JPEN J Parenter Enteral Nutr. 2022 Mar 13. doi: 10.1002/jpen.2374. Online ahead of print.
BACKGROUND: Parenteral nutrition associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, we sought to identify fecal biomarkers, which when integrated with clinical data would better predict risk for developing PNAC.
METHODS: Using untargeted metabolomics in 200 serial stool samples from 60 infants, we applied statistical and machine learning approaches to identify clinical features and metabolic biomarkers with the greatest associative potential for risk of developing PNAC. Stools were collected prospectively from infants receiving parenteral nutrition (PN) with soybean oil-based lipid emulsion at a level IV NICU.
RESULTS: Low birthweight, extreme prematurity, longer duration of PN, and greater number of antibiotic courses were all risk factors for PNAC (p < 0.05). We identified 78 stool biomarkers with early predictive potential (p < 0.05). From these 78 biomarkers, we further identified 12 sphingomyelin lipids with high association for the development of PNAC in pre-cholestasis stool samples when combined with birth anthropometry.
CONCLUSIONS: We demonstrate the potential for stool metabolomics to enhance early identification of PNAC risk. Earlier detection of high-risk infants would empower proactive mitigation with alterations to PN for at-risk infants and optimization of caloric nutrition with PN for infants at lower risk. This article is protected by copyright. All rights reserved.