Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study

Sofia el Manouni el Hassani, Daniel J. C. Berkhout, Hendrik J. Niemarkt, Sarah Mann, Willem P. de Boode, Veerle Cossey, Christian V. Hulzebos, Anton H. van Kaam, Boris W. Kramer, Richard A. van Lingen, Johannes B. van Goudoever, Daniel C. Vijlbrief, Mirjam M. van Weissenbruch, Marc A. Benninga, Nanne K. H. de Boer, Tim G. J. de Meij

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Late-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS. Objectives: The aim was to identify risk factors for LOS. Methods: In this multicenter case-control study, preterm infants born at ≤30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1: 1 matched case-control cohort. Results: In total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95% CI 1.07-1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95% CI 0.01-0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95% CI 1.257-11.363; p = 0.018). Conclusion: The length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.
Original languageEnglish
JournalNeonatology
DOIs
Publication statusPublished - 2019

Cite this

el Manouni el Hassani, Sofia ; Berkhout, Daniel J. C. ; Niemarkt, Hendrik J. ; Mann, Sarah ; de Boode, Willem P. ; Cossey, Veerle ; Hulzebos, Christian V. ; van Kaam, Anton H. ; Kramer, Boris W. ; van Lingen, Richard A. ; van Goudoever, Johannes B. ; Vijlbrief, Daniel C. ; van Weissenbruch, Mirjam M. ; Benninga, Marc A. ; de Boer, Nanne K. H. ; de Meij, Tim G. J. / Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study. In: Neonatology. 2019.
@article{757463c01bad4371aa35efb4073c0e58,
title = "Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study",
abstract = "Background: Late-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS. Objectives: The aim was to identify risk factors for LOS. Methods: In this multicenter case-control study, preterm infants born at ≤30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1: 1 matched case-control cohort. Results: In total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95{\%} CI 1.07-1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95{\%} CI 0.01-0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95{\%} CI 1.257-11.363; p = 0.018). Conclusion: The length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.",
author = "{el Manouni el Hassani}, Sofia and Berkhout, {Daniel J. C.} and Niemarkt, {Hendrik J.} and Sarah Mann and {de Boode}, {Willem P.} and Veerle Cossey and Hulzebos, {Christian V.} and {van Kaam}, {Anton H.} and Kramer, {Boris W.} and {van Lingen}, {Richard A.} and {van Goudoever}, {Johannes B.} and Vijlbrief, {Daniel C.} and {van Weissenbruch}, {Mirjam M.} and Benninga, {Marc A.} and {de Boer}, {Nanne K. H.} and {de Meij}, {Tim G. J.}",
year = "2019",
doi = "10.1159/000497781",
language = "English",
journal = "Neonatology",
issn = "1661-7800",
publisher = "S. Karger AG",

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Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study. / el Manouni el Hassani, Sofia; Berkhout, Daniel J. C.; Niemarkt, Hendrik J.; Mann, Sarah; de Boode, Willem P.; Cossey, Veerle; Hulzebos, Christian V.; van Kaam, Anton H.; Kramer, Boris W.; van Lingen, Richard A.; van Goudoever, Johannes B.; Vijlbrief, Daniel C.; van Weissenbruch, Mirjam M.; Benninga, Marc A.; de Boer, Nanne K. H.; de Meij, Tim G. J.

In: Neonatology, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Risk Factors for Late-Onset Sepsis in Preterm Infants: A Multicenter Case-Control Study

AU - el Manouni el Hassani, Sofia

AU - Berkhout, Daniel J. C.

AU - Niemarkt, Hendrik J.

AU - Mann, Sarah

AU - de Boode, Willem P.

AU - Cossey, Veerle

AU - Hulzebos, Christian V.

AU - van Kaam, Anton H.

AU - Kramer, Boris W.

AU - van Lingen, Richard A.

AU - van Goudoever, Johannes B.

AU - Vijlbrief, Daniel C.

AU - van Weissenbruch, Mirjam M.

AU - Benninga, Marc A.

AU - de Boer, Nanne K. H.

AU - de Meij, Tim G. J.

PY - 2019

Y1 - 2019

N2 - Background: Late-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS. Objectives: The aim was to identify risk factors for LOS. Methods: In this multicenter case-control study, preterm infants born at ≤30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1: 1 matched case-control cohort. Results: In total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95% CI 1.07-1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95% CI 0.01-0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95% CI 1.257-11.363; p = 0.018). Conclusion: The length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.

AB - Background: Late-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS. Objectives: The aim was to identify risk factors for LOS. Methods: In this multicenter case-control study, preterm infants born at ≤30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1: 1 matched case-control cohort. Results: In total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95% CI 1.07-1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95% CI 0.01-0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95% CI 1.257-11.363; p = 0.018). Conclusion: The length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064059163&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30947195

U2 - 10.1159/000497781

DO - 10.1159/000497781

M3 - Article

JO - Neonatology

JF - Neonatology

SN - 1661-7800

ER -