458 - Metabolomic Profile of Extremely Preterm Neonates with a Patent Ductus Arteriosus

Publication Number: 3443.458

Sarah E. Diamond, University of Arkansas for Medical Sciences College of Medicine, Little Rock, AR, United States; Megha Sharma, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Richard W. Hall, UAMS, Little ROck, AR, United States; Hailemariam Abrha Assress, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Renny S. Lan, ACNC, Little Rock, AR, United States; Colin Kay, University of Arkansas for Medical Sciences, Little Rock, AR, United States

Background: A hemodynamically-significant patent ductus arteriosus (hsPDA) is associated with morbidity and mortality in preterm neonates. Early and effective diagnostic methods may help identify neonates needing intervention. However, potential metabolomic biomarkers for the early detection of a PDA are limited. Metabolomics is the study of circulating molecules that are the product of exposures and biochemical pathways, offering powerful insight into the biochemical basis of disease processes. Untargeted metabolomics uses an unsupervised discovery-based approach capturing chemical signatures reflecting differential responses to medical interventions.

Objective: To characterize differences in the metabolic signature of preterm neonates of less than 28 weeks' gestation with a PDA versus those without.

Design/Methods: This was a pilot, prospective, observational study of infants born at less than 28 weeks' gestation. A PDA was diagnosed using echocardiography. Birth samples were presumed to have a PDA based on expected physiology. Blood and urine was collected at up to 5 time points in the first 3 weeks of life. Untargeted metabolomics analysis was performed on urine samples using ultra-high-performance liquid chromatography-coupled mass spectrometry. Data was analyzed for metabolites that differed at time points when a PDA was present versus absent across all samples.

Results: Thirty-two urine samples from 11 patients were processed. The average gestational age was 26.4 weeks and birth weight 706 grams (Table 1). Fifty-two metabolites were significantly different between samples when a PDA was present versus absent (fold change > 2.0, p < 0.05, Figure 1). Metabolites were reviewed for biologic plausibility. A key pathway identified was cholesterol oxidation. Within this pathway, 7-ketocholesterol was found elevated when a PDA was present (Figure 2). 7-ketocholesterol is a product of cholesterol oxidation. It is present in various disease states associated with oxidative stress, inflammation, and cellular damage. It can have cytotoxic effects, and it is a biologically plausible compound for monitoring treatment effectiveness or condition progression.

Conclusion(s): Metabolomics offers an innovative way to examine metabolites associated with a PDA with the hope of discovering potential diagnostic and therapeutic applications.

Table 1. Patient Characteristics.


Figure 1
Volcano plot comparing PDA versus non-PDA samples. Blue points represent metabolites significantly downregulated in PDA samples. Red points represent metabolites significantly upregulated.

Figure 2
Boxplot of 7-ketocholesterol in PDA versus non-PDA samples.