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VOLUME 2 , ISSUE 2 ( April-June, 2023 ) > List of Articles

ORIGINAL RESEARCH

Enteral Feeding and Antibiotic Treatment Do Not Influence Increased Coefficient of Variation of Total Fecal Bile Acids in Necrotizing Enterocolitis

Janet L Rothers, Christine M Calton, Jennifer MB Stepp, Melissa D Halpern

Keywords : Antibiotics, Bile acids, Baby, Enteral nutrition, Infant, Necrotizing enterocolitis, Newborn, Neonate

Citation Information : Rothers JL, Calton CM, Stepp JM, Halpern MD. Enteral Feeding and Antibiotic Treatment Do Not Influence Increased Coefficient of Variation of Total Fecal Bile Acids in Necrotizing Enterocolitis. 2023; 2 (2):128-132.

DOI: 10.5005/jp-journals-11002-0063

License: CC BY-NC 4.0

Published Online: 05-07-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Introduction: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. In animal models, the accumulation of ileal bile acids (BAs) is a crucial component of NEC pathophysiology. Recently, we showed that the coefficient of variation of total fecal BAs (CV-TBA) was elevated in infants who develop NEC compared to matched controls. However, neither the type of enteral nutrition nor antibiotic treatments—parameters that could potentially influence BA levels—were used to match pairs. Thus, we assessed the relationships between exposure to enteral feeding types and antibiotic treatments with NEC status and CV-TBA. Materials and methods: Serial fecal samples were collected from 79 infants born with birth weight (BW) ≤1800 gm and estimated gestational age (EGA) ≤32 weeks; eighteen of these infants developed NEC. Total fecal BA levels (TBA) were determined using a commercially available enzyme cycling kit. Relationships between CV-TBA and dichotomous variables (NEC status, demographics, early exposure variables) were assessed by independent samples t-tests. Fisher's exact tests were used to assess relationships between NEC status and categorical variables. Results: High values for CV-TBA levels perfectly predicted NEC status among infants in this study. However, feeding type and antibiotic usage did not drive this relationship. Conclusions: As in previous studies, high values for the CV-TBA levels in the first weeks of life perfectly predicted NEC status among infants. Importantly, feeding type and antibiotic usage—previously identified risk factors for NEC—did not drive this relationship.

