Oropharyngeal administration of mother’s colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial

Abstract

BackgroundExtremely 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.ObjectivesTo 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/DesignA 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.Trial registrationClinicalTrials.gov identifier: NCT02116699 on 11 April 2014. Last updated: 26 May 2015

Effect of oropharyngeal colostrum therapy in the prevention of necrotising enterocolitis among very low birthweight neonates: A meta‐analysis of randomised controlled trials

“…Hence, the power to analyse these outcomes is not sufficient. A multicentric double‐blinded large RCT ( n = 622 neonates) is ongoing that may achieve the desired outcomes. There is one Cochrane systematic review in process that aims to assess the role of oropharyngeal colostrum in the prevention of morbidity and mortality in preterm (<37 weeks of gestation) neonates .…”

Immunonutrition for Preterm Infants

“…Although it is feasible to deliver maternal colostrum to very preterm infants via an intragastric tube, mothers may be able to provide only very small volumes during the first few days after birth. Another option is instilling these small amounts (typically < 0.5 mL) into the infant’s oropharyngeal cavity [22]. The rationale for this approach is that the oral epithelium contains receptors for the immunological and trophic factors in colostrum and that oropharynx-associated lymphoid tissue is a key interface between the infant’s immune system and the enteric microbial flora [10].…”

“…The rationale for this approach is that the oral epithelium contains receptors for the immunological and trophic factors in colostrum and that oropharynx-associated lymphoid tissue is a key interface between the infant’s immune system and the enteric microbial flora [10]. Trial evidence of benefits is currently limited, but large, high-quality randomised controlled trials to evaluate more precisely and reliably the effects of oropharyngeal colostrum on outcomes for preterm infants are planned or in progress [22, 23]. …”

Potential benefits of colostrum in gastrointestinal diseases

“…Animals fed with BC had a longer intestinal transit time, higher weight gain, absorptive capacity and enzyme activities compared to piglets fed with infant formula. At the same time, BC reduced NEC incidence, pro-inflammatory cytokines concentration such as IL-8 and reduced histological lesions (169). BC proved to have beneficial effects on NEC development and intestinal function in a piglet model and these data were confirmed by an in vitro study in which a modulatory action of colostrum proteins in cytokines secretion from bacteria-stimulated murine bone marrowderived dendritic cells was observed (170).…”