Oropharyngeal administration of mother’s colostrum…

Rodriguez, N.A., Vento, M., Claud, E.C. et al. Oropharyngeal administration of mother’s colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial. Trials 16, 453 (2015). https://doi.org/10.1186/s13063-015-0969-6

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.

Keywords
Breast milk, Human milk, Mother’s milk, Colostrum, Oropharyngeal, Oral immune, Oral care, Premature, Extremely low birth weight, Very low birth weight, Oral immune therapy.

Disponível em: <https://trialsjournal.biomedcentral.com/>

Comentários:
Apesar do grande avanço da medicina neonatal, as taxas de morbidade e mortalidade permanecem altas nos prematuros extremos, frequentemente relacionados a sepse tardia e enterocolite necrotizante. Esses bebês são, devido à imaturidade, funcionalmente imunodeficientes, têm uma mucosa intestinal imatura, além de serem submetidos a diversos procedimentos invasivos. Esta situação desfavorável favorece tanto a translocação bacteriana, quanto a invasão direta da bactéria a corrente sanguínea. O uso do leite materno tem mostrado vantagens em relação a saúde destes pré-termos extremos. Isto tem sido relacionado a múltiplos fatores de proteção, imunológico e trófico, contidos no leite, com função antimicrobiana, anti-inflamatória, antioxidante e imunomodulatória que aumentam a microbiota intestinal e promovem a maturação intestinal. Este é um estudo prospectivo, multicêntrico, desenhado para avaliar a segurança e eficácia da administração de leite humano da própria mãe em pré-termos menores 1250g. Este trabalho encontra-se em andamento e amostra calculada para se atingir uma força estatística significativa é de 498 crianças (249 em cada grupo). Os autores esperam finalizar o recrutamento em setembro de 2018 e apresentar o resultado final em 2019.