Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation



Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.


Infants born at 22–27 weeks’ gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.


High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.


High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

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The authors would like to thank Viktoria Nelin for the suggestions regarding the English language, and the nurses at the Neonatal Intensive Care Unit, Uppsala University Children’s Hospital, Uppsala, and especially the research nurse Cecilia Ewald for her assistance in the collection of blood samples. This study was supported by grants from the Royal Society of Arts and Sciences of Uppsala; Födelsefonden/Perinatalmedicinska Forskningsfonden, Uppsala; the Samariten Foundation for Paediatric Research, Stockholm; Crown Princess Lovisa’s Foundation for Children’s Health Care, Stockholm; the Center for Clinical Research Dalarna; and the Uppsala-Örebro Regional Research Council.

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K.W.O.: conceptualized and designed the study, supervised data collection, designed the custom data handling software, drafted the initial manuscript, and approved the final manuscript as submitted. A.L.: conceptualized and designed the study, carried out analyses of endothelin-1 and thromboxane B2, reviewed and revised the manuscript, and approved the final manuscript as submitted. A.J.: conceptualized and designed the study, carried out the echocardiographic examinations, supervised data collection, reviewed and revised the manuscript, and approved the final manuscript as submitted. R.S.: conceptualized and designed the study, coordinated and supervised data collection, reviewed and revised the manuscript, and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Karl Wilhelm Olsson.

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Olsson, K.W., Larsson, A., Jonzon, A. et al. Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation. Pediatr Res 86, 333–338 (2019). https://doi.org/10.1038/s41390-018-0182-x

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