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Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.ORCID iD: 0000-0001-8382-8687
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0003-3161-0402
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
2018 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Place, publisher, year, edition, pages
2018.
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-363383DOI: 10.1038/s41390-018-0182-xPubMedID: 30287890OAI: oai:DiVA.org:uu-363383DiVA, id: diva2:1257104
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2019-02-04
In thesis
1. Persistent ductus arteriosus in extremely preterm infants
Open this publication in new window or tab >>Persistent ductus arteriosus in extremely preterm infants
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patent ductus arteriosus (PDA) is common in infants born <28 weeks gestational age (GA) and associated with significant morbidity. Despite extensive research efforts, the indications for PDA treatment remain controversial. The aims of these studies were to gain knowledge of factors affecting ductal closure during the early postnatal period and provide better means for identification of preterm infants that may benefit from PDA treatment.

In Paper I, infants born <28 weeks GA and pharmacologically treated for PDA were retrospectively identified and their echocardiographic examinations were reviewed. Twenty-nine (52%) infants successfully closed and 27 (48%) infants failed to close PDA during treatment. High maximal ductal flow velocity (Vmax) was independently associated with closure (OR 3.04, p=0.049).

Paper II prospectively included infants born <28 weeks GA and assessed early respiratory, circulatory and echocardiographic parameters. PDA was persistent in 18 (30%) and ultimately closed or insignificant in 42 (70%) infants. Echocardiographic criteria for hemodynamically significant PDA on days 2-7 did not predict persistent PDA (p=1.000). Mechanical ventilation (p=0.025), high mean airway pressure (p=0.020) and low Vmax (p=0.024) during day two were associated with future persistent PDA.

Blood samples were obtained during the second day of life from 47 of the infants in Paper II and serum markers previously associated with PDA or factors affecting PDA were analyzed for Paper III. Inflammatory markers and erythropoietin (EPO) were elevated in infants with future persistent PDA. EPO levels were also higher in infants that did not close PDA during pharmacological treatment.

In Paper IV, 44 infants born <28 weeks GA with surgically ligated PDA were retrospectively compared to non-surgically treated controls. Ligated infants had larger ductal diameter prior to, and lack of diameter decrease after pharmacological treatment for PDA (p=0.048 and p=0.022 respectively), and higher incidence of severe bronchopulmonary dysplasia (p=0.025). Longer periods with invasive ventilation was independently associated with ligation (OR 1.04, p=0.018).

In conclusion, early hsPDA do not predict persistence of ductus arteriosus in extremely preterm infants, but Vmax and EPO are promising early markers for prediction of persistence and should be subjects of future studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 73
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1539
Keywords
Echocardiography, Erythropoietin. Extremely preterm infants, Maximal ductal flow velocity, Patent ductus arteriosus, Persistent ductus arteriosus.
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-375550 (URN)978-91-513-0572-1 (ISBN)
Public defence
2019-03-22, Rosénsalen, Akademiska sjukhuset, Ingång 95/96, NBV, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2019-02-27 Created: 2019-02-04 Last updated: 2019-03-18

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Olsson, Karl WilhelmLarsson, AndersJonzon, AndersSindelar, Richard

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