The Microbiota of the Extremely Preterm Infant

Mark A Underwood, Kristin Sohn, Mark A Underwood, Kristin Sohn

Abstract

Colonization of the extremely preterm infant's gastrointestinal tract and skin begins in utero and is influenced by a variety of factors, the most important including gestational age and environmental exposures. The composition of the intestinal and skin microbiota influences the developing innate and adaptive immune responses with short-term and long-term consequences including altered risks for developing necrotizing enterocolitis, sepsis, and a wide variety of microbe-related diseases of children and adults. Alteration of the composition of the microbiota to decrease disease risk is particularly appealing for this ultra-high-risk cohort that is brand new from an evolutionary standpoint.

Keywords: Dysbiosis; Intestinal tract; Late-onset sepsis; Microbiota; Necrotizing enterocolitis; Oral cavity; Skin.

Copyright © 2017 Elsevier Inc. All rights reserved.

References

    1. Vatanen T., Kostic A.D., d'Hennezel E. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell. 2016;165(4):842–853.
    1. Taira R., Yamaguchi S., Shimizu K. Bacterial cell wall components regulate adipokine secretion from visceral adipocytes. J Clin Biochem Nutr. 2015;56(2):149–154.
    1. Cani P.D., Plovier H., Van Hul M. Endocannabinoids–at the crossroads between the gut microbiota and host metabolism. Nature reviews. Endocrinology. 2016;12(3):133–143.
    1. LaTuga M.S., Ellis J.C., Cotton C.M. Beyond bacteria: a study of the enteric microbial consortium in extremely low birth weight infants. PLoS One. 2011;6(12):e27858.
    1. Wassenaar T.M., Panigrahi P. Is a foetus developing in a sterile environment? Lett Appl Microbiol. 2014;59(6):572–579.
    1. Boggess K.A., Society for Maternal-Fetal Medicine Publications Committee Maternal oral health in pregnancy. Obstet Gynecol. 2008;111(4):976–986.
    1. Buduneli N., Baylas H., Buduneli E. Periodontal infections and pre-term low birth weight: a case-control study. J Clin Periodontol. 2005;32(2):174–181.
    1. Lopez N.J., Smith P.C., Gutierrez J. Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: a randomized controlled trial. J Periodontol. 2002;73(8):911–924.
    1. Ercan E., Eratalay K., Deren O. Evaluation of periodontal pathogens in amniotic fluid and the role of periodontal disease in pre-term birth and low birth weight. Acta Odontol Scand. 2013;71(3–4):553–559.
    1. Han Y.W., Shen T., Chung P. Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol. 2009;47(1):38–47.
    1. Ao M., Miyauchi M., Furusho H. Dental infection of Porphyromonas gingivalis induces preterm birth in mice. PLoS One. 2015;10(8):e0137249.
    1. Collado M.C., Rautava S., Aakko J. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016;6:23129.
    1. Olomu I.N., Hecht J.L., Onderdonk A.O., Extremely low gestational age newborn study I Perinatal correlates of Ureaplasma urealyticum in placenta parenchyma of singleton pregnancies that end before 28 weeks of gestation. Pediatrics. 2009;123(5):1329–1336.
    1. Sweeney E.L., Kallapur S.G., Gisslen T. Placental infection with Ureaplasma species is associated with histologic chorioamnionitis and adverse outcomes in moderately preterm and late-preterm infants. J Infect Dis. 2016;213(8):1340–1347.
    1. Dominguez-Bello M.G., Costello E.K., Contreras M. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–11975.
    1. Costello E.K., Carlisle E.M., Bik E.M. Microbiome assembly across multiple body sites in low-birthweight infants. MBio. 2013;4(6):e00782-13.
    1. Moles L., Gomez M., Heilig H. Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One. 2013;8(6):e66986.
    1. Schwiertz A., Gruhl B., Lobnitz M. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res. 2003;54(3):393–399.
    1. La Rosa P.S., Warner B.B., Zhou Y. Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci U S A. 2014;111(34):12522–12527.
    1. Ferraris L., Butel M.J., Campeotto F. Clostridia in premature neonates' gut: incidence, antibiotic susceptibility, and perinatal determinants influencing colonization. PLoS One. 2012;7(1):e30594.
    1. Warner B.B., Tarr P.I. Necrotizing enterocolitis and preterm infant gut bacteria. Semin Fetal Neonatal Med. 2016;21(6):394–399.
    1. Warner B.B., Deych E., Zhou Y. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2016;387(10031):1928–1936.
    1. Patel K., Konduru K., Patra A.K. Trends and determinants of gastric bacterial colonization of preterm neonates in a NICU setting. PLoS One. 2015;10(7):e0114664.
