493 - Metabolomic Variations in Gastroschisis

Poster Number: 493
Publication Number: 493.424

Tara L. Billings, Loma Linda University Children's Hospital, Bellingham, WA, United States; Adrian Lavery, Loma Linda University Children's Hospital, Loma Linda, CA, United States

Background: Gastroschisis is the most common abdominal wall defect in neonates. Studies show an increased incidence of gastroschisis on both a global and local scale throughout the last few decades. However, the pathophysiology of gastroschisis remains elusive. Uncovering the factors of this pathology may be of value in understanding the basis of disease and devising means for prevention or early treatment.

Objective: This study was undertaken to understand the metabolic differences between cord blood sampled from gastroschisis and control subjects. The main objective of this study was to identify a compound or metabolic pathway that is aberrant in specimens of gastroschisis. Our hope is that if such a pathway can be identified it will lead to understanding the pathophysiology behind gastroschisis.

Design/Methods: A prospective cohort study was performed on cases of gastroschisis and controls at our tertiary care children’s hospital. Study participants were enrolled beginning in 2014, after this study received IRB approval.  Following delivery of the infant, umbilical cord blood was collected and was spun down via centrifugation to obtain plasma. All specimens were stored in a -80° freezer. In total, 46 samples were collected, 23 from gastroschisis patients and 23 from matched controls. Specimens then underwent global metabolic profiling. Welch’s two-sample t-test was used to identify biochemicals that differed significantly between experimental groups.

Results: Comparison of global biochemical profiles for cord blood between gastroschisis and control samples revealed key differences in the metabolome between the two groups. From a high-level view, differences in lipid metabolites drive the separation of the groups. Random forest analysis demonstrated the predicted accuracy between the control and test groups was 93%. The highest number of metabolites on the biochemical importance plot were that of lipid metabolism.Conclusion(s): Differences were noted between the metabolic profiling of cord blood in gastroschisis versus controls. Random forest analysis identified lipid metabolism as a significant source of these differences, identifying multiple lipid-associated metabolites that distinguished between the groups. The impact of these differences remains to be investigated but may reflect differences in cell membrane, umbilical cord wall remodeling, or lipid carriers between groups.  Further investigations into this area may include comparing the metabolic profile of the cord blood with that of the mother and fetus and correlating these metabolites to clinical outcomes.
Random Forest Plot of Lipid MetabolitesEach bubble represents a metabolite. Those that were significantly (p≤0.05) higher or lower in the donor versus the Healthy group are colored red and green, respectively.