The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights.
Anna SellmerTine Brink HenriksenJohan PalmfeldtBodil Hammer BechJulie AstonoTue Bjerg BennikeVibeke Elisabeth HjortdalPublished in: Biomolecules (2022)
Complications to preterm birth are numerous, including the presence of a patent ductus arteriosus (PDA). The biological understanding of the PDA is sparse and treatment remains controversial. Herein, we speculate whether the PDA is more than a cardiovascular imbalance, and may be a marker in response to immature core molecular and physiological processes driven by biological systems, such as inflammation. To achieve a new biological understanding of the PDA, we performed echocardiography and collected plasma samples on day 3 of life in 53 consecutively born neonates with a gestational age at birth below 28 completed weeks. The proteome of these samples was analyzed by mass spectrometry (nanoLC-MS/MS) and immunoassay of 17 cytokines and chemokines. We found differences in 21 proteins and 8 cytokines between neonates with a large PDA (>1.5 mm) compared to neonates without a PDA. Amongst others, we found increased levels of angiotensinogen, periostin, pro-inflammatory associations, including interleukin (IL)-1β and IL-8, and anti-inflammatory associations, including IL-1RA and IL-10. Levels of complement factors C8 and carboxypeptidases were decreased. Our findings associate the PDA with the renin-angiotensin-aldosterone system and immune- and complement systems, indicating that PDA goes beyond the persistence of a fetal circulatory connection of the great vessels.
Keyphrases
- gestational age
- preterm birth
- low birth weight
- birth weight
- mass spectrometry
- preterm infants
- ms ms
- oxidative stress
- angiotensin ii
- rheumatoid arthritis
- anti inflammatory
- high resolution
- single molecule
- sensitive detection
- extracorporeal membrane oxygenation
- computed tomography
- ankylosing spondylitis
- liquid chromatography tandem mass spectrometry