214 - Elevation of IL-6, IL-8, TNF-a, and VEGF is associated with a hemodynamically significant PDA in the first three days of life in extremely premature infants

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 214
Publication Number: 214.329

Timothy J. Boly, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Stephania Cavallaro Moronta, University of Iowa Stead Family Children's Hospital, Coralville, IA, United States; Patrick J. McNamara, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States; Jennifer Bermick, University of Iowa, Iowa City, IA, United States

Presenting Author(s)

Timothy J. Boly, DO (he/him/his)

Fellow Physician
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, United States

Background: Hemodynamically significant patent ductus arteriosus (hsPDA) has been associated with many adverse outcomes in extremely premature infants, including bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis. Factors that lead to a hsPDA and its continued patency in this population are incompletely understood.

Objective: To evaluate the role of pro-inflammatory cytokines in maintaining the patency of the ductus arteriosus in extremely premature infants in the first postnatal week.

Design/Methods: Residual serum samples were collected from extremely premature infants (22-26 weeks’ gestation). Multiplex protein analysis was performed to assess for serum levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70, CCL2, PDGF, TNF-α, and VEGF prior to 24 hours of life and at 24, 72, and 168 hours. Infants underwent serial targeted neonatal echocardiography (TnEcho) on days 1, 3, and 7 per unit protocol. Infants were divided into those with hsPDA requiring treatment (determined by Iowa PDA Score) and those without hsPDA. Secondary analysis was performed on those with insignificant PDA to determine if serum cytokine levels could be associated with a hsPDA on the next TnEcho.

Results: 52 infants were included in the initial collection. Two infants were excluded from analysis as ductal patency was associated with pathologic pulmonary hypertension. Elevation of IL-8 was associated with hsPDA in the first 24 postnatal hours (Figure 1). By 24 postnatal hours, elevation of IL-8, IL-10, CCL2, and VEGF were positively associated with hsPDA (Figure 1). Interestingly, elevation of IL-1β was associated with an insignificant PDA at the first two timepoints (Figure 1). By 72 hours, elevation of IL-1β, IL-6, and TNF-α were associated with hsPDA (Figure 1). There were no significant differences at 168 hours. For patients with an insignificant PDA, elevation of IL-6 at 24 hours and IL-1β at 72 hours was associated with the presence of a hsPDA on the next TnEcho (Figure 2).

Conclusion(s): Elevation of pro-inflammatory cytokines in the first 3 postnatal days is significantly associated with patency of the ductus arteriosus. Early life inflammation, such as chorioamnionitis and early-onset sepsis, may be considered risk factors for hsPDA requiring treatment. Further work is needed to examine the direct effect of pro-inflammatory cytokines on ductal tissue.