title: Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Extremely premature (birth weight < 1250 g) infants are at high risk for acquiring late-onset sepsis and necrotizing enterocolitis, which are associated with significant mortality and morbidity. Own mother's milk contains protective (immune and trophic) biofactors which provide antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory functions, enhance intestinal microbiota, and promote intestinal maturation. Many of these biofactors are most highly concentrated in the milk expressed by mothers of extremely premature infants. However, since extremely premature infants do not receive oral milk feeds until 32 weeks post-conceptional age, they lack the potential benefit provided by milk (biofactor) exposure to oropharyngeal immunocompetent cells, and this deficiency could contribute to late-onset sepsis and necrotizing enterocolitis. Therefore, oropharyngeal administration of own mother's milk may improve the health outcomes of these infants.
  
  
  OBJECTIVE
  To compare the effects of oropharyngeal administration of mother's milk to a placebo, for important clinical outcomes, including (1A) reducing the incidence of late-onset sepsis (primary outcome) and (1B) necrotizing enterocolitis and death (secondary outcomes). To identify the biomechanisms responsible for the beneficial effects of oropharyngeal mother's milk for extremely premature infants, including; (2A) enhancement of gastrointestinal (fecal) microbiota (2B) improvement in antioxidant defense maturation or reduction of pro-oxidant status, and (2C) maturation of immunostimulatory effects as measured by changes in urinary lactoferrin.
  
  
  METHODS
  A 5-year, multi-center, double-blind, randomized controlled trial designed to evaluate the safety and efficacy of oropharyngeal mother's milk to reduce the incidence of (1A) late-onset sepsis and (1B) necrotizing enterocolitis and death in a large cohort of extremely premature infants (n = 622; total patients enrolled). Enrolled infants are randomly assigned to one of 2 groups: Group A infants receive 0.2 mL of own mother's milk, via oropharyngeal administration, every 2 hours for 48 hours, then every 3 hours until 32 weeks corrected-gestational age. Group B infants receive a placebo (0.2 mL sterile water) following the same protocol. Milk, urine, oral mucosal swab, and stool samples are collected at various time points, before, during and after the treatment periods. Health outcome and safety data are collected throughout the infant's stay.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT02116699 on 11 April 2014. Last updated: 26 May 2015.
authors.affiliation: NorthShore University HealthSystem, Evanston, IL, USA. nrodriguez@northshore.org.|University of Chicago Pritzker School of Medicine, Chicago, IL, USA. nrodriguez@northshore.org.|Clinician Researcher, Pritzker School of Medicine, Neonatal Nurse Practitioner, NorthShore University HealthSystem, 2650 Ridge Ave, Evanston, IL, 60201, USA. nrodriguez@northshore.org.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Rodriguez
authors.affiliation: Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain. Maximo.Vento@uv.es.
authors.forename: Maximo
authors.initials: M
authors.lastname: Vento
authors.affiliation: University of Chicago Pritzker School of Medicine, Chicago, IL, USA. eclaud@peds.bsd.uchicago.edu.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Claud
authors.affiliation: NorthShore University HealthSystem, Evanston, IL, USA. CWang3@northshore.org.
authors.forename: Chihsiung E
authors.initials: CE
authors.lastname: Wang
authors.affiliation: NorthShore University HealthSystem, Evanston, IL, USA. mcaplan@northshore.org.|University of Chicago Pritzker School of Medicine, Chicago, IL, USA. mcaplan@northshore.org.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Caplan
mesh_terms: D001724:Birth Weight; D002985:Clinical Protocols; D003126:Colostrum / Q000737:chemistry / Q000276:immunology; D004311:Double-Blind Method; D004750:Enteral Nutrition / Q000009:adverse effects / Q000379:methods*; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D005260:Female; D005865:Gestational Age; D017052:Hospital Mortality; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007227:Infant Nutritional Physiological Phenomena; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D008297:Male; D009752:Nutritional Status; D054238:Perinatal Mortality; D011247:Pregnancy; D012107:Research Design; D012307:Risk Factors; D018805:Sepsis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States