ORIGINAL ARTICLE Buccal administration of human colostrum: impact on the oral microbiota of premature infants K Sohn 1 , KM Kalanetra 2 , DA Mills 2 and MA Underwood 1 OBJECTIVE: To determine whether the administration of mother’s colostrum into the buccal pouch in the first days of life alters the oral microbiota compared with control infants. STUDY DESIGN: In this pilot study, 12 very low birth weight (VLBW) infants were randomly assigned to receive either colostrum from their mothers directly into the buccal pouch every 2 h for 46 h or standard care. We analyzed the oral microbiota at initiation and 48 and 96 h later using next-generation sequencing. RESULT: The oral microbiota changed markedly over the 96 h period in all babies. Patterns of colonization differed between groups with Planococcaceae, the dominant family at 48 and 96 h in the colostrum group, and Moraxellaceae and Staphylococcaceae, the dominant families at 48 and 96 h, respectively, in the control group. CONCLUSION: Buccal administration of mother’s colostrum to VLBW infants influenced the colonization of the oral cavity with differences persisting 48 h after completion of the intervention. Journal of Perinatology (2016) 36, 106–111; doi:10.1038/jp.2015.157; published online 10 December 2015 INTRODUCTION Human colostrum contains cytokines, antimicrobial peptides and proteins, hormones, cellular immune components and other biological substances that have immunomodulatory effects upon lymphoid tissues. 1–3 These benefits may be especially important for very low birth weight (VLBW) infants, who are at greatly increased risk for infection due to prematurity. Ingested colostrum shapes the gut microbiota, decreases the risk of necrotizing enterocolitis 4,5 and provides protective anti-inflammatory molecules with the potential to blunt the often exuberant inflammatory response of premature infants. 6 However, many small premature infants are not fed for several days after birth. Administration of small volumes of colostrum directly into the buccal cavity of intubated premature infants has been shown to be feasible and safe. 7,8 One study suggested that buccal colostrum may be nutritionally beneficial leading to improved growth, 8 while another demonstrated a decreased risk of clinical sepsis (though this study was not powered to examine sepsis as an outcome). 9 Additional theoretical benefits of buccal colostrum include stimulation of the oropharyngeal-associated lymphatic tissues, 10 decreased risk of ventilator-associated pneumonia 11 and altera- tion of the oral microbiota. Several neonatal intensive care units have adopted this practice 12 although evidence for benefit is limited. Oral swabbing with chlorhexidine has been shown to decrease the risk of ventilator-associated pneumonia in adult intensive care unit patients. 13 A recent retrospective cohort study of mechanically ventilated VLBW infants found oral care with mother’s own milk (colostrum, transitional milk and mature milk) was feasible and safe, however there were no differences in health outcomes (rate of positive tracheal aspirates, positive blood cultures, the number of ventilator days and length of stay) between the 68 infants receiving the intervention and the 70 infants that did not. 14 The largest retrospective cohort study to date, comparing 89 premature infants who received ‘oropharyngeal’ colostrum and 280 premature infants who did not, demonstrated no differences in the incidence of necrotizing enterocolitis or nosocomial infection. 8 To date, there is no evidence that oral care with colostrum alters the oral microbiota or decreases the risk of ventilator-associated pneumonia in premature infants. We sought to add to the literature by conducting a pilot study of the impact of colostrum on the composition of the oral microbiota in premature infants. METHODS Study design We conducted a randomized controlled clinical trial from November 2013 to October 2014 in the neonatal intensive care unit of the University of California Davis Children’s Hospital in Sacramento, California. The University Institutional Review Board reviewed and approved the protocol. The trial was registered at clinicaltrials.gov (NCT02306980). For this pilot study, a sample size of 12 patients was chosen based on feasibility of completion with recognition that such a study is only powered to demonstrate large differences in the primary outcome but is useful for the generation of preliminary data to more accurately justify a larger study. For example, assuming alpha 0.05 a sample size of six in each group could identify a change in the percentage of a single bacterial taxon from 95 to 8% with power 0.80. Participants Neonates were screened upon admission to the neonatal intensive care unit to determine eligibility. Inclusion criteria included birth weight o1500 g, age o7 days, intubation within 48 h of birth and availability of maternal colostrum. Neonates with a lethal medical condition were excluded. One of two investigators met with parents of eligible infants in person to inform them of the purpose of the study, describe the intervention and explain possible benefits and risks. Their questions were answered and additional meetings were arranged as needed to answer 1 Division of Neonatology, Department of Pediatrics, University of California Davis, Sacramento, CA, USA and 2 Department of Food Science and Technology, University of California Davis, Davis, CA, USA. Correspondence: Dr MA Underwood, Division of Neonatology, Department of Pediatrics, University of California Davis, 2516 Stockton Boulevard, Sacramento, CA 95817, USA. E-mail: munderwood@ucdavis.edu Received 22 July 2015; revised 12 September 2015; accepted 21 September 2015; published online 10 December 2015 Journal of Perinatology (2016) 36, 106 – 111 © 2016 Nature America, Inc. All rights reserved 0743-8346/16 www.nature.com/jp