Fecal calprotectin, lactoferrin and morbidity associated with immature digestive tract in preterm infants
DOI:
https://doi.org/10.15574/SP.2022.127.38Keywords:
fecal calprotectin, lactoferrin, neonatal sepsis, necrotizing enterocolitis, preterm infantsAbstract
Introduction. Excessive intestinal inflammation in preterm infants is one of the key factors in the development of necrotizing enterocolitis (NEC), early- (EOS) and late-onset neonatal sepsis (LOS).
Purpose - to evaluate the connection between fecal calprotectin (FC), enteral use of lactoferrin (LF), and the occurrence of NEC, EOS, and LOS in preterm infants.
Materials and methods. FC was measured in 26 newborns with gestational age (GA) ≤32 weeks and birth weight ≤1500 g. Feces were collected twice: in the first 7 days of life and at the postmenstrual age (PMA) of 36 weeks. The main group included 15 infants with either EOS, LOS or NEC. The remaining 11 infants formed the comparison group. Eleven infants received LF (4 in the main group and 7 in the comparison group), which was randomly administered in the first 3 days of life.
Results. FC in the first 7 days of life was higher in the main group (р>0.05). At the PMA of 36 weeks, FC decreased in the main group and increased in the comparison group (p>0.05). FC in the first week of life was higher in infants with EOS compared to newborns without the diseases (p=0.03), followed by a decrease at the PMA of 36 weeks (p=0.04). There was no significant difference in FC levels depending on the development of LOS or NEC. FC levels increased in all infants who received LF and decreased in babies who did not receive LF (p>0.05).
Conclusions. The occurrence of EOS is associated with a significant increase in FC which subsequently decrease by the PMA of 36 weeks. FC in the first week of life are not associated with the development of NEC or LOS. Enteral use of LF at a dose of 100 mg/day is associated with an increase in FC levels (p>0.05).
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
References
Aadland E, Fagerhol MK. (2002). Faecal calprotectin: a marker of inflammation throughout the intestinal tract. European Journal of Gastroenterology & Hepatology. 14 (8): 823-825. https://doi.org/10.1097/00042737-200208000-00002; PMid:12172400
Asgarshirazi M, Shariat M, Nayeri F, Dalili H, Abdollahi A. (2017). Comparison of Fecal Calprotectin in Exclusively Breastfed and Formula or Mixed Fed Infants in the First Six Months of Life. Acta Med Iran. 55: 1. https://doi.org/10.5812/compreped.59992
Aydemir O, Aydemir C, Sarikabadayi YU, Emre Canpolat F, Erdeve O, Biyikli Z, Dilmen U. (2012). Fecal calprotectin levels are increased in infants with necrotizing enterocolitis. The Journal of Maternal-Fetal & Neonatal Medicine. 25 (11): 2237-2241. https://doi.org/10.3109/14767058.2012.684172; PMid:22524488
Decembrino L, De Amici M, Pozzi M, De Silvestri A, Stronati M. (2015). Serum Calprotectin: A Potential Biomarker for Neonatal Sepsis. Journal of Immunology Research. 2015: 1-4. https://doi.org/10.1155/2015/147973; PMid:26380313 PMCid:PMC4563108
Dobryk D, Dobryk O, Dobryanskyy D. (2022). The effect of enteral lactoferrin supplementation in prevention of morbidity associated with immature digestive tract in premature infants: prospective cohort study. Georgian Medical News. 323: 94-101. URL: http://www.ncbi.nlm.nih.gov/pubmed/35271478.
Ewaschuk JB, Unger S, O'Connor DL, Stone D, Harvey S, Clandinin MT, Field CJ. (2011). Effect of pasteurization on selected immune components of donated human breast milk. Journal of Perinatology. 31 (9): 593-598. https://doi.org/10.1038/jp.2010.209; PMid:21330996
Groer M, Ashmeade T, Louis-Jacques A, Beckstead J, Ji M. (2016). Relationships of Feeding and Mother's Own Milk with Fecal Calprotectin Levels in Preterm Infants. Breastfeeding Medicine. 11 (4): 207-212. https://doi.org/10.1089/bfm.2015.0115; PMid:27002351 PMCid:PMC4860673
Johne B, Fagerhol MK, Lyberg T, Prydz H, Brandtzaeg P, Naess-Andresen CF, Dale I. (1997). Functional and clinical aspects of the myelomonocyte protein calprotectin. Molecular Pathology. 50 (3): 113-123. https://doi.org/10.1136/mp.50.3.113; PMid:9292145 PMCid:PMC379605
Josefsson S, Bunn SK, Domellöf M. (2007). Fecal Calprotectin in Very Low Birth Weight Infants. Journal of Pediatric Gastroenterology & Nutrition. 44 (4): 407-413. https://doi.org/10.1097/MPG.0b013e3180320643; PMid:17414135
Kliegman RM, Walsh MC. (1987). Neonatal necrotizing enterocolitis: Pathogenesis, classification, and spectrum of illness. Current Problems in Pediatrics. 17 (4): 219-288. https://doi.org/10.1016/0045-9380(87)90031-4; PMid:3556038
Legrand D. (2012). Lactoferrin, a key molecule in immune and inflammatory processes. Biochemistry and Cell Biology. 90 (3): 252-268. https://doi.org/10.1139/o11-056; PMid:22136726