    1. Milisavljevic V., Garg M., Vuletic I. Prospective assessment of the gastroesophageal microbiome in VLBW neonates. BMC Pediatr. 2013;13:49.
    1. Shimizu A., Shimizu K., Nakamura T. Non-pathogenic bacterial flora may inhibit colonization by methicillin-resistant Staphylococcus aureus in extremely low birth weight infants. Neonatology. 2008;93(3):158–161.
    1. Makhoul I.R., Sujov P., Ardekian L. Factors influencing oral colonization in premature infants. Isr Med Assoc J. 2002;4(2):98–102.
    1. Sohn K., Kalanetra K.M., Mills D.A. Buccal administration of human colostrum: impact on the oral microbiota of premature infants. J Perinatol. 2016;36(2):106–111.
    1. Visscher M.O., Adam R., Brink S. Newborn infant skin: physiology, development, and care. Clin Dermatol. 2015;33(3):271–280.
    1. Evans N.J., Rutter N. Development of the epidermis in the newborn. Biol Neonate. 1986;49(2):74–80.
    1. Erdemir A., Kahramaner Z., Yuksel Y. The effect of topical ointment on neonatal sepsis in preterm infants. J Matern Fetal Neonatal Med. 2015;28(1):33–36.
    1. Choi Y., Saha S.K., Ahmed A.S. Routine skin cultures in predicting sepsis pathogens among hospitalized preterm neonates in Bangladesh. Neonatology. 2008;94(2):123–131.
    1. Huang Y.C., Chou Y.H., Su L.H. Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units. Pediatrics. 2006;118(2):469–474.
    1. Hartz L.E., Bradshaw W., Brandon D.H. Potential NICU environmental influences on the neonate's microbiome: a systematic review. Adv Neonatal Care. 2015;15(5):324–335.
    1. Yee W.H., Soraisham A.S., Shah V.S. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics. 2012;129(2):e298–e304.
    1. Salzman N.H., Bevins C.L. Dysbiosis–a consequence of Paneth cell dysfunction. Semin Immunol. 2013;25(5):334–341.
    1. Heida F.H., Beyduz G., Bulthuis M.L. Paneth cells in the developing gut: when do they arise and when are they immune competent? Pediatr Res. 2016;80(2):306–310.
    1. McElroy S.J., Underwood M.A., Sherman M.P. Paneth cells and necrotizing enterocolitis: a novel hypothesis for disease pathogenesis. Neonatology. 2013;103(1):10–20.
    1. Wang Y., Hoenig J.D., Malin K.J. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J. 2009;3(8):944–954.
    1. Zhou Y., Shan G., Sodergren E. Longitudinal analysis of the premature infant intestinal microbiome prior to necrotizing enterocolitis: a case-control study. PLoS One. 2015;10(3):e0118632.
    1. Morrow A.L., Lagomarcino A.J., Schibler K.R. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants. Microbiome. 2013;1(1):13.
    1. Mai V., Young C.M., Ukhanova M. Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS One. 2011;6(6):e20647.
    1. Mshvildadze M., Neu J., Shuster J. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr. 2010;156(1):20–25.
    1. de la Cochetiere M.F., Piloquet H., des Robert C. Early intestinal bacterial colonization and necrotizing enterocolitis in premature infants: the putative role of Clostridium. Pediatr Res. 2004;56(3):366–370.
    1. Stewart C.J., Marrs E.C., Magorrian S. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr. 2012;101(11):1121–1127.
    1. Smith B., Bode S., Skov T.H. Investigation of the early intestinal microflora in premature infants with/without necrotizing enterocolitis using two different methods. Pediatr Res. 2012;71(1):115–120.
    1. Normann E., Fahlen A., Engstrand L. Intestinal microbial profiles in extremely preterm infants with and without necrotizing enterocolitis. Acta Paediatr. 2013;102(2):129–136.
    1. Torrazza R.M., Ukhanova M., Wang X. Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis. PLoS One. 2013;8(12):e83304.
    1. Jenke A.C., Postberg J., Mariel B. S100A12 and hBD2 correlate with the composition of the fecal microflora in ELBW infants and expansion of E. coli is associated with NEC. Biomed Res Int. 2013;2013:150372.
    1. McMurtry V.E., Gupta R.W., Tran L. Bacterial diversity and Clostridia abundance decrease with increasing severity of necrotizing enterocolitis. Microbiome. 2015;3:11.
    1. Sim K., Shaw A.G., Randell P. Dysbiosis anticipating necrotizing enterocolitis in very premature infants. Clin Infect Dis. 2015;60(3):389–397.
