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Persistent ductus arteriosus in extremely preterm infants
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.ORCID iD: 0000-0001-8382-8687
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 [en]
Echocardiography, Erythropoietin. Extremely preterm infants, Maximal ductal flow velocity, Patent ductus arteriosus, Persistent ductus arteriosus.
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-375550ISBN: 978-91-513-0572-1 (print)OAI: oai:DiVA.org:uu-375550DiVA, id: diva2:1285251
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
List of papers
1. A High Ductal Flow Velocity is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22-27 Weeks Gestational Age
Open this publication in new window or tab >>A High Ductal Flow Velocity is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22-27 Weeks Gestational Age
2012 (English)In: Critical Care Research and Practice, ISSN 2090-1305, E-ISSN 2090-1313, p. 715265-Article in journal (Refereed) Published
Abstract [en]

Objective:

To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22-27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors.

Method:

Infants born at 22-27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory and outcome parameters. Echocardiographic examinations during treatment were reviewed.

Results:

Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25+4 weeks vs. 24+3 weeks; P=0.047), and a higher pre-treatment left to right maximal ductal flow velocity (1.6 m/s vs. 1.1 m/s; P=0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at treatment start, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04, p=0.049).

Conclusion:

Maximal ductal flow velocity was independently associated with success of PDA treatment.

Keywords
patent ductus arteriosus, preterm, cyclooxygenase inhibitors, echocardiography
National Category
Medical and Health Sciences Pediatrics
Identifiers
urn:nbn:se:uu:diva-187783 (URN)10.1155/2012/715265 (DOI)
Funder
Swedish Heart Lung Foundation, 20100033
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2019-02-04Bibliographically approved
2. Early haemodynamically significant patent ductus arteriosus does not predict future persistence in extremely preterm infants
Open this publication in new window or tab >>Early haemodynamically significant patent ductus arteriosus does not predict future persistence in extremely preterm infants
2019 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227Article in journal (Refereed) Accepted
Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
patent ductus arteriosus, echocardiography, ductal flow velocity, extremely preterm infant, haemodynamical significance
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-368852 (URN)10.1111/apa.14752 (DOI)
Available from: 2018-12-08 Created: 2018-12-08 Last updated: 2019-02-11
3. Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation
Open this publication in new window or tab >>Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation
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.

National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-363383 (URN)10.1038/s41390-018-0182-x (DOI)30287890 (PubMedID)
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2019-02-04
4. A matched cohort study of surgical treatment for patent ductus arteriosus in extremely preterm infants
Open this publication in new window or tab >>A matched cohort study of surgical treatment for patent ductus arteriosus in extremely preterm infants
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-375547 (URN)
Available from: 2019-01-30 Created: 2019-01-30 Last updated: 2019-02-04

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Olsson, Karl Wilhelm

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