Legrand D. (2016). Overview of Lactoferrin as a Natural Immune Modulator. The Journal of Pediatrics. 173: S10-S15. https://doi.org/10.1016/j.jpeds.2016.02.071; PMid:27234406
Liao Y, Jiang R, Lönnerdal B. (2012). Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life. Biochemistry and Cell Biology. 90 (3): 476-484. https://doi.org/10.1139/o11-075; PMid:22332905
MacQueen BC, Christensen RD, Yost CC, Gordon PV, Baer VL, Schlaberg R, Lowe J. (2018). Reference intervals for stool calprotectin in preterm neonates and their utility for the diagnosis of necrotizing enterocolitis. Journal of Perinatology. 38 (10): 1379-1385. https://doi.org/10.1038/s41372-018-0108-9; PMid:29740189
Mara MA, Good M, Weitkamp J-H. (2018). Innate and adaptive immunity in necrotizing enterocolitis. Seminars in Fetal and Neonatal Medicine. 23 (6): 394-399. https://doi.org/10.1016/j.siny.2018.08.002; PMid:30146477 PMCid:PMC6269198
Milton R, Gillespie D, Dyer C, Taiyari K, Carvalho MJ, Thomson K et al. (2022). Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study. The Lancet Global Health. 10 (5): e661-e672. https://doi.org/10.1016/S2214-109X(22)00043-2; PMid:35427523
Niño DF, Sodhi CP, Hackam DJ. (2016). Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nature Reviews Gastroenterology & Hepatology. 13 (10): 590-600. https://doi.org/10.1038/nrgastro.2016.119; PMid:27534694 PMCid:PMC5124124
Pirr S, Dauter L, Vogl T, Ulas T, Bohnhorst B, Roth J, Viemann D. (2021). S100A8/A9 is the first predictive marker for neonatal sepsis. Clinical and Translational Medicine. 11(4): https://doi.org/10.1002/ctm2.338; PMid:33931974 PMCid:PMC8021540
Rougé C, Butel M-J, Piloquet H, Ferraris L, Legrand A, Vodovar M et al. (2010). Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period. PLoS ONE. 5 (6): e11083. https://doi.org/10.1371/journal.pone.0011083; PMid:20552029 PMCid:PMC2884033
Savino F, Castagno E, Calabrese R, Viola S, Oggero R, Miniero R. (2010). High Faecal Calprotectin Levels in Healthy. Exclusively Breast-Fed Infants: 299-304. https://doi.org/10.1159/000255161; PMid:19887860
Terrin G, Passariello A, Manguso F, Salvia G, Rapacciuolo L, Messina F, Raimondi F, Canani RB. (2011). Serum Calprotectin: An Antimicrobial Peptide as a New Marker For the Diagnosis of Sepsis in Very Low Birth Weight Newborns. Clinical and Developmental Immunology. 2011: 1-6. https://doi.org/10.1155/2011/291085; PMid:21765851 PMCid:PMC3135082
Thibault M-P, Tremblay É, Horth C, Fournier-Morin A, Grynspan D, Babakissa C et al. (2022). Lipocalin-2 and calprotectin as stool biomarkers for predicting necrotizing enterocolitis in premature neonates. Pediatric Research. 91 (1): 129-136. https://doi.org/10.1038/s41390-021-01680-7; PMid:34465872 PMCid:PMC8770124
Tirone C, Pezza L, Paladini A, Tana M, Aurilia C, Lio A et al. (2019). Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes. Frontiers in Immunology: 10. https://doi.org/10.3389/fimmu.2019.02910; PMid:31921169 PMCid:PMC6920179
Ullah O, Khan A, Ambreen A, Ahmad I, Akhtar T, Gandapor AJ, Khan AM. (2016). Antibiotic Sensitivity pattern of Bacterial Isolates of Neonatal Septicemia in Peshawar, Pakistan. Archives of Iranian Medicine. 19 (12): 866-869. https://doi.org/0161912/AIM.009.
Van Zoonen AGJF, Hulzebos CV, Muller Kobold AC, Kooi EMW, Bos AF, Hulscher JBF. (2019). Serial fecal calprotectin in the prediction of necrotizing enterocolitis in preterm neonates. Journal of Pediatric Surgery. 54 (3): 455-459. https://doi.org/10.1016/j.jpedsurg.2018.04.034; PMid:29859621
Wang B, Timilsena YP, Blanch E, Adhikari B. (2019). Lactoferrin: Structure, function, denaturation and digestion. Critical Reviews in Food Science and Nutrition. 59 (4): 580-596. https://doi.org/10.1080/10408398.2017.1381583; PMid:28933602
Yoon JM, Park JY, Ko KO, Lim JW, Cheon EJ, Kim HJ. (2014). Fecal calprotectin concentration in neonatal necrotizing enterocolitis. Korean Journal of Pediatrics. 57 (8): 351-356. https://doi.org/10.3345/kjp.2014.57.8.351; PMid:25210522 PMCid:PMC4155179
Yui S, Nakatani Y, Mikami M. (2003). Calprotectin (S100A8/S100A9), an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity. Biological and Pharmaceutical Bulletin. 26 (6): 753-760. https://doi.org/10.1248/bpb.26.753; PMid:12808281
Zhang M, Zhang X, Zhang J. (2016). Diagnostic Value of Fecal Calprotectin in Preterm Infants with Necrotizing Enterocolitis. Clinical Laboratory, 62(05/2016). https://doi.org/10.7754/Clin.Lab.2015.150906
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Modern pediatrics. Ukraine
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “MODERN PEDIATRICS. UKRAINE” is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal “MODERN PEDIATRICS. UKRAINE” when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.
