European Journal of Pediatrics

, Volume 172, Issue 4, pp 501–508

Clinical signs to identify late-onset sepsis in preterm infants

  • Jolita Bekhof
  • Johannes B. Reitsma
  • Joke H. Kok
  • Irma H. L. M. Van Straaten
Original Article

DOI: 10.1007/s00431-012-1910-6

Cite this article as:
Bekhof, J., Reitsma, J.B., Kok, J.H. et al. Eur J Pediatr (2013) 172: 501. doi:10.1007/s00431-012-1910-6


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.


Premature infant Infection Nosocomial sepsis Signs and symptoms Diagnosis 



Late-onset sepsis


Neonatal intensive care unit


Central venous catheter


Area under the curve of the receiver operating characteristic curve


Odds ratio


Confidence interval

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jolita Bekhof
    • 1
  • Johannes B. Reitsma
    • 2
  • Joke H. Kok
    • 3
  • Irma H. L. M. Van Straaten
    • 1
  1. 1.Princess Amalia Department of PediatricsIsala KliniekenZwolleThe Netherlands
  2. 2.Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Department of NeonatologyAcademic Medical CenterAmsterdamThe Netherlands

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