Maria Carolina de Campos Martins¹, Daniela MLM Ferreira¹*, Larissa Prado Maia², Patrícia Terra Alves², Aline Teodoro de Paula², Fernanda M Santiago³, José R Mineo³, Mônica C Sopelete³, Francisco E Martinez⁴, Morun Bernardino Neto⁵, Luiz Ricardo Goulart² and Vânia OS Abdallah¹

¹Division of Neonatology, Department of Pediatrics, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil

*Corresponding Author: Daniela MLM Ferreira, Division of Neonatology, Department of Pediatrics, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.

Received: July 29, 2021; Published: November 26, 2021

Abstract

Objective: Infections are the main causes of morbidity and mortality in very low birth weight preterm neonates (VLBW PTN) leading to systemic inflammatory imbalance. The oropharyngeal administration of own mother's milk, particularly colostrum, has been suggested as an immunostimulatory action for protection against neonatal sepsis. As urine has been poorly evaluated in both systemic inflammation and neonatal sepsis, our purpose was to evaluate the effect of oropharyngeal administration of colostrum on the secretion of proinflammatory and anti-inflammatory cytokines in the urine of VLBW PTN.

Methods: From a randomized, double blinded, placebo-controlled trial, urine samples were randomly selected from 55 preterm infants, of which 29 underwent oropharyngeal administration of own mother's colostrum and 26 received distilled water. Urine samples were collected before and 24 hours after the end of the oropharyngeal administration and analyzed using the Milliplex-27 kit on the MagPix (Luminex) equipment.

Results: A significant reduction in proinflammatory cytokines like IFN - γ (p = 0.005), TNF - α (p = 0.002), IL - 8 (p = 0.012), IL - 9 (p = 0.011), IL -15 (p = 0.012), IL - 17a (p = 0.001) and RANTES (p = 0.018) was observed in the group of children undergoing oropharyngeal administration of colostrum. However, there was no statistically significant difference in the incidence of clinical (OR 1.023; CI 95% 0.344-3.040) and confirmed sepsis (OR 1.158; CI 95% 0.344-3.899) in very low birth weight preterm neonates undergoing oropharyngeal administration of colostrum when compared to the group receiving distilled water.

Conclusion The oropharyngeal administration of colostrum promoted an anti-inflammatory state, characterized by the reduction of proinflammatory cytokines, which may contribute to the reduction of the incidence of neonatal sepsis.

Keywords: Colostrum; Oropharyngeal Administration; Immune Therapy; Neonatal Sepsis; Premature Infant; Biomarkers

