University of Oulu

Outi Aikio, Antti Härmä, Pia Härkin, Markku Leskinen, Marita Valkama, Timo Saarela, Annamari Salminen, Mikko Hallman, Inflammatory biomarkers in very preterm infants during early intravenous paracetamol administration, Early Human Development, Volume 161, 2021, 105464, ISSN 0378-3782,

Inflammatory biomarkers in very preterm infants during early intravenous paracetamol administration

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Author: Aikio, Outi1,2; Härmä, Antti1,2; Härkin, Pia1,2;
Organizations: 1PEDEGO Research Unit and MRC Oulu, University of Oulu, Oulu, Finland
2Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2021-11-10


Background: Paracetamol promotes early closure of patent ductus arteriosus (PDA), and it may affect inflammation after preterm birth.

Objective: The aim of this study was to evaluate the association between paracetamol treatment and serum inflammatory biomarkers in very preterm infants with respiratory distress.

Study design: The infants were randomly assigned to intravenous paracetamol or placebo during the first 4 days of life, and others received a lower dose of paracetamol unblinded. Serum samples were used for the analysis of 10 cytokines, C-reactive protein (CRP) and malondialdehyde (MDA). The impact of paracetamol on the biomarkers was evaluated, based on the levels during the early (<60 h) and the later (60–120 h) postnatal age.

Results: Altogether, 296 serum samples from 31 paracetamol and 25 placebo group infants were analysed. Paracetamol had no effect on cytokine levels during the first 60 h when most induced PDA contractions took place. Later paracetamol treatment was associated with lower serum levels of several cytokines, including interleukin (IL-) 10, interferon gamma-induced protein (IP-) 10, and monocyte chemoattractant protein-1. CRP levels were lower in the paracetamol group during the early treatment. Amongst the infants who had severe morbidities, MDA was higher (p = .045), regardless of paracetamol treatment.

Conclusion: No significant differences in the cytokine levels were evident between the treatment and placebo groups. However, during early treatment, CRP levels were lower in the paracetamol group. To clarify whether this was due to a decrease in cardiopulmonary distress, or a distinct anti-inflammatory effect, requires further studies.

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Series: Early human development
ISSN: 0378-3782
ISSN-E: 1872-6232
ISSN-L: 0378-3782
Volume: 161
Article number: 105464
DOI: 10.1016/j.earlhumdev.2021.105464
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: Present study was supported by grants from following foundations: 1. Foundation for Pediatric Research, Finland (OA, AH). 2. Alma and K.A. Snellman Foundation, Oulu, Finland (OA, AH). 3. Finnish Medical Foundation (OA, AH). 4. Sigrid Jusélius Foundation (MH). The funding foundations had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.
Copyright information: © 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (