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

Nancy A Rodriguez, Maximo Vento, Erika C Claud, Chihsiung E Wang, Michael S Caplan, Nancy A Rodriguez, Maximo Vento, Erika C Claud, Chihsiung E Wang, Michael S Caplan

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.

Objectives: 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/design: 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.

Trial registration: ClinicalTrials.gov identifier: NCT02116699 on 11 April 2014. Last updated: 26 May 2015.

Figures

Fig. 1
Fig. 1
Timeline of the study. After informed consent is obtained, the infant is enrolled, randomized, and begins receiving treatments. The treatments are given until the infant reaches 32 weeks CGA. Health outcome data is collected throughout the infant’s hospitalization until NICU discharge. CGA, corrected gestational age; NICU, neonatal intensive care unit
Fig. 2
Fig. 2
Study flow chart. Enrolled infants are randomized to receive either own mother’s milk or a placebo during the initial treatment period and the extended treatment period. Biological specimens (milk, urine, stool and swab of oral mucosa) are collected at specific time-points as depicted. CGA, corrected gestational age; L-OS, late-onset sepsis; NEC, necrotizing enterocolitis

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