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Risk for Late-onset Blood-culture Proven Sepsis in Very-low-birth Weight Infants Born Small for Gestational Age: A Large Multicenter Study from the German Neonatal Network

Tröger, Birte MD*; Göpel, Wolfgang MD*; Faust, Kirstin MD*; Müller, Thilo*; Jorch, Gerhard MD; Felderhoff-Müser, Ursula MD, PhD; Gortner, Ludwig MD§; Heitmann, Friedhelm MD; Hoehn, Thomas MD, PhD; Kribs, Angela MD**; Laux, Reinhard MD††; Roll, Claudia MD, PhD‡‡; Emeis, Michael MD§§; Mögel, Michael MD¶¶; Siegel, Jens MD‖‖; Vochem, Matthias MD***; von der Wense, Axel MD†††; Wieg, Christian MD‡‡‡; Herting, Egbert MD, PhD*; Härtel, Christoph MD*for the German Neonatal Network

The Pediatric Infectious Disease Journal: March 2014 - Volume 33 - Issue 3 - p 238–243
doi: 10.1097/INF.0000000000000031
Original Studies

Background: It was the aim of this study to assess whether very-low-birth-weight (VLBW) infants born small for gestational age (SGA; birth weight less than 10th percentile) are at increased risk for late-onset sepsis.

Methods: This was a prospective, multicenter study of the German Neonatal Network including VLBW infants from 23 to < 32 weeks post menstrual age born 2009–2011. Outcomes were compared between VLBW infants born SGA (birth weight less than tenth percentile according to gestational age and gender) and non-SGA infants. The main outcome measure was at least 1 episode of late-onset sepsis defined as blood-culture–confirmed clinical sepsis occurring at ≥72 hours of age.

Results: 5886 VLBW infants were included. In SGA infants (n = 692), an increased incidence of late-onset sepsis was noted compared with non-SGA infants (20.1% vs. 14.3 %, P < 0.001). This difference was only observed among infants with a gestational age of 27 to < 32 weeks and attributed to sepsis episodes with coagulase-negative staphylococci (12.8% vs. 8.3%, P < 0.001). Different treatment modalities (eg more frequent use of central venous lines) and longer duration of invasive therapies (parenteral nutrition, mechanical ventilation, hospitalization) may account for the increased sepsis risk with coagulase-negative staphylococci in our SGA cohort. In a multivariate logistic regression analysis, higher gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.72–0.78, P< 0.0001], treatment with antenatal steroids (OR: 0.7, 95% CI: 0.53–0.92, P = 0.01), German descendance (OR: 0.76, 95% CI: 0.63–0.91, P = 0.003) and prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47–0.87, P = 0.005) were shown to be protective against late-onset sepsis. In contrast, longer duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011–1.021, P < 0.0001) and SGA were found to be risk factors (OR: 1.31, 95% CI: 1.02–1.68, P= 0.03).

Conclusions: SGA contributes to the risk of late-onset sepsis in VLBW infants. Future studies are needed to investigate the underlying pathophysiology to guide individualized preventive measures in this vulnerable subgroup.

From the *Department of Pediatrics, University of Lübeck, Lübeck; Department of Pediatrics, University of Magdeburg, Magdeburg; Department of Pediatrics I, University Hospital Essen, University Duisburg, Essen; §Department of Pediatrics, University Homburg, Saar; Department of Neonatology, Children’s Hospital, Dortmund; Department of Pediatrics, University of Düsseldorf, Düsseldorf; **Department of Pediatrics, University of Cologne, Cologne; ††Department of Neonatology, Asklepios Hospital Hamburg-Barmbek, Hamburg; ‡‡Department of Neonatology, Vestische Children´s Hospital, Datteln; §§Department of Neonatology, Vivantes Hospital Berlin-Neukölln, Berlin; ¶¶Department of Pediatrics, Carl Gustav Carus University Dresden, Dresden; ‖‖Department of Neonatology, Children´s Hospital Hannover, Auf der Bult, Hannover; ***Department of Neonatology, Olgahospital Stuttgart; †††Department of Neonatology, Children´s Hospital Hamburg, Altona; and ‡‡‡Department of Neonatology, Children´s Hospital Aschaffenburg, Aschaffenburg, Germany.

Accepted for publication August 23, 2013.

B.T. and W.G. equally contributed to the article.

The authors have no conflicts of interest or funding to disclose.

Address for correspondence: Christoph Härtel, MD, Department of Paediatrics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.