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Peer-reviewedCC BY 4.0JAMA Network Open

Umbilical Cord Quantitative Polymerase Chain Reaction and Sepsis Complications for Neonates

59 more authors

60 listed; 71 in total.

6 affiliations
  1. 1Department of Pediatrics, University Hospital Schleswig-Holstein, Lübeck, Germany
  2. 2Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein, Lübeck, Germany
  3. 3Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany
  4. 4German Center for Infection Research Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
  5. 5Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
  6. 6for the German Neonatal Network

Abstract

Importance: Sepsis occurring in the first 72 hours of life is associated with high mortality and complications such as intraventricular hemorrhage (IVH), particularly in preterm infants. Although blood culture is the diagnostic standard, its low detection rate may underestimate the clinical burden of infection.

Objective: To determine whether molecular detection of bacterial DNA in umbilical cord tissue improves identification of preterm infants at risk of sepsis-related death or grade IV IVH.

Design, Setting, and Participants: Samples were collected from infants with a birth weight less than 1500 g between January 2009 and December 2021 in a research network of level 3 neonatal intensive care units (67 sites) and were analyzed by using multiplex quantitative polymerase chain reaction (qPCR) for Enterobacteriaceae and Group B Streptococcus between January 2025 and January 2026. Data analysis occurred from February to March 2026.

Exposures: Positive blood culture results within the first 3 days of life were compared with positive qPCR.

Main Outcome and Measures: Primary outcomes were sepsis-related death within the first 7 days of life and grade IV IVH. Sensitivities were compared and endpoints were assessed by calculating risk ratios and odds ratios (ORs).

Results: Of 30 458 eligible infants, 15 290 were included for analysis (7865 male [51.4%] and 7425 female [48.6%]). Median (IQR) birth weight was 980 (744-1240) g, and median (IQR) gestational age was 28 (26-30) weeks. Blood culture was positive in 90 infants (0.6%), whereas qPCR was positive in 546 infants (3.6%). Within the first week of life, 34 infants (0.2%) died from sepsis and 548 infants (3.6%) developed grade IV IVH. For sepsis-related mortality, umbilical cord qPCR showed a sensitivity of 41.2% (95% CI, 25.6%-59.3%; 14 of 34 infants) compared with 23.5% (95% CI, 10.7%-41.2%; 8 of 34 infants) for blood culture. For grade IV IVH, sensitivity was 8.2% (95% CI, 6.1%-10.9%; 45 of 548 infants) for qPCR and 1.6% (95% CI, 0.8%-3.1%; 9 of 548 infants) for blood culture. The association of positive umbilical cord qPCR with adverse outcome was confirmed after adjustment for known clinical risk factors of sepsis-related mortality (OR, 14.90; 95% CI, 7.26-30.65) and grade IV IVH (OR, 1.89; 95% CI, 1.36-2.64).

Conclusions and Relevance: In this prognostic study of 15 290 preterm infants, umbilical cord vessel qPCR identified twice as many infants who died from sepsis and 5 times as many who developed grade IV IVH compared with blood culture, suggesting that blood culture underestimates the clinical burden of neonatal sepsis.