    1. Heida F.H., van Zoonen A.G., Hulscher J.B. A necrotizing enterocolitis-associated gut microbiota is present in the meconium: results of a prospective study. Clin Infect Dis. 2016;62(7):863–870.
    1. Ward D.V., Scholz M., Zolfo M. 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.
    1. Stewart C.J., Marrs E.C., Nelson A. Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis. PLoS One. 2013;8(8):e73465.
    1. Claud E.C., Keegan K.P., Brulc J.M. Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants. Microbiome. 2013;1(1):20.
    1. Egan C.E., Sodhi C.P., Good M. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest. 2016;126(2):495–508.
    1. Winter S.E., Baumler A.J. Dysbiosis in the inflamed intestine: chance favors the prepared microbe. Gut Microbes. 2014;5(1):71–73.
    1. Tarr P.I., Warner B.B. Gut bacteria and late-onset neonatal bloodstream infections in preterm infants. Semin Fetal Neonatal Med. 2016;21(6):388–393.
    1. Shaw A.G., Sim K., Randell P. Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants. PLoS One. 2015;10(7):e0132923.
    1. Taft D.H., Ambalavanan N., Schibler K.R. Center variation in intestinal microbiota prior to late-onset sepsis in preterm infants. PLoS One. 2015;10(6):e0130604.
    1. Carl M.A., Ndao I.M., Springman A.C. Sepsis from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections. Clin Infect Dis. 2014;58(9):1211–1218.
    1. Madan J.C., Salari R.C., Saxena D. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child. 2012;97(6):F456–F462.
    1. Ponnusamy V., Perperoglou A., Venkatesh V. Skin colonisation at the catheter exit site is strongly associated with catheter colonisation and catheter-related sepsis. Acta Paediatr. 2014;103(12):1233–1238.
    1. Garland J.S., Alex C.P., Johnston N. Association between tracheal pepsin, a reliable marker of gastric aspiration, and head of bed elevation among ventilated neonates. J Neonatal Perinatal Med. 2014;7(3):185–192.
    1. Oue S., Hiroi M., Ogawa S. Association of gastric fluid microbes at birth with severe bronchopulmonary dysplasia. Arch Dis Child. 2009;94(1):F17–F22.
    1. Young K.C., Del Moral T., Claure N. The association between early tracheal colonization and bronchopulmonary dysplasia. J Perinatol. 2005;25(6):403–407.
    1. Lohmann P., Luna R.A., Hollister E.B. The airway microbiome of intubated premature infants: characteristics and changes that predict the development of bronchopulmonary dysplasia. Pediatr Res. 2014;76(3):294–301.
    1. Mourani P.M., Harris J.K., Sontag M.K. Molecular identification of bacteria in tracheal aspirate fluid from mechanically ventilated preterm infants. PLoS One. 2011;6(10):e25959.
    1. Kembel S.W., Jones E., Kline J. Architectural design influences the diversity and structure of the built environment microbiome. ISME J. 2012;6(8):1469–1479.
    1. Hewitt K.M., Mannino F.L., Gonzalez A. Bacterial diversity in two neonatal intensive care units (NICUs) PLoS One. 2013;8(1):e54703.
    1. Bokulich N.A., Mills D.A., Underwood M.A. Surface microbes in the neonatal intensive care unit: changes with routine cleaning and over time. J Clin Microbiol. 2013;51(8):2617–2624.
    1. Homaira N., Sheils J., Stelzer-Braid S. Respiratory syncytial virus is present in the neonatal intensive care unit. J Med Virol. 2016;88(2):196–201.
    1. Davis R.J., Jensen S.O., Van Hal S. Whole genome sequencing in real-time investigation and management of a Pseudomonas aeruginosa outbreak on a neonatal intensive care unit. Infect Control Hosp Epidemiol. 2015;36(9):1058–1064.
    1. Paul L.M., Hegde A., Pai T. An outbreak of Burkholderia cepacia bacteremia in a neonatal intensive care unit. Indian J Pediatr. 2016;83(4):285–288.
    1. Decousser J.W., Ramarao N., Duport C. Bacillus cereus and severe intestinal infections in preterm neonates: putative role of pooled breast milk. Am J Infect Control. 2013;41(10):918–921.
    1. Nakamura K., Kaneko M., Abe Y. Outbreak of extended-spectrum beta-lactamase-producing Escherichia coli transmitted through breast milk sharing in a neonatal intensive care unit. J Hosp Infect. 2016;92(1):42–46.
