Validity of biomarkers of early circulatory impairment to predict outcome: A retrospective analysis

NeoCirculation Consortium (NEO-CIRC)

doi:10.3389/fped.2019.00212

Validity of biomarkers of early circulatory impairment to predict outcome: A retrospective analysis

NeoCirculation Consortium (NEO-CIRC)

Clinic of Pediatric and Adolescent Medicine

7 Citations (Scopus)

Abstract

Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < −9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.

Original language	English
Article number	212
Journal	Frontiers in Pediatrics
Volume	7
Issue number	MAY
DOIs	https://doi.org/10.3389/fped.2019.00212
Publication status	Published - 2019

Funding

This study has been performed as part of the NEO-CIRCulation Project. The work was partially supported by NEO-CIRC FP7-HEALTH grant (agreement no: 282533). This study has been performed as part of the NEO-CIRCulation Project. The work was partially supported by NEO-CIRC FP7-HEALTH grant (agreement no: 282533). We thank the partners of the NEO-CIRC consortium for their ongoing scientific discussions of the topic (Chief Investigator: AP, Madrid, Spain. Principal Project Coordinator: HR, Brighton, UK. Local Investigators: Philip Amess, Neil Aiton, David Crook, Ramon Fernandez-Alvarez, Liam Mahoney, HR, Rebecca Ramsay, HR-A, Sonia Sobowiec Kouman, Brighton, UK; Vincent Jullien, Thomas Le Saux, Gerard Pons, Sarah Zohar, Paris, France; Frank Biertz, Marjan Brinkhaus, AK, Andrea Smith, Yvonne Ziert, Hannover, Germany; Jon Lopez Heredia, Maria Cruz Lopez Herrera, Victoria Mielgo, Bizkaia, Spain; Wolfgang Göpel, Christoph Härtel, Lübeck, Germany; Charalampos Kotidis, Mark Turner, Michael Weindling, Liverpool, UK; Claudia Roll, Datteln, Germany; Maria del Carmen Bravo, FC, PL-O, LS, Marta Pavía, AP, Madrid, Spain; Clare Gleeson, Simon Bryson, Manchester, UK; MelindaMatyas, Gabriela Zaharie, Cluj-Napoca, Romania; Géza Bokodi, Miklós Szabó, Budapest, Hungary; Tibor Ertl, Simone Funke, Pécs, Hungary; Ebru Ergenekon,

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 5 Gender Equality

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

Access to Document

10.3389/fped.2019.00212

Cite this

@article{19cb6d46c3b5435ba6944b8e04f5790e,

title = "Validity of biomarkers of early circulatory impairment to predict outcome: A retrospective analysis",

abstract = "Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < −9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95\%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.",

author = "\{NeoCirculation Consortium (NEO-CIRC)\} and Bravo, \{Mar{\'i}a Carmen\} and Paloma L{\'o}pez-Ortego and Laura S{\'a}nchez and Rosario Madero and Fernando Caba{\~n}as and Armin Koch and H{\'e}ctor Rojas-Anaya and Heike Rabe and Adelina Pellicer and Philip Amess and Neil Aiton and David Crook and Ramon Fernandez-Alvarez and Liam Mahoney and Rebecca Ramsay and Kouman, \{Sonia Sobowiec\} and Vincent Jullien and \{Le Saux\}, Thomas and Gerard Pons and Sarah Zohar and Frank Biertz and Marjan Brinkhaus and Andrea Smith and Yvonne Ziert and Heredia, \{Jon Lopez\} and Herrera, \{Maria Cruz Lopez\} and Victoria Mielgo and Wolfgang G{\"o}pel and Christoph H{\"a}rtel and Charalampos Kotidis and Mark Turner and Michael Weindling and Claudia Roll and Marta Pav{\'i}a and Clare Gleeson and Simon Bryson and Melinda Matyas and Gabriela Zaharie and G{\'e}za Bokodi and Mikl{\'o}s Szab{\'o} and Tibor Ertl and Simone Funke and Ebru Ergenekon and Kivilcim G{\"u}c{\"u}yener and Ebnem Soysal and Christiane Dammann and Raju, \{Tonse N.K.\} and Nicholas Evans and Stephanie L{\"a}er and Silke Mader",

note = "Funding Information: This study has been performed as part of the NEO-CIRCulation Project. The work was partially supported by NEO-CIRC FP7-HEALTH grant (agreement no: 282533). Funding Information: This study has been performed as part of the NEO-CIRCulation Project. The work was partially supported by NEO-CIRC FP7-HEALTH grant (agreement no: 282533). We thank the partners of the NEO-CIRC consortium for their ongoing scientific discussions of the topic (Chief Investigator: AP, Madrid, Spain. Principal Project Coordinator: HR, Brighton, UK. Local Investigators: Philip Amess, Neil Aiton, David Crook, Ramon Fernandez-Alvarez, Liam Mahoney, HR, Rebecca Ramsay, HR-A, Sonia Sobowiec Kouman, Brighton, UK; Vincent Jullien, Thomas Le Saux, Gerard Pons, Sarah Zohar, Paris, France; Frank Biertz, Marjan Brinkhaus, AK, Andrea Smith, Yvonne Ziert, Hannover, Germany; Jon Lopez Heredia, Maria Cruz Lopez Herrera, Victoria Mielgo, Bizkaia, Spain; Wolfgang G{\"o}pel, Christoph H{\"a}rtel, L{\"u}beck, Germany; Charalampos Kotidis, Mark Turner, Michael Weindling, Liverpool, UK; Claudia Roll, Datteln, Germany; Maria del Carmen Bravo, FC, PL-O, LS, Marta Pav{\'i}a, AP, Madrid, Spain; Clare Gleeson, Simon Bryson, Manchester, UK; MelindaMatyas, Gabriela Zaharie, Cluj-Napoca, Romania; G{\'e}za Bokodi, Mikl{\'o}s Szab{\'o}, Budapest, Hungary; Tibor Ertl, Simone Funke, P{\'e}cs, Hungary; Ebru Ergenekon, Publisher Copyright: Copyright {\textcopyright} 2019 Bravo, L{\'o}pez-Ortego, S{\'a}nchez, Madero, Caba{\~n}as, Koch, Rojas-Anaya, Rabe and Pellicer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

