Impact of colostrum oropharyngeal immunotherapy on postnatal growth in preterm infants based on early gut microbiota-host interaction patterns: protocol for a randomized controlled trial.

Abstract

Background: Extrauterine growth restriction (EUGR), prevalent and severe in very preterm infants (< 32 weeks' gestation), means discharge growth values (weight, head circumference, or length) are ≤ 10th percentile on the Fenton 2013 chart. Many of these infants fast or have delayed oral feeding soon after birth. Oropharyngeal colostrum administration, using a syringe or sterile swab, is an alternative to early enteral colostrum feeding. As the effectiveness of oropharyngeal colostrum administration in reducing the incidence of EUGR in preterm infants remains unclear, a randomized trial design is crucial for addressing this question. This proposed study protocol investigates the impact of oropharyngeal colostrum administration on the time to regain birth weight and postnatal growth in very preterm infants, based on the interaction between early gut microbiota and the host.

Methods: We plan to perform this multicenter randomized controlled trial by recruiting 260 very preterm infants from September 2025 to August 2028. The study will be conducted at five neonatal intensive care units (NICUs) in Jiangsu Province, China. The study population will be randomly assigned to either the oropharyngeal colostrum administration group or the placebo (normal saline) group. The intervention will commence within 48-72 h of birth and and will be administered continuously for a duration of 5 days, with stool samples collected from the preterm infants before and after the intervention. The primary outcome measure is the incidence of EUGR at discharge, while the secondary outcome measures include differences in the time to regain birth weight and gut microbiota between groups. This study will use a multivariate logistic regression to evaluate the association between oropharyngeal colostrum administration and EUGR, multiple tests (T-test, Wilcoxon, repeated measures analysis of variance) for gut microbial diversity differences, and a generalized linear model for the association between the intervention and gut microbiota composition.

Discussion: This study aims to provide a scientific basis for the clinical application of oropharyngeal colostrum administration in preterm infants through rigorous clinical trials and intestinal flora analyses and to provide new insights into intervention strategies for EUGR in preterm infants.

Trial registration: ClinicalTrials.gov identifier: NCT07082881. Registered 16 July 2025.