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  1. Lemons JA, Bauer CR, Oh W, et al. Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics 2001;107(1):E1. DOI: 10.1542/peds.107.1.e1.
  2. Kafetzis DA, Skevaki C, Costalos C. Neonatal necrotizing enterocolitis: an overview. Curr Opin Infect Dis 2003;16(4):349–355. DOI: 10.1097/00001432-200308000-00007.
  3. Israel EJ. Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier. Acta Paediatr Suppl 1994;396:27–32. DOI: 10.1111/j.1651-2227.1994.tb13238.x.
  4. Neu J. Necrotizing enterocolitis: The search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am 1996;43(2):409–432. DOI: 10.1016/s0031-3955(05)70413-2.
  5. de Souza JC, da Motta UI, Ketzer CR. Prognostic factors of mortality in newborns with necrotizing enterocolitis submitted to exploratory laparotomy. J Pediatr Surg 2001;36(3):482–486. DOI: 10.1053/jpsu.2001.21603.
  6. Fitzgibbons SC, Ching Y, Yu D, et al. Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 2009;44(6):1072–1075; discussion 5–6. DOI: 10.1016/j.jpedsurg.2009.02.013.
  7. Thyoka M, de Coppi P, Eaton S, et al. Advanced necrotizing enterocolitis part 1: Mortality. Eur J Pediatr Surg 2012;22(1):8–12. DOI: 10.1055/s-0032-1306263.
  8. Ganapathy V, Hay JW, Kim JH. Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Breastfeed Med 2012;7(1):29–37. DOI: 10.1089/bfm.2011.0002.
  9. Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics 2002;109(3):423–428. DOI: 10.1542/peds.109.3.423.
  10. Vohr BR, Wright LL, Dusick AM, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994. Pediatrics 2000;105(6):1216–1226.
  11. Milovic V, Teller IC, Faust D, et al. Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation. Eur J Clin Invest 2002;32(1):29–34. DOI: 10.1046/j.0014-2972.2001.00938.x.
  12. Craven PA, Pfanstiel J, Saito R, et al. Relationship between loss of rat colonic surface epithelium induced by deoxycholate and initiation of the subsequent proliferative response. Cancer Res 1986;46(11):5754–5759. PMID: 3756920.
  13. Halpern MD, Holubec H, Saunders TA, et al. Bile acids induce ileal damage during experimental necrotizing enterocolitis. Gastroenterology 2006;130(2):359–372. DOI: 10.1053/j.gastro.2005.10.023.
  14. Halpern MD, Weitkamp JH, Patrick SKM, et al. Apical sodium-dependent bile acid transporter upregulation is associated with necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2010;299(3):G623–G631. DOI: 10.1152/ajpgi.00242.2010.
  15. Martin NA, Patrick SKM, Estrada TE, et al. Active transport of bile acids decreases mucin 2 in neonatal ileum: Implications for development of necrotizing enterocolitis. PLoS One 2011;6(12):e27191. DOI: 10.1371/journal.pone.0027191.
  16. Knapp S, Kehring A, Stepp J, et al. Elevated coefficient of variation in total fecal bile acids precedes diagnosis of necrotizing enterocolitis. Sci Rep 2020;10(1):249. DOI: 10.1038/s41598-019-57178-0.
  17. Schanler RJ, Hurst NM, Lau C. The use of human milk and breastfeeding in premature infants. Clin Perinatol 1999;26(2):379–398, vii. PMID: 10394493.
  18. Hammons JL, Jordan WE, Stewart RL, et al. Age and diet effects on fecal bile acids in infants. J Pediatr Gastroenterol Nutr 1988;7(1):30–38. DOI: 10.1097/00005176-198801000-00008.
  19. Caplan MS, Amer M, Jilling T. The role of human milk in necrotizing enterocolitis. Adv Exp Med Biol 2002;503:83–90. DOI: 10.1007/978-1-4615-0559-4_9.
  20. Dvorak B, Halpern MD, Holubec H, et al. Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model. Pediatr Res 2003;53(3):426–433. DOI: 10.1203/01.PDR.0000050657.56817.E0.
  21. Normann E, Fahlen A, Engstrand L, et al. Intestinal microbial profiles in extremely preterm infants with and without necrotizing enterocolitis. Acta Paediatr 2013;102(2):129–136. DOI: 10.1111/apa.12059.
  22. Torrazza RM, Ukhanova M, Wang X, et al. Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis. PLoS One 2013;8(12):e83304. DOI: 10.1371/journal.pone.0083304.
  23. Wang Y, Hoenig JD, Malin KJ, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J 2009;3(8):944–954. DOI: 10.1038/ismej.2009.37.
  24. Stewart CJ, Marrs EC, Magorrian S, et al. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr 2012;101(11):1121–1127. DOI: 10.1111/j.1651-2227.2012.02801.x.
  25. Claud EC, Keegan KP, Brulc JM, et al. Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants. Microbiome 2013;1(1):20. DOI: 10.1186/2049-2618-1-20.
  26. Li M, Wang M, Donovan SM. Early development of the gut microbiome and immune-mediated childhood disorders. Semin Reprod Med 32(1):74–86. DOI: 10.1055/s-0033-1361825.
  27. McMurtry VE, Gupta RW, Tran L, et al. Bacterial diversity and Clostridia abundance decrease with increasing severity of necrotizing enterocolitis. Microbiome 2015;3:11.
  28. Zhou Y, Shan G, Sodergren E, et al. Longitudinal analysis of the premature infant intestinal microbiome prior to necrotizing enterocolitis: A case–control study. PLoS One10(3):e0118632. DOI: 10.1371/journal.pone.0118632.
  29. Ward DV, Scholz M, Zolfo M, et al. Metagenomic sequencing with strain-level resolution implicates uropathogenic E. coli in necrotizing enterocolitis and mortality in preterm infants. Cell Rep 2016;14(12):2912–2924. DOI: 10.1016/j.celrep.2016.03.015.
