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Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants
Pak Cheung Ng, … , Yuk Ming Dennis Lo, Terence Chuen Wai Poon
Pak Cheung Ng, … , Yuk Ming Dennis Lo, Terence Chuen Wai Poon
Published July 1, 2010
Citation Information: J Clin Invest. 2010;120(8):2989-3000. https://doi.org/10.1172/JCI40196.
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Technical Advance Infectious disease

Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants

Abstract

Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.

Authors

Pak Cheung Ng, Irene Ling Ang, Rossa Wai Kwun Chiu, Karen Li, Hugh Simon Lam, Raymond Pui On Wong, Kit Man Chui, Hon Ming Cheung, Eddy Wing Yin Ng, Tai Fai Fok, Joseph Jao Yiu Sung, Yuk Ming Dennis Lo, Terence Chuen Wai Poon

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Need for biomarkers to differentiate between NEC and sepsis

Submitter: Kostan Reisinger | k.reisinger@maastrichtuniversity.nl

Authors: Joep P.M. Derikx, and Boris W. Kramer

Departments of Surgery and Paediatrics, Maastricht University Medical Center +, Maastricht, The Netherlands

Published October 27, 2010

With great interest we read the article by Ng et al. (1). Their thorough and profound approach, led to the discovery of two promising biomarkers for the detection of both sepsis and necrotizing enterocolitis in preterm infants, serum amyloid A (SAA) and proapolipoprotein CII (pro-apoC2). As the authors state on page 2997, medical management of NEC and sepsis is identical in the initial stage. However, the decision to perform surgery in case of suspected NEC remains critical (2), while the needless use of antibiotics in non-sepsis cases seems less dangerous. When resection of affected bowel is not achieved timely, the subsequent disease progression can be devastating with high mortality (3). It is therefore highly desirable to distinguish between sepsis and NEC at an early time-point. Recent literature indicates markers of gut injury to be suitable candidates for this purpose (4, 5). Moreover, Thuijls et al. reported promising results on gut-specific non-invasive markers, namely urinary intestinal Fatty Acid Binding Protein (iFABP) and fecal calprotectin, to differentiate between NEC and sepsis (6). Combining these markers with the reported inflammatory markers of Ng et al. might overcome the essential diagnostic dilemma of early discrimination of NEC and sepsis in preterm neonates.

References

  1. Ng PC, Ang IL, Chiu RW, Li K, Lam HS, Wong RP, Chui KM, Cheung HM, Ng EW, Fok TF, Sung JJ, Lo YM, Poon TC. Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants. J Clin Invest 2010;120:2989-3000.
  2. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet 2006;368:1271-83.
  3. O'Neill JA, Jr., Stahlman MT, Meng HC. Necrotizing enterocolitis in the newborn: operative indications. Ann Surg 1975;182:274-9.
  4. Derikx JP, Evennett NJ, Degraeuwe PL, Mulder TL, van Bijnen AA, van Heurn LW, Buurman WA, Heineman E. Urine based detection of intestinal mucosal cell damage in neonates with suspected necrotising enterocolitis. Gut 2007;56:1473-5.
  5. Guthmann F, Borchers T, Wolfrum C, Wustrack T, Bartholomaus S, Spener F. Plasma concentration of intestinal- and liver-FABP in neonates suffering from necrotizing enterocolitis and in healthy preterm neonates. Mol Cell Biochem 2002;239:227-34.
  6. Thuijls G, Derikx JP, van Wijck K, Zimmermann LJ, Degraeuwe PL, Mulder TL, Van der Zee DC, Brouwers HA, Verhoeven BH, van Heurn LW, Kramer BW, Buurman WA, Heineman E. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg 2010;251:1174-80.

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