References

1. Camacho-Gonzalez A., et al. “Neonatal infectious diseases: evaluation of neonatal sepsis”. Pediatric Clinics of North America 2 (2013): 367-389.
2. Mussap M., et al. “The importance of biomarkers in neonatology”. Seminars in Fetal and Neonatal Medicine1 (2013): 56-64.
3. Bhandari V. “Effective Biomarkers for Diagnosis of Neonatal Sepsis”. Journal of the Paediatric Infectious Diseases Society 3 (2014): 234-245.
4. Sugitharini V., et al. “Inflammatory mediators of systemic inflammation in neonatal sepsis”. Inflammation Research 12 (2013): 1025-1034.
5. Machado JR., et al. “Neonatal sepsis and inflammatory mediators”. Mediators of Inflammation 2014 (2014): 269681.
6. Rodriguez NA., et al. “Oropharyngeal administration of colostrum to extremely low birth weight infants: theoretical perspectives”. Journal of Perinatology 1 (2009): 1-7.
7. Gephart SM and Weller M. “Colostrum as oral immune therapy to promote neonatal health”. Advance in Neonatal Care 1 (2014): 44-51.
8. Panchal H., et al. “Oropharyngeal colostrum for preterm infants: a systematic review and meta-analysis”. Advances in Nutrition 6 (2019): 1152-1162.
9. Sharma D., et al. “Role of Oropharyngeal Administration of Colostrum in Very Low Birth Weight Infants for Reducing Necrotizing Enterocolitis: A Randomized Controlled Trial”. American Journal of Perinatology 07 (2020): 716-721.
10. Tao J., et al. “Effects of oropharyngeal administration of colostrum on the incidence of necrotizing enterocolitis, late-onset sepsis, and death in preterm infants: a meta-analysis of RCTs”. European Journal of Clinical Nutrition 8 (2020): 1122-1131.
11. Lee J., et al. “Oropharyngeal colostrum administration in extremely premature infants: an RCT”. Paediatrics2 (2015): e357-366.
12. Lewis ED., et al. “The Importance of Human Milk for Immunity in Preterm Infants”. Clinics in Perinatology1 (2017): 23-47.
13. Rodriguez NA and Caplan MS. “Oropharyngeal administration of mother's milk to prevent necrotizing enterocolitis in extremely low-birth-weight infants: theoretical perspectives”. Journal of Perinatal and Neonatal Nursing 1 (2015): 81-90.
14. Ferreira DM., et al. “Randomized controlled trial of oropharyngeal colostrum administration in very-low-birth-weight preterm infants”. Journal of Paediatric Gastroenterology and Nutrition 1 (2019): 126-130.
15. Rodriguez NA., et al. “A pilot study to determine the safety and feasibility of oropharyngeal administration of own mother's colostrum to extremely low-birth-weight infants”. Advances in Neonatal Care 4 (2010): 206-212.
16. Andreas NJ., et al. “Human breast milk: A review on its composition and bioactivity”. Early Human Development 11 (2015): 629-635.
17. Garofalo R. “Cytokines in human milk”. The Journal of Paediatrics2 (2010): S36-40.
18. Rodriguez NA., et al. “Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial”. Trials 16 (2015): 453.
19. Levy O. “Innate immunity of the newborn: basic mechanisms and clinical correlates”. Nature Reviews Immunology5 (2007): 379-390.
20. Ludwig KR and Hummon AB. “Mass spectrometry for the discovery of biomarkers of sepsis”. Molecular Biosystems4 (2017): 648-664.
21. Bhatia J. “Human milk and the premature infant”. Annals of Nutrition and Metabolism3 (2013): 8-14.
22. Fattah MA., et al. “Utility of cytokine, adhesion molecule and acute phase proteins in early diagnosis of neonatal sepsis”. Journal of Natural Science, Biology, and Medicine1 (2017): 32-39.
23. Ng PC., et al. “The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis. Archives of Disease in Childhood”. Fetal and Neonatal Edition 5 (2015): F448-452.
24. Ballard O and Morrow AL. “Human milk composition: nutrients and bioactive factors”. Paediatric Clinics of North America1 (2013): 49-74.
25. Seigel JK., et al. “Early administration of oropharyngeal colostrum to extremely low birth weight infants”. Breastfeeding Medicine6 (2013): 491-495.
26. Gilfillan M and Bhandari V. “Biomarkers for the diagnosis of neonatal sepsis and necrotizing enterocolitis: Clinical practice guidelines”. Early Human Development 105 (2017): 25-33.
27. Martín-Álvarez E., et al. “Oropharyngeal colostrum positively modulates the inflammatory response in preterm neonates”. Nutrients2 (2020): 413.
28. Ye Q., et al. “Utility of cytokines to predict neonatal sepsis”. Paediatric Research4 (2017): 616-621.
29. Trend S., et al. “Levels of innate immune factors in preterm and term mothers' breast milk during the 1st month postpartum”. British Journal of Nutrition7 (2016): 1178-1193.
30. Barrera GJ and Sanchez G. “Cytokine modulation (IL-6, IL-8, IL-10) by human breast milk lipids on intestinal epithelial cells (Caco-2)”. The Journal of Maternal-Fetal and Neonatal Medicine15 (2016): 2505-2512.
31. Segura-Cervantes E., et al. “Inflammatory Response in Preterm and Very Preterm New-borns with Sepsis”. Mediators of Inflammation 2016 (2016): 6740827.
32. Nguyen DN., et al. “Transforming growth factor-beta2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine”. Journal of Physiology-Gastrointestinal and Liver Physiology7 (2014): G689-699.
33. Zhou M., et al. “Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis”. PLoS One5 (2015): e0127170.
34. Stojewska M., et al. “Evaluation of serum chemokine RANTES concentration as a biomarker in the diagnosis of early-onset severe infections in neonates”. Postepy Higieny I Medycyny Doswiadczalnej 70 (2016): 272-279.
35. Akdis M., et al. “Interleukins (from IL-1 to IL-38), interferons, transforming growth factor beta, and TNF-alpha: Receptors, functions, and roles in diseases”. The Journal of Allergy and Clinical Immunology4 (2016): 984-1010.
36. Akdis M., et al. “Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases”. The Journal of Allergy and Clinical Immunology 127.3 (2011): 701-721.
37. Cross AS. “IL-18/IL-1/IL-17A axis: A novel therapeutic target for neonatal sepsis?” Cytokine 86 (2016): 1-3.
38. Pynn JM., et al. “Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis”. Paediatric Research1 (2015): 76-81.
39. Sylvester KG., et al. “Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants”. The Journal of Paediatrics3 (2014): 607-612.
40. Suguna Narasimhulu S., et al. “Usefulness of urinary immune biomarkers in the evaluation of neonatal sepsis: a pilot project”. Clinical Paediatrics (Phila) 52.6 (2013): 520-526.

Citation

Citation: Daniela MLM Ferreira., et al. “Oropharyngeal Colostrum Administration and Anti-inflammatory Effects in Very Low Birth Weight Preterm Neonates". Acta Scientific Paediatrics 4.12 (2021): 39-47.

Copyright

Copyright: © 2021 Daniela MLM Ferreira., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.