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Clinical signs to identify late-onset sepsis in preterm infants

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Abstract

Late-onset neonatal sepsis (LOS) in preterm infants is an important cause of morbidity and mortality in preterm infants. Since presenting symptoms may be non-specific and subtle, early and correct diagnosis is challenging. We aimed to develop a nomogram based on clinical signs, to assess the likelihood of LOS in preterms with suspected infection without the use of laboratory investigations. We performed a prospective cohort study in 142 preterm infants <34 weeks admitted to the neonatal intensive care unit with suspected infection. During 187 episodes, 21 clinical signs were assessed. LOS was defined as blood culture-proven and/or clinical sepsis, occurring after 3 days of age. Logistic regression was used to develop a nomogram to estimate the probability of LOS being present in individual patients. LOS was found in 48 % of 187 suspected episodes. Clinical signs associated with LOS were: increased respiratory support (odds ratio (OR) 3.6; 95 % confidence interval (CI) 1.9–7.1), capillary refill (OR 2.2; 95 %CI 1.1–4.5), grey skin (OR 2.7; 95 %CI 1.4–5.5) and central venous catheter (OR 4.6; 95 %CI 2.2–10.0) (area under the curve of the receiver operating characteristic curve 0.828; 95 %CI 0.764–0.892). Conclusion: Increased respiratory support, capillary refill, grey skin and central venous catheter are the most important clinical signs suggestive of LOS in preterms. Clinical signs that are too non-specific to be useful in excluding or diagnosing LOS were temperature instability, apnoea, tachycardia, dyspnoea, hyper- and hypothermia, feeding difficulties and irritability.

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Abbreviations

LOS:

Late-onset sepsis

NICU:

Neonatal intensive care unit

CVC:

Central venous catheter

AUC:

Area under the curve of the receiver operating characteristic curve

OR:

Odds ratio

CI:

Confidence interval

References

  1. Bayak MA (2004) What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med 66:411–421

    Article  Google Scholar 

  2. Berger A, Salzer HR, Weninger M, Sageder B, Aspöck C (1998) Septicaemia in an Austrian neonatal intensive care unit: a 7-year analysis. Acta Paediatrica 87:1066–1069

    Article  PubMed  CAS  Google Scholar 

  3. Brodie SB, Sands KE, Gray JE, Parker RA, Goldmann A, Davis RB, Richardson DK (2000) Occurrence of nosocomial bloodstream infections in six neonatal intensive care units. Pediatr Infect Dis J 19:56–65

    Article  PubMed  CAS  Google Scholar 

  4. Conroy ME, Shi HN, Walker WA (2009) The long-term health effects of neonatal microbial flora. Curr Opin Allergy Clin Immunol 9:197–201

    Article  PubMed  Google Scholar 

  5. Fanaroff AA, Korones SB, Wright LL, Verter J, Poland RL, Bauer CR, Tyson JE, Philips JB 3rd, Edwards W, Lucey JF, Catz CS, Shankaran S, Oh W (1998) Incidence, presenting features, risk factors and significance of late onset septicaemia in very low birth weight infants. Pediatr Infect Dis J 17:593–598

    Article  PubMed  CAS  Google Scholar 

  6. Fischer JE (2005) Physicians' ability to diagnose sepsis in newborns and critically ill children. Pediatr Crit Care Med 6:S120–S125

    Article  PubMed  Google Scholar 

  7. Franz AR, Bauer K, Schalk A, Garland SM, Bowman ED, Rex K, Nyholm C, Norman M, Bougatef A, Kron M, Mihatsch WA, Pohlandt F, International IL-8 Study Group (2004) Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multi-centre, randomized, controlled trial. Pediatrics 114:1–8

    Article  PubMed  Google Scholar 

  8. Gerdes JS (1991) Clinicopathologic approach to the diagnosis of neonatal sepsis. Clin Perinatol 18:361–381

    PubMed  CAS  Google Scholar 

  9. Kudawla M, Dutta S, Narang A (2008) Validation of a clinical score for the diagnosis of late onset neonatal septicemia in babies weighing 1000–2500 g. J Trop Pediatr 54:66–69

