634 - Does Prolonged Use of Parenteral Nutrition Alter Bile Acid Levels in Neonates?

Publication Number: 1611.634

Wenona Lok, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, United States; Elizabeth A. Eckman, MidAtlantic Neonatology Associates, Morristown, NJ, United States; Nathaniel Jackson, Northwell Cohen Children's Medical Center - - New Hyde Park, NY - 430 Lakeville RoadNew Hyde Park, NY 11040UNITED STATES - New Hyde Park, NY, Floral park, NY, United States; Mariana Brewer, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, NEW HYDE PARK, NY, United States; Naureen Memon, Goryeb Children's Hospital, Morristown, NJ, United States; Barry Weinberger, Cohen Children's Medical Center, New Hyde Park, NY, United States

Background: Parenteral nutrition (PN) is essential in the NICU for the growth and survival of premature infants who cannot tolerate enteral feeds and term infants with intestinal failure, but long-term use of PN can lead to parenteral nutrition-associated liver disease (PNALD). Although PNALD generally reverses after feeding is established, it can progress to chronic liver failure. The secretion of bile acids (BA) from the liver is typically impaired in PNALD, and accumulation of BA in the liver exacerbates hepatocellular injury. Early diagnosis of PNALD is important because timely palliative interventions can improve outcomes. Serum conjugated bilirubin is the most used marker, but it is only an indirect measure of perturbations of BA metabolism. Serum and stool BA levels are useful biomarkers of impending cholestasis in various pediatric and adult conditions, but their utility in the diagnosis of PNALD is not known.

Objective: To determine whether exposure of neonates to PN for 14 days alters BA concentrations in the serum and stool at 14, 28, and 42 days.

Design/Methods: In this prospective case-control study, the case group (n=23) was defined as infants on PN on day 14. Infants in the control group (n=15) were matched for sex and gestational age but had not received more than 8 days of PN. Blood and stool were sampled at 14, 28, and 42 +/- 3 days when available. Stool was diluted 1:100 in extract buffer prior to analysis. Total BA in serum and stool extracts were analyzed in duplicate using an enzymatic colorimetric assay. Data were compared using T tests or Mann-Whitney U tests.

Results: The gestational ages in the control and case groups were 31 (28-37) and 29 (26-34) weeks respectively [median (IQR), p=0.2]. Median days on PN were 7 and 21 in the control and case groups, respectively (p < 0.0001). BA concentrations were not significantly different between the groups at 14 days in serum [12.0 (7.3-38.3) µmol/L in control vs 22.5 (8.6-36.8) in case, p=0.32] or stool [218.2 (182.4-320.2) in control vs 320.9 (183.3-1191.0) in case, p=0.17]. Similarly, no significant alterations in serum or stool BA concentrations were seen at 28 or 42 days (Figures 1 and 2).

Conclusion(s): Total serum and stool BA levels do not differ significantly between neonates receiving 14 days of PN and controls, suggesting that total BA concentrations may not be an early marker of impending PNALD. It is possible that specific (rather than total) BA are altered by PN, or that longer periods of exposure to PN are required to impact BA concentrations.

Serum BA Concentrations
Figure 1. Comparison of bile acid concentrations in serum between infants receiving prolonged parenteral nutrition and controls on day of life 14, 28, and 42. Boxes represent 25th-75th percentiles; line, median; whiskers, range (minimum to maximum).

Stool BA Concentrations
Figure 2. Comparison of bile acid concentrations in stool between infants receiving prolonged parenteral nutrition and controls on day of life 14, 28, and 42. Boxes represent 25th-75th percentiles; line, median; whiskers, range (minimum to maximum).