The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants

Abstract

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

Systemic Cytokines in Retinopathy of Prematurity

“…PDA refers to the failure of the ductus arteriosus to close completely 1–2 days after birth [ 262 ]. Prenatal and postnatal infections and the resultant inflammation process have been proposed to contribute greatly to PDA [ 263 ]. Accordingly, elevated levels of cytokines, such as IL-6, IL-8, IL-10, IL-12, growth/differentiation factor 15, MCP-1, and MIP-1α, in cord blood have been reported to be related to the development and persistence of PDA [ 264 , 265 ].…”

Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?

“…This concept of a fetal inflammatory response syndrome (FIRS) with an abnormal fetal immune response and increased levels of proinflammatory cytokines (primarily IL-6) that are insufficiently balanced by immunosuppressive regulators (e.g., IL-10) [ 26 , 27 , 28 , 29 ] is regarded as a first inflammatory event sensitizing for subsequent pre- and postnatal “hits” [ 11 , 30 ]. In the absence of an infectious agent, an inflammatory cascade can be induced in the preterm setting by typical complications of prematurity such as respiratory distress syndrome (RDS), mechanical ventilation, patent ductus arteriosus (PDA), and other hemodynamic disturbances such as intraventricular hemorrhage (IVH) +/− posthemorrhagic ventricular dilatation (PHVD), all of which are accompanied by a prolonged elevation in proinflammatory cytokines [ 31 , 32 , 33 , 34 ].…”

Correlation between the Closure Time of Patent Ductus Arteriosus in Preterm Infants and Long-Term Neurodevelopmental Outcome

“…The ductus arteriosus is a blood vessel that connects the aorta and the pulmonary artery during the fetal period and closes spontaneously 12 to 48 h after birth [1]. During fetal circulation, the ductus arteriosus directs blood flow from the fetal pulmonary artery to the aorta and plays an important role in ensuring oxygen supply during periods when the fetal lungs are immature and lung function is limited [2]. At birth, a decrease in prostaglandin E2 2 of 11 levels, an increase in arterial oxygenation, and a decrease in pulmonary vascular resistance promote the contraction of the ductus arteriosus, forming a fibrous tissue [2].…”