doi = "10.3389/fped.2019.00212",

language = "English",

volume = "7",

journal = "Frontiers in Pediatrics",

number = "MAY",

}

TY - JOUR

T1 - Validity of biomarkers of early circulatory impairment to predict outcome: A retrospective analysis

AU - NeoCirculation Consortium (NEO-CIRC)

AU - Bravo, María Carmen

AU - López-Ortego, Paloma

AU - Sánchez, Laura

AU - Madero, Rosario

AU - Cabañas, Fernando

AU - Koch, Armin

AU - Rojas-Anaya, Héctor

AU - Rabe, Heike

AU - Pellicer, Adelina

AU - Amess, Philip

AU - Aiton, Neil

AU - Crook, David

AU - Fernandez-Alvarez, Ramon

AU - Mahoney, Liam

AU - Ramsay, Rebecca

AU - Kouman, Sonia Sobowiec

AU - Jullien, Vincent

AU - Le Saux, Thomas

AU - Pons, Gerard

AU - Zohar, Sarah

AU - Biertz, Frank

AU - Brinkhaus, Marjan

AU - Smith, Andrea

AU - Ziert, Yvonne

AU - Heredia, Jon Lopez

AU - Herrera, Maria Cruz Lopez

AU - Mielgo, Victoria

AU - Göpel, Wolfgang

AU - Härtel, Christoph

AU - Kotidis, Charalampos

AU - Turner, Mark

AU - Weindling, Michael

AU - Roll, Claudia

AU - Pavía, Marta

AU - Gleeson, Clare

AU - Bryson, Simon

AU - Matyas, Melinda

AU - Zaharie, Gabriela

AU - Bokodi, Géza

AU - Szabó, Miklós

AU - Ertl, Tibor

AU - Funke, Simone

AU - Ergenekon, Ebru

AU - Gücüyener, Kivilcim

AU - Soysal, Ebnem

AU - Dammann, Christiane

AU - Raju, Tonse N.K.

AU - Evans, Nicholas

AU - Läer, Stephanie

AU - Mader, Silke

N1 - Funding Information: This study has been performed as part of the NEO-CIRCulation Project. The work was partially supported by NEO-CIRC FP7-HEALTH grant (agreement no: 282533). Funding Information: This study has been performed as part of the NEO-CIRCulation Project. The work was partially supported by NEO-CIRC FP7-HEALTH grant (agreement no: 282533). We thank the partners of the NEO-CIRC consortium for their ongoing scientific discussions of the topic (Chief Investigator: AP, Madrid, Spain. Principal Project Coordinator: HR, Brighton, UK. Local Investigators: Philip Amess, Neil Aiton, David Crook, Ramon Fernandez-Alvarez, Liam Mahoney, HR, Rebecca Ramsay, HR-A, Sonia Sobowiec Kouman, Brighton, UK; Vincent Jullien, Thomas Le Saux, Gerard Pons, Sarah Zohar, Paris, France; Frank Biertz, Marjan Brinkhaus, AK, Andrea Smith, Yvonne Ziert, Hannover, Germany; Jon Lopez Heredia, Maria Cruz Lopez Herrera, Victoria Mielgo, Bizkaia, Spain; Wolfgang Göpel, Christoph Härtel, Lübeck, Germany; Charalampos Kotidis, Mark Turner, Michael Weindling, Liverpool, UK; Claudia Roll, Datteln, Germany; Maria del Carmen Bravo, FC, PL-O, LS, Marta Pavía, AP, Madrid, Spain; Clare Gleeson, Simon Bryson, Manchester, UK; MelindaMatyas, Gabriela Zaharie, Cluj-Napoca, Romania; Géza Bokodi, Miklós Szabó, Budapest, Hungary; Tibor Ertl, Simone Funke, Pécs, Hungary; Ebru Ergenekon, Publisher Copyright: Copyright © 2019 Bravo, López-Ortego, Sánchez, Madero, Cabañas, Koch, Rojas-Anaya, Rabe and Pellicer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019

Y1 - 2019

N2 - Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < −9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.

AB - Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < −9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.

UR - https://www.scopus.com/pages/publications/85067437167

U2 - 10.3389/fped.2019.00212

DO - 10.3389/fped.2019.00212

M3 - Journal articles

AN - SCOPUS:85067437167

VL - 7

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

IS - MAY

M1 - 212

ER -

Validity of biomarkers of early circulatory impairment to predict outcome: A retrospective analysis

Abstract

Funding

UN SDGs

Research Areas and Centers

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