  30. Bousseboua H, Coz YL, Dabard J, et al. Experimental cecitis in gnotobiotic quails monoassociated with Clostridium butyricum strains isolated from patients with neonatal necrotizing enterocolitis and from healthy newborns. Infect Immun 1989;57(3):932–936. DOI: 10.1128/iai.57.3.932-936.1989.
  31. Sangild PT, Siggers RH, Schmidt M, et al. Diet- and colonization-dependent intestinal dysfunction predisposes to necrotizing enterocolitis in preterm pigs. Gastroenterology 2006;130(6):1776–1792. DOI: 10.1053/j.gastro.2006.02.026.
  32. Velardi AL, Groen AK, Elferink RP, et al. Cell type-dependent effect of phospholipid and cholesterol on bile salt cytotoxicity. Gastroenterology 1991;101(2):457–464. DOI: 10.1016/0016-5085(91)90025-g.
  33. Shekels LL, Beste JE, Ho SB. Tauroursodeoxycholic acid protects in vitro models of human colonic cancer cells from cytotoxic effects of hydrophobic bile acids. J Lab Clin Med 1996;127(1):57–66. DOI: 10.1016/s0022-2143(96)90166-3.
  34. Powell AA, LaRue JM, Batta AK, et al. Bile acid hydrophobicity is correlated with induction of apoptosis and/or growth arrest in HCT116 cells. Biochem J 2001;356(Pt 2):481–486. DOI: 10.1042/0264-6021:3560481.
  35. Caplan MS, Jilling T. New concepts in necrotizing enterocolitis. Curr Opin Pediatr 2001;13(2):111–115. DOI: 10.1097/00008480-200104000-00004.
  36. Uauy RD, Fanaroff AA, Korones SB, et al. Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 1991;119(4):630–638. DOI: 10.1016/s0022-3476(05)82418-7.
  37. Kimura A, Yamakawa R, Ushijima K, et al. Fetal bile acid metabolism during infancy: Analysis of 1 beta-hydroxylated bile acids in urine, meconium and feces. Hepatology 1994;20(4 Pt 1):819–824. DOI: 10.1002/hep.1840200408.
  38. Dominguez KM, Moss RL. Necrotizing enterocolitis. Clin Perinatol 2012;39(2):387–401. DOI: 10.1016/j.clp.2012.04.011.
  39. Rich BS, Dolgin SE. Necrotizing Enterocolitis. Pediatr Rev 2017;38(12):552–559. DOI: 10.1542/pir.2017-0002.
  40. Kudin O, Neu J. Neonatal–perinatal medicine: Diseases of the fetus and infant. 11 ed. Philadelphia, PA: Elsevier; 2020.
  41. Pourcyrous M, Korones SB, Yang W, et al. C-reactive protein in the diagnosis, management, and prognosis of neonatal necrotizing enterocolitis. Pediatrics 2005;116(5):1064–1069. DOI: 10.1542/peds.2004-1806.
  42. Reisinger KW, Kramer BW, Van der Zee DC, et al. Non-invasive serum amyloid A (SAA) measurement and plasma platelets for accurate prediction of surgical intervention in severe necrotizing enterocolitis (NEC). PLoS One 2014;9(6):e90834. DOI: 10.1371/journal.pone.0090834.
  43. Selimoglu MA, Temel I, Yildirim C, et al. The role of fecal calprotectin and lactoferrin in the diagnosis of necrotizing enterocolitis. Pediatr Crit Care Med 2012;13(4):452–454. DOI: 10.1097/PCC.0b013e3182388ae9.
  44. Morecroft JA, Spitz L, Hamilton PA, et al. Plasma cytokine levels in necrotizing enterocolitis. Acta Paediatr Suppl 1994;396:18–20. DOI: 10.1111/j.1651-2227.1994.tb13235.x.
  45. Ng PC, Li K, Wong RP, et al. Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Arch Dis Child Fetal Neonatal Ed 2003;88(3):F209–F213. DOI: 10.1136/fn.88.3.f209.
  46. Benkoe TM, Mechtler TP, Weninger M, et al. Serum levels of interleukin-8 and gut-associated biomarkers in diagnosing necrotizing enterocolitis in preterm infants. J Pediatr Surg 2014;49(10):1446–1451. DOI: 10.1016/j.jpedsurg.2014.03.012.
  47. Stone ML, Tatum PM, Weitkamp JH, et al. Abnormal heart rate characteristics before clinical diagnosis of necrotizing enterocolitis. J Perinatol 2013;33(11):847–850. DOI: 10.1038/jp.2013.63.
  48. Fairchild KD, Lake DE, Kattwinkel J, et al. Vital signs and their cross-correlation in sepsis and NEC: A study of 1,065 very-low-birth-weight infants in two NICUs. Pediatr Res 2017;81(2):315–321. DOI: 10.1038/pr.2016.215.
  49. Sullivan BA, Fairchild KD. Predictive monitoring for sepsis and necrotizing enterocolitis to prevent shock. Semin Fetal Neonatal Med 2015;20(4):255–261. DOI: 10.1016/j.siny.2015.03.006.
  50. Lin YC, Salleb–Aouissi A, Hooven TA. Interpretable prediction of necrotizing enterocolitis from machine learning analysis of premature infant stool microbiota. BMC Bioinformatics 2022;23(1):104. DOI: 10.1186/s12859-022-04618-w.
  51. Sylvester KG, Ling XB, Liu GY, et al. Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants. J Pediatr 2014;164(3):607–612.e1-7. DOI: 10.1016/j.jpeds.2013.10.091.
  52. Torrazza RM, Li N, Young C, et al. Pilot study using proteomics to identify predictive biomarkers of necrotizing enterocolitis from buccal swabs in very low birth weight infants. Neonatology 2013;104(3):234–242. DOI: 10.1159/000353721.
  53. Morrow AL, Lagomarcino AJ, Schibler KR, et al. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants. Microbiome 2013;1(1):13. DOI: 10.1186/2049-2618-1-13.
  54. Stewart CJ, Nelson A, Treumann A, et al. Metabolomic and proteomic analysis of serum from preterm infants with necrotising entercolitis and late-onset sepsis. Pediatr Res 2016;79(3):425–431. DOI: 10.1038/pr.2015.235.
  55. Allison PD. Convergence Failures in Logistic Regression. Proceedings of the SAS Global Forum 2008 Conference. 2008;360 (1).
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