and analyzed the data. Dr. Bonilla Valverde: carried out the analyses, analyzed the data, and interpreted the results. Prof. López-Barea: conceptualized and designed the study; supervised the data collection and interpreted the results; drafted the article and revised critically the manuscript. Prof. Delgado Rubio: revised critically the manuscript. All authors approved the final manuscript as submitted.

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Authors and Affiliations

  1. Experimental Unit. Córdoba Health District. Andalusian Health Service, C/ Isla de Lanzarote s/n Edificio 2, 1ª Planta, 14011, Córdoba, Spain

    José Luis Gómez-Chaparro Moreno

  2. Department of Epidemiology. Córdoba Health District, Andalusian Health Service, C/ Isla de Lanzarote s/n Edificio 2, 1ª Planta, Córdoba, 14011, Spain

    Alejandro Rodríguez Torronteras

  3. Neonatology Unit, Pediatrics Service, RSUH. Andalusian Health Service, Avda. Menendez Pidal s/n., Córdoba, 14004, Spain

    María Dolores Ruiz González

  4. Pediatrics Radiology Section, Radiodiagnostic Service, RSUH, Andalusian Health Service, Avda. Menendez Pidal s/n., Córdoba, 14004, Spain

    Lucía Izquierdo Palomares

  5. Department of Biochemistry and Molecular Biology of Córdoba University, Severo Ochoa Building. A4 Highway, Km 396a, Rabanales Campus, Córdoba, 14071, Spain

    Daniel Bonilla Valverde, Julia Ruiz Laguna & Juan López-Barea

  6. Department of Pediatric of San Pablo-CEU University, School of Medicine. Monteprincipe Campus. Alcorcón, Madrid, 28925, Spain

    Alfonso Delgado Rubio

Authors
  1. José Luis Gómez-Chaparro Moreno
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  2. Alejandro Rodríguez Torronteras
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Corresponding author

Correspondence to José Luis Gómez-Chaparro Moreno.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Funding source

This study was funded by grants from (1) the Health Research Fund, Carlos III Institute of Health, Health and Consumption Ministry, Spain (FIS, 05/609) and (2) the Health Agency, Andalusian Government, Spain (146/05).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional RSUH research committee and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all neonates’ parents or legal tutor included in the study.

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Communicated by Patrick Van Reempts

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Gómez-Chaparro Moreno, J.L., Rodríguez Torronteras, A., Ruiz González, M.D. et al. The β-glucosidase assay: a new diagnostic tool for necrotizing enterocolitis. Sensitivity, specificity, and predictive values. Eur J Pediatr 175, 931–941 (2016). https://doi.org/10.1007/s00431-016-2724-8

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  • DOI: https://doi.org/10.1007/s00431-016-2724-8

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