Abstract
Ventilator-associated pneumonia (VAP) is a frequent nosocomial infection in neonatal intensive care units (NICU). Extremely preterm infants are at highest risk of developing VAP. Several studies indicate that oral care included in a preventive protocol effectively reduces neonatal VAP incidence. We investigated the effects of oral care with breast milk on oral immune defenses and microbiota in extremely preterm infants. Thirty infants born ≤ 30 weeks gestation hospitalized at our NICU were selected and divided into three groups: oral care with breast milk, formula, or sterile water. Effects on oral immune defenses in vivo were studied using ELISA to measure lactoferrin (LF) and secretory immunoglobulin A (sIgA) in pharyngeal aspirates before and after oral care. Different LF concentrations were tested in vitro to assess their effects on loads of selected bacterial species by culture. Effects on selected bacteria potentially responsible for VAP in vivo were studied by real-time PCR detection in pharyngeal aspirates before and after oral care. Oral care with breast milk significantly increases LF concentrations to 69.8 × 103 ng/ml (p = 0.012) and sIgA to 36.8 × 103 ng/ml (p = 0.017) in vivo. These LF concentrations considerably reduce loads of E. coli, S. epidermidis, S. aureus, and P. aeruginosa, in vitro. However, contrary to our expectation, no effect on colonization of bacteria most commonly responsible for VAP was found in vivo.
Conclusion: In extremely preterm infants, oral care with breast milk increases local immune defense markers (LF, sIgA), which combat bacterial infections. Further clinical trials should be conducted to evaluate their effects on VAP prevention in neonates.
What is Known: • The population at higher risk to develop VAP are preterm infants. • Several studies indicate oral care within a preventive bundle is effective in reducing neonatal VAP incidence. What is New: • In extremely premature infants, oral care with breast milk causes a significant increase in local immune defences in terms of lactoferrin (LF) and secretory immunoglobulin A (sIgA). • LF concentrations obtained after oral care with breast milk decreased loads of bacteria most commonly responsible for VAP in premature infants under experimental in-vitro. |
Similar content being viewed by others
Abbreviations
- LF::
-
Lactoferrin
- NICU::
-
Neonatal intensive care unit
- PCR::
-
Polymerase chain reaction
- sIgA::
-
Secretory immunoglobulin A
- VAP::
-
Ventilator-associated pneumonia
References
Cernada M, Brugada M, Golombek S, Vento M (2014) Ventilator-associated pneumonia in neonatal patients: an update. Neonatology 105:98–107. https://doi.org/10.1159/000355539
Dell’Orto V, Raschetti R, Centorrino R et al (2019) Short- and long-term respiratory outcomes in neonates with ventilator-associated pneumonia. Pediatr Pulmonol 54:1982–1988. https://doi.org/10.1002/ppul.24487
Cernada M, Aguar M, Brugada M et al (2013) Ventilator-associated pneumonia in newborn infants diagnosed with an invasive bronchoalveolar lavage technique: a prospective observational study. Pediatr Crit Care Med 14:55–61. https://doi.org/10.1097/PCC.0b013e318253ca31
Zhao T, Wu X, Zhang Q, et al (2020) Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev 12:CD008367. https://doi.org/10.1002/14651858.CD008367.pub4
Ponnusamy V, Venkatesh V, Clarke P (2014) Skin antisepsis in the neonate: what should we use? Curr Opin Infect Dis 27:244–250. https://doi.org/10.1097/QCO.0000000000000064
Pinilla-González A, Solaz-García Á, Parra-Llorca A et al (2021) Preventive bundle approach decreases the incidence of ventilator-associated pneumonia in newborn infants. J Perinatol 41:1467–1473. https://doi.org/10.1038/s41372-021-01086-7
Chen L-L, Liu J, Mu X-H et al (2022) Oropharyngeal administration of mother’s own milk influences levels of salivary sIgA in preterm infants fed by gastric tube. Sci Rep 12:2233. https://doi.org/10.1038/s41598-022-06243-2
Manzoni P, Rinaldi M, Cattani S et al (2009) Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 302:1421–1428. https://doi.org/10.1001/jama.2009.1403
Woof JM, Kerr MA (2006) The function of immunoglobulin A in immunity. J Pathol 208:270–282. https://doi.org/10.1002/path.1877
Rodriguez NA, Meier PP, Groer MW et al (2010) A pilot study to determine the safety and feasibility of oropharyngeal administration of own mother’s colostrum to extremely low-birth-weight infants. Adv Neonatal Care 10:206–212. https://doi.org/10.1097/ANC.0b013e3181e94133
Lee J, Kim H-S, Jung YH et al (2015) Oropharyngeal colostrum administration in extremely premature infants: an RCT. Pediatrics 135:e357-366. https://doi.org/10.1542/peds.2014-2004
