340 - Early Intravenous Lipid Use is Associated with Transient Elevation of Total Fecal Bile Acids in Pre-Term Infants

Publication Number: 3327.340

Christine M. Calton, University of Arizona College of Medicine, Tucson, AZ, United States; Shannon L. Gutenkunst, University of Arizona, Tucson, AZ, United States; Madeleine T. McKay, Banner Health, Tucson, AZ, United States; Samantha Economos Frank, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, United States; Harrison J. Moody, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, United States; Isaac Molina, University Arizona College of Medicine, Tucson, AZ, United States; Aparna Chandrasekar, University Arizona College of Medicine, Phoenix, AZ, United States; Joern-Hendrik Weitkamp, Vanderbilt University School of Medicine, Nashville, TN, United States; Melissa D. Halpern, University of Arizona, Tucson, AZ, United States

Background: The coefficient of variation (Co-V) of fecal total bile acids (FTBA) is elevated in pre-term infants (PTI) who later develop necrotizing enterocolitis (NEC) and has been suggested as a predictor for NEC. However, FTBA can be influenced by nutritional lipids which could limit its utility as a NEC biomarker. While much is known about comorbidities associated with long-term total parenteral nutrition (TPN) use in PTI, effects of short-term TPN exposure on FTBA have not been widely examined.

Objective: Because many PTI receive TPN and intravenous lipids (IL) only in the first weeks postpartum, the goal of this study was to determine how this practice affects FTBA.

Design/Methods: Thirty-three PTI were enrolled under approval by the Institutional Review Boards at Banner University Hospital, Tucson, AZ (n=19) and Vanderbilt University Medical Center, Nashville, TN (n=14). FTBA levels were analyzed in non-meconium samples during and after their first exposure to TPN/IL using the Diazyme Total Bile Acids Kit. Inclusion criteria were availability of at least 2 FTBA measurements during TPN/IL, at least 2 measurements in the 5 days following TPN/IL cessation, and no TPN/IL restart within that window. Short-term exposure was defined as receiving TPN/IL for only the first weeks of life. An additional 13 infants who did not receive TPN/IL (No TPN/IL) were used for comparison (Table 1). No infants in either group developed NEC. Linear mixed effects models were used to compare geometric mean FTBA levels during and after TPN/IL. Results are presented for both an unadjusted mixed model (UAMM) and a model adjusted for fortifier use and gestational age (AMM), which were selected as covariates based on their potential influence on bile acid metabolism in PTI.

Results: FTBA levels were significantly elevated during TPN/IL compared to after TPN/IL cessation (Table 2). The AMM found a 55% elevation in TBA levels during TPN/IL. The UAMM showed a slightly stronger effect-68% elevation-indicating that while fortifier supplementation and/or gestational age partially explain the TPN/IL-associated elevation, a substantial effect remains. The No TPN/IL group showed no significant change in TBA levels in either UAMM or AMM (data not shown).

Conclusion(s): Short-term TPN/IL administration is associated with elevated FTBA, with levels decreasing following TPN/IL cessation. While further studies using a larger cohort of infants are underway, these findings suggest that the Co-V of FTBA is unlikely to be influenced by short-term exposure to TPN/IL, enhancing its potential as a NEC prediction biomarker.

Table 1. Demographics of Infants by Group.
1 n (%)
2 Mean ± SD (min - max)
3 Fisher's exact test, Wilcoxon rank sum test
4 Mean ± SD (min - max) percentage of measurement days where fortifier was given for each infant.
# More than one race could be selected for each infant; % may not sum to 100%.
& For each infant, the percentage of measurement days was calculated where fortifier was given. In the TPN/IL group, this was calculated separately during TPN/IL administration and after TPN/IL cessation. For the No TPN/IL group, this was calculated separately for Early (≤10 days) and Late (>10 days) periods.

Table 2. Comparisons of FTBA During and After TPN/IL