    1. Salamat S., Fischer D., van der Linden M. Neonatal group B streptococcal septicemia transmitted by contaminated breast milk, proven by pulsed field gel electrophoresis in 2 cases. Pediatr Infect Dis J. 2014;33(4):428.
    1. Xu F., Li P., Ming X. Detection of Cronobacter species in powdered infant formula by probe-magnetic separation PCR. J Dairy Sci. 2014;97(10):6067–6075.
    1. van Acker J., de Smet F., Muyldermans G. Outbreak of necrotizing enterocolitis associated with Enterobacter sakazakii in powdered milk formula. J Clin Microbiol. 2001;39(1):293–297.
    1. Hutchinson J., Runge W., Mulvey M. Burkholderia cepacia infections associated with intrinsically contaminated ultrasound gel: the role of microbial degradation of parabens. Infect Control Hosp Epidemiol. 2004;25(4):291–296.
    1. Nannini E.C., Ponessa A., Muratori R. Polyclonal outbreak of bacteremia caused by Burkholderia cepacia complex and the presumptive role of ultrasound gel. Braz J Infect Dis. 2015;19(5):543–545.
    1. Morillo A., Gonzalez V., Aguayo J. A six-month Serratia marcescens outbreak in a neonatal intensive care unit. Enferm Infecc Microbiol Clin. 2016;34(10):645–651.
    1. Macdonald T.M., Langley J.M., Mailman T. Serratia marcescens outbreak in a neonatal intensive care unit related to the exit port of an oscillator. Pediatr Crit Care Med. 2011;12(6):e282–e286.
    1. Arslan U., Erayman I., Kirdar S. Serratia marcescens sepsis outbreak in a neonatal intensive care unit. Pediatr Int. 2010;52(2):208–212.
    1. Buffet-Bataillon S., Rabier V., Betremieux P. Outbreak of Serratia marcescens in a neonatal intensive care unit: contaminated unmedicated liquid soap and risk factors. J Hosp Infect. 2009;72(1):17–22.
    1. Madani T.A., Alsaedi S., James L. Serratia marcescens-contaminated baby shampoo causing an outbreak among newborns at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. J Hosp Infect. 2011;78(1):16–19.
    1. Underwood M.A., Kalanetra K.M., Bokulich N.A. Prebiotic oligosaccharides in premature infants. J Pediatr Gastroenterol Nutr. 2014;58(3):352–360.
    1. Underwood M.A., Gaerlan S., De Leoz M.L. Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res. 2015;78(6):670–677.
    1. Aceti A., Gori D., Barone G. Probiotics and time to achieve full enteral feeding in human milk-fed and formula-fed preterm infants: systematic review and meta-analysis. Nutrients. 2016;8(8):471.
    1. Rao S.C., Athalye-Jape G.K., Deshpande G.C. Probiotic supplementation and late-onset sepsis in preterm infants: a meta-analysis. Pediatrics. 2016;137(3):e20153684.
    1. Alfaleh K., Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2014;(4) CD005496.
    1. Olsen R., Greisen G., Schroder M. Prophylactic probiotics for preterm infants: a systematic review and meta-analysis of observational studies. Neonatology. 2016;109(2):105–112.
    1. Vongbhavit K., Underwood M.A. Prevention of necrotizing enterocolitis through manipulation of the intestinal microbiota of the premature infant. Clin Ther. 2016;38(4):716–732.
    1. Kanic Z., Micetic Turk D., Burja S. Influence of a combination of probiotics on bacterial infections in very low birthweight newborns. Wien Klin Wochenschr. 2015;127(Suppl 5):S210–S215.
    1. Xu L., Wang Y., Wang Y. A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants. J Pediatr (Rio J) 2016;92(3):296–301.
    1. Manzoni P., Meyer M., Stolfi I. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early Hum Dev. 2014;90(Suppl 1):S60–S65.
    1. Underwood M.A., Salzman N.H., Bennett S.H. A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations in preterm infants: impact on weight gain, intestinal microbiota, and fecal short-chain fatty acids. J Pediatr Gastroenterol Nutr. 2009;48(2):216–225.
    1. Saengtawesin V., Tangpolkaiwalsak R., Kanjanapattankul W. Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. J Med Assoc Thai. 2014;97(Suppl 6):S20–S25.
    1. Costeloe K., Hardy P., Juszczak E., Probiotics in Preterm Infants Study Collaborative Group Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet. 2016;387(10019):649–660.
    1. Van Niekerk E., Nel D.G., Blaauw R. Probiotics reduce necrotizing enterocolitis severity in HIV-exposed premature infants. J Trop Pediatr. 2015;61(3):155–164.
