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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pediatr. | doi: 10.3389/fped.2019.00212

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

 María Carmen Bravo1*, Paloma López2,  Laura Sánchez1, Rosario Madero1, Fernando Cabañas3, Armin Koch4,  Héctor Rojas5, Heike Rabe5 and Adelina Pellicer1
  • 1University Hospital La Paz, Spain
  • 2Hospital Infantil La Paz, Spain
  • 3Hospital Universitario Quirónsalud Madrid, Spain
  • 4Institut für Zellbiochemie, Medizinische Hochschule Hannover, Germany
  • 5Brighton and Sussex Medical School, University of Sussex, United Kingdom

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 moderatesevere

brain damage by cranial ultrasound at term equivalent) of these biomarkers was


Study Design. Retrospective data analysis from preterm infants enrolled in a placebocontrolled

trial on dobutamine for low superior vena cava (SVC) flow, who showed

normal SVC flow within the first 24h (not randomised). Five positive biomarkers were

considered: MABP < gestational age (GA)-1 mmHg; MABP 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 (2-95h).

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=.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 towards 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

towards 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.

Keywords: Transitional circulation, preterm, Cardiovascular treatment, Hypotension, Circulatory impairment

Received: 03 Dec 2018; Accepted: 10 May 2019.

Edited by:

Michael P. Meyer, Kidz First Middlemore Hospital, New Zealand

Reviewed by:

Anup C. Katheria, Sharp Mary Birch Hospital for Women & Newborns, United States
Himanshu Popat, Children's Hospital at Westmead, Australia  

Copyright: © 2019 Bravo, López, Sánchez, Madero, Cabañas, Koch, Rojas, 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.

* Correspondence: Dr. María Carmen Bravo, University Hospital La Paz, La Paz, Spain,