    Article  PubMed  Google Scholar 

  10. Mahieu LM, De Muynck AO, De Dooy JJ, Laroche SM, Van Acker KJ (2000) Prediction of nosocomial sepsis in neonates by means of a computer-weighted bedside scoring system (NOSEP). Crit Care Med 28:2026–2033

    Article  PubMed  CAS  Google Scholar 

  11. Modi N, Doré CJ, Saraswatula A, Richards M, Bamford KB, Coello R, Holmes A (2009) A case definition for national and international neonatal bloodstream infection surveillance. Arch Dis Child fetal Neonatal Ed 94:F8–F12

    Article  PubMed  CAS  Google Scholar 

  12. Neu J (2007) Perinatal and neonatal manipulation of the intestinal microbiome: a note of caution. Nutr Rev 65:282–285

    Article  PubMed  Google Scholar 

  13. Ohlin A (2011) What is neonatal sepsis? Acta Paediatr 100:7–8

    Article  PubMed  Google Scholar 

  14. Ohlin A, Björkqvist M, Montgomery SM, Schollin J (2010) Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis. Acta Paediatr 99:1635–1640

    Article  PubMed  Google Scholar 

  15. Okascharoen C, Hui C, Cairnie J, Morris AM, Kirpalani H (2007) External validation of bedside prediction score for diagnosis of late-onset neonatal sepsis. J Perinatol 27:496–501

    Article  PubMed  CAS  Google Scholar 

  16. Okascharoen C, Sirinavin S, Thakkinstian A, Kitayaporn D, Supapanachart S (2005) A bedside prediction-scoring model for late-onset neonatal sepsis. J Perinatol 25:778–783

    Article  PubMed  Google Scholar 

  17. Reitsma JB, Rutjes AW, Khan KS, Coomarasamy A, Bossuyt PM (2009) A review of solutions for diagnostic accuracy studies with an imperfect or missing reference standard. J Clin Epidemiol 62:797–806

    Article  PubMed  Google Scholar 

  18. Singh S, Dutta S, Narang A (2003) Predictive clinical scores for diagnosis of late onset neonatal septicemia. J Trop Pediatr 49:235–239

    Article  PubMed  Google Scholar 

  19. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Waldemar AC, Ehrenkranz RA, Lemons LA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile L-A, Poole WK (2002) Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatri 110:285–291

    Article  Google Scholar 

  20. Tibby SM, Hatherill M, Murdoch IA (1998) Capillary refill and core-peripheral temperature gap as indicators of haemodynamic status in paediatric intensive care patients. Arch Dis Child 80:163–166

    Article  Google Scholar 

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Acknowledgments

We wish to thank L.J.M. Groot-Jebbink and C.M. Bunkers, research nurses, for their vital assistance in collecting and managing the data.

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Authors and Affiliations

  1. Princess Amalia Department of Pediatrics, Isala Klinieken, Dr van Heesweg 2, PO Box 10400, 8000 GK, Zwolle, The Netherlands

    Jolita Bekhof & Irma H. L. M. Van Straaten

  2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    Johannes B. Reitsma

  3. Department of Neonatology, Academic Medical Center, Amsterdam, The Netherlands

    Joke H. Kok

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  1. Jolita Bekhof
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  2. Johannes B. Reitsma
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  3. Joke H. Kok
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  4. Irma H. L. M. Van Straaten
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Correspondence to Jolita Bekhof.

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Bekhof, J., Reitsma, J.B., Kok, J.H. et al. Clinical signs to identify late-onset sepsis in preterm infants. Eur J Pediatr 172, 501–508 (2013). https://doi.org/10.1007/s00431-012-1910-6

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  • DOI: https://doi.org/10.1007/s00431-012-1910-6

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