    1. Tewari V.V., Dubey S.K., Gupta G. Bacillus clausii for prevention of late-onset sepsis in preterm infants: a randomized controlled trial. J Trop Pediatr. 2015;61(5):377–385.
    1. Oncel M.Y., Sari F.N., Arayici S. Lactobacillus reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: a randomised controlled trial. Arch Dis Child. 2014;99(2):F110–F115.
    1. Patole S., Keil A.D., Chang A. Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates–a randomised double blind placebo controlled trial. PLoS One. 2014;9(3):e89511.
    1. Totsu S., Yamasaki C., Terahara M., Probiotics Study Group in Japan Bifidobacterium and enteral feeding in preterm infants: cluster-randomized trial. Pediatr Int. 2014;56(5):714–719.
    1. Jacobs S.E., Tobin J.M., Opie G.F. Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics. 2013;132(6):1055–1062.
    1. Al-Hosni M., Duenas M., Hawk M. Probiotics-supplemented feeding in extremely low-birth-weight infants. J Perinatol. 2012;32(4):253–259.
    1. Mihatsch W.A., Vossbeck S., Eikmanns B. Effect of Bifidobacterium lactis on the incidence of nosocomial infections in very-low-birth-weight infants: a randomized controlled trial. Neonatology. 2010;98(2):156–163.
    1. Rouge C., Piloquet H., Butel M.J. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2009;89(6):1828–1835.
    1. Lin H.C., Hsu C.H., Chen H.L. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics. 2008;122(4):693–700.
    1. Wang C., Shoji H., Sato H. Effects of oral administration of Bifidobacterium breve on fecal lactic acid and short-chain fatty acids in low birth weight infants. J Pediatr Gastroenterol Nutr. 2007;44(2):252–257.
    1. Bin-Nun A., Bromiker R., Wilschanski M. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. 2005;147(2):192–196.
    1. Guthmann F., Arlettaz Mieth R.P., Bucher H.U. Short courses of dual-strain probiotics appear to be effective in reducing necrotising enterocolitis. Acta Paediatr. 2016;105(3):255–259.
    1. Janvier A., Malo J., Barrington K.J. Cohort study of probiotics in a North American neonatal intensive care unit. J Pediatr. 2014;164(5):980–985.
    1. Hunter C., Dimaguila M.A., Gal P. Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis. BMC Pediatr. 2012;12:142.
    1. Luoto R., Matomaki J., Isolauri E. Incidence of necrotizing enterocolitis in very-low-birth-weight infants related to the use of Lactobacillus GG. Acta Paediatr. 2010;99(8):1135–1138.
    1. Bury R.G., Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Database Syst Rev. 2001;(1) CD000405.
    1. Strenger V., Gschliesser T., Grisold A. Orally administered colistin leads to colistin-resistant intestinal flora and fails to prevent faecal colonisation with extended-spectrum beta-lactamase-producing enterobacteria in hospitalised newborns. Int J Antimicrob Agents. 2011;37(1):67–69.
    1. Lee J., Kim H.S., Jung Y.H. Oropharyngeal colostrum administration in extremely premature infants: an RCT. Pediatrics. 2015;135(2):e357–e366.
    1. Rodriguez N.A., Vento M., Claud E.C. Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial. Trials. 2015;16:453.
    1. Dettenkofer M., Wenzler S., Amthor S. Does disinfection of environmental surfaces influence nosocomial infection rates? A systematic review. Am J Infect Control. 2004;32(2):84–89.
    1. Donskey C.J. Does improving surface cleaning and disinfection reduce health care-associated infections? Am J Infect Control. 2013;41(5 Suppl):S12–S19.
    1. Swan J.T., Ashton C.M., Bui L.N. Effect of chlorhexidine bathing every other day on prevention of hospital-acquired infections in the surgical ICU: a single-center, randomized controlled trial. Crit Care Med. 2016;44(10):1822–1832.
    1. Cleminson J., McGuire W. Topical emollient for preventing infection in preterm infants. Cochrane Database Syst Rev. 2016;(1) CD001150.
    1. Pabst R.C., Starr K.P., Qaiyumi S. The effect of application of aquaphor on skin condition, fluid requirements, and bacterial colonization in very low birth weight infants. J Perinatol. 1999;19(4):278–283.
    1. Nopper A.J., Horii K.A., Sookdeo-Drost S. Topical ointment therapy benefits premature infants. J Pediatr. 1996;128(5 Pt 1):660–669.
    1. Mannelli I., Reigada R., Suarez I. Functionalized surfaces with tailored wettability determine influenza a infectivity. ACS Appl Mater Interfaces. 2016;8(24):15058–15066.

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