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BibTeX
@article{hanenberg2026umbilical,
  title = {{Umbilical Cord Quantitative Polymerase Chain Reaction and Sepsis Complications for Neonates}},
  author = {Lisa Hanenberg and Ingmar Fortmann and Jan Rupp and Dennis Nurjadi and Christoph Härtel and Inke Regina König and Wolfgang Göpel and German Neonatal Network and Dirk Müller and Corinna Gebauer and Florian Guthmann and Martin Blohm and Christian Wieg and Ursula Weller and Mark Dzietko and Dirk Olbertz and Anja Stein and Hagen Bayer and Norbert Teig and Michael Hofmann and Knud Linnemann and Susanne Schmidtke and Bettina Bohnhorst and Angela Kribs and Ann-Katrin Hohnecker and Holger Michel and Marie-Claire Detemple and Peter Jahn and Oliver Schroers and Ralf Böttger and Mechthild Hubert and Michael Dördelmann and Georg Hillebrand and Claudia Roll and Reinhard Jensen and Michael Zemlin and Mario Rüdiger and Julia Sandkötter and Ann Carolin Longardt and Stefan Schäger and Florian Kipfmüller and Axel Franz and Malik Aydin and Silke Ehlers and Claudius Werner and Thorsten Orlikowsky and Jürgen Althaus and Katja Schneider and Roland Haase and Thomas Pabst and Fabian Müller and Jana Katharina Dieks and Hans Fuchs and Thorsten Körner and Andreas Müller and Kai Böckenholt and Martin Andree Berghäuser and Hans Proquitté and Patrick Morhart and Jochen Essers},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.37159},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854696},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Umbilical Cord Quantitative Polymerase Chain Reaction and Sepsis Complications for Neonates
AU  - Lisa Hanenberg
AU  - Ingmar Fortmann
AU  - Jan Rupp
AU  - Dennis Nurjadi
AU  - Christoph Härtel
AU  - Inke Regina König
AU  - Wolfgang Göpel
AU  - German Neonatal Network
AU  - Dirk Müller
AU  - Corinna Gebauer
AU  - Florian Guthmann
AU  - Martin Blohm
AU  - Christian Wieg
AU  - Ursula Weller
AU  - Mark Dzietko
AU  - Dirk Olbertz
AU  - Anja Stein
AU  - Hagen Bayer
AU  - Norbert Teig
AU  - Michael Hofmann
AU  - Knud Linnemann
AU  - Susanne Schmidtke
AU  - Bettina Bohnhorst
AU  - Angela Kribs
AU  - Ann-Katrin Hohnecker
AU  - Holger Michel
AU  - Marie-Claire Detemple
AU  - Peter Jahn
AU  - Oliver Schroers
AU  - Ralf Böttger
AU  - Mechthild Hubert
AU  - Michael Dördelmann
AU  - Georg Hillebrand
AU  - Claudia Roll
AU  - Reinhard Jensen
AU  - Michael Zemlin
AU  - Mario Rüdiger
AU  - Julia Sandkötter
AU  - Ann Carolin Longardt
AU  - Stefan Schäger
AU  - Florian Kipfmüller
AU  - Axel Franz
AU  - Malik Aydin
AU  - Silke Ehlers
AU  - Claudius Werner
AU  - Thorsten Orlikowsky
AU  - Jürgen Althaus
AU  - Katja Schneider
AU  - Roland Haase
AU  - Thomas Pabst
AU  - Fabian Müller
AU  - Jana Katharina Dieks
AU  - Hans Fuchs
AU  - Thorsten Körner
AU  - Andreas Müller
AU  - Kai Böckenholt
AU  - Martin Andree Berghäuser
AU  - Hans Proquitté
AU  - Patrick Morhart
AU  - Jochen Essers
PY  - 2026
DA  - 2026/10/01
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.37159
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854696
AB  - Importance: Sepsis occurring in the first 72 hours of life is associated with high mortality and complications such as intraventricular hemorrhage (IVH), particularly in preterm infants. Although blood culture is the diagnostic standard, its low detection rate may underestimate the clinical burden of infection.  Objective: To determine whether molecular detection of bacterial DNA in umbilical cord tissue improves identification of preterm infants at risk of sepsis-related death or grade IV IVH.  Design, Setting, and Participants: Samples were collected from infants with a birth weight less than 1500 g between January 2009 and December 2021 in a research network of level 3 neonatal intensive care units (67 sites) and were analyzed by using multiplex quantitative polymerase chain reaction (qPCR) for Enterobacteriaceae and Group B Streptococcus between January 2025 and January 2026. Data analysis occurred from February to March 2026.  Exposures: Positive blood culture results within the first 3 days of life were compared with positive qPCR.  Main Outcome and Measures: Primary outcomes were sepsis-related death within the first 7 days of life and grade IV IVH. Sensitivities were compared and endpoints were assessed by calculating risk ratios and odds ratios (ORs).  Results: Of 30 458 eligible infants, 15 290 were included for analysis (7865 male [51.4%] and 7425 female [48.6%]). Median (IQR) birth weight was 980 (744-1240) g, and median (IQR) gestational age was 28 (26-30) weeks. Blood culture was positive in 90 infants (0.6%), whereas qPCR was positive in 546 infants (3.6%). Within the first week of life, 34 infants (0.2%) died from sepsis and 548 infants (3.6%) developed grade IV IVH. For sepsis-related mortality, umbilical cord qPCR showed a sensitivity of 41.2% (95% CI, 25.6%-59.3%; 14 of 34 infants) compared with 23.5% (95% CI, 10.7%-41.2%; 8 of 34 infants) for blood culture. For grade IV IVH, sensitivity was 8.2% (95% CI, 6.1%-10.9%; 45 of 548 infants) for qPCR and 1.6% (95% CI, 0.8%-3.1%; 9 of 548 infants) for blood culture. The association of positive umbilical cord qPCR with adverse outcome was confirmed after adjustment for known clinical risk factors of sepsis-related mortality (OR, 14.90; 95% CI, 7.26-30.65) and grade IV IVH (OR, 1.89; 95% CI, 1.36-2.64).  Conclusions and Relevance: In this prognostic study of 15 290 preterm infants, umbilical cord vessel qPCR identified twice as many infants who died from sepsis and 5 times as many who developed grade IV IVH compared with blood culture, suggesting that blood culture underestimates the clinical burden of neonatal sepsis.
SN  - 2574-3805
ER  -