Picaud J-C, Buffin R (2017) Human milk—treatment and quality of banked human milk. Clin Perinatol 44:95–119. https://doi.org/10.1016/j.clp.2016.11.003
Foglia EE, Ades A, Sawyer T et al (2019) Neonatal intubation practice and outcomes: an international registry study. Pediatrics 143:e20180902. https://doi.org/10.1542/peds.2018-0902
Dell’Orto V, Bourgeois-Nicolaos N, Rouard C et al (2018) Cell count analysis from nonbronchoscopic bronchoalveolar lavage in preterm infants. J Pediatr 200:30-37.e2. https://doi.org/10.1016/j.jpeds.2018.04.074
Agence Nationale de Sécurité du Médicament et des Produits de Santé (2020) Bonnes pratiques des lactariums [Good Human milk bank Practice]. https://ansm.sante.fr/documents/reference/bonnes-pratiques-des-lactariums. Accessed 25 Oct 2021
Rigourd V, Dridi Brahim I, Smii S et al (2017) Guidelines for multivitamin administration in fortified human milk prepared for preterm infants. Arch Pediatr 24:107–111. https://doi.org/10.1016/j.arcped.2016.11.003
Mohan R, Koebnick C, Schildt J et al (2008) Effects of Bifidobacterium lactis Bb12 supplementation on body weight, fecal pH, acetate, lactate, calprotectin, and IgA in preterm infants. Pediatr Res 64:418–422. https://doi.org/10.1203/PDR.0b013e318181b7fa
Hofman L, Le T (2002) Preliminary pediatric reference range for secretory IgA in saliva using an enzyme immunoassay Clin Chem 48: Suppl A169–70
Perea L, Cantó E, Suarez-Cuartin G et al (2021) A cluster analysis of bronchiectasis patients based on the airway immune profile. Chest 159:1758–1767. https://doi.org/10.1016/j.chest.2020.11.011
Ochoa TJ, Zegarra J, Bellomo S et al (2020) Randomized controlled trial of bovine lactoferrin for prevention of sepsis and neurodevelopment impairment in infants weighing less than 2000 grams. J Pediatr 219:118-125.e5. https://doi.org/10.1016/j.jpeds.2019.12.038
Rivas Caldas R, Le Gall F, Revert K et al (2015) Pseudomonas aeruginosa and periodontal pathogens in the oral cavity and lungs of cystic fibrosis patients: a case-control study. J Clin Microbiol 53:1898–1907. https://doi.org/10.1128/JCM.00368-15
Nakagawa S, Taneike I, Mimura D et al (2005) Gene sequences and specific detection for Panton-Valentine leukocidin. Biochem Biophys Res Commun 328:995–1002. https://doi.org/10.1016/j.bbrc.2005.01.054
Lepainteur M, Desroches M, Bourrel AS et al (2013) Role of the central venous catheter in bloodstream infections caused by coagulase-negative staphylococci in very preterm neonates. Pediatr Infect Dis J 32:622–628. https://doi.org/10.1097/INF.0b013e318289de0f
Stefanescu BM, Hétu C, Slaughter JC et al (2013) A pilot study of Biotene OralBalance® gel for oral care in mechanically ventilated preterm neonates. Contemp Clin Trials 35:33–39. https://doi.org/10.1016/j.cct.2013.03.010
Chirico G, Marzollo R, Cortinovis S et al (2008) Antiinfective properties of human milk. J Nutr 138:1801S-1806S. https://doi.org/10.1093/jn/138.9.1801S
Katayama Y, Takanishi H, Sato Y et al (2021) Effect of oral care in reducing the incidence of early-onset ventilator-associated pneumonia in preterm infants. Pediatr Pulmonol 56:2570–2575. https://doi.org/10.1002/ppul.25451
Manzoni P, De Luca D, Stronati M et al (2013) Prevention of nosocomial infections in neonatal intensive care units. Am J Perinatol 30:81–88. https://doi.org/10.1055/s-0032-1333131
Miller J, Tonkin E, Damarell RA et al (2018) A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients 10:E707. https://doi.org/10.3390/nu10060707
Acknowledgements
The authors are grateful to NICU nurses who actively participated in the study. We also thank Peggy Hanemann-Castex for English editing.
Funding
This work was supported by AP-HP Université Paris-Saclay.
Author information
Authors and Affiliations
Contributions
DDL and FDP conceived, designed, and supervised the study. DDL, FDP, and NBN wrote the manuscript. NBN, AR, and ES performed and analyzed data from studies. DDL and SA performed the clinical study and statistical analyses. All authors contributed to the critical review of the manuscript.
Corresponding author
Ethics declarations
Ethics approval
This study protocol was reviewed and approved by CPP Ile de France VII Hôpital Bicêtre France), approval number (CPP-RCB: 2015-A00115-44).
Consent to participate
Parents or guardians gave written informed consent prior to the enrolment.
Competing interests
The authors declare no competing interests.
Additional information
Communicated by Peter de Winter
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Bourgeois-Nicolaos, N., Raynor, A., Shankar-Aguilera, S. et al. Breast milk in neonate oral care: oropharyngeal effects in extremely preterm infants. Eur J Pediatr 182, 385–392 (2023). https://doi.org/10.1007/s00431-022-04692-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-022-04692-5