Forgive me if you are already convinced, but I remain somewhat sceptical of the benefits of routinely painting the inside of the preterm infant’s mouth with colostrum. Even though I have supported the introduction of the practice on our NICU, it seems to me to be a bit flaky, to use the scientific term. Can this intervention really have the enormous benefits for the outcomes of our babies that are claimed? I have read the theoretical justifications, and the small mechanistic studies showing impacts on IgA, and maybe on lactoferrin, but the practice has become widely promoted, with catchy names (Oral Immune Therapy) and 3 letter abbreviations- OIT, without good evidence to support it.

What is the evidence of clinical benefit? Does it only work with Mother’s own Colostrum? Does it have to be fresh? Is there a dose response?

There is a Cochrane review, which dates from 2018, they found 6 studies with 335 infants included, and no clear benefit of anything. There are several more recent Systematic Reviews, of varying quality. One of the better very recent ones seems to have been performed following the appropriate standards (Kumar J, et al. Oropharyngeal application of colostrum or mother’s own milk in preterm infants: a systematic review and meta-analysis. Nutr Rev. 2023;81(10):1254-66). This includes 17 RCTs, of varying quality, and I did a quick search and was unable to find anything newer that wasn’t in this SR. Of note, in many of the trials they included, the enteral feeding schedules of the included babies were far from being standard-of-care; large numbers of the babies received artificial formula and some were kept npo during the first days of life. The intervention is also somewhat variable, although 0.2mL of colostrum q3h for 2 to 3 days is the most frequent, some have used greater volumes, or much longer durations, switching to Mother’s own Milk as time went on.

Despite all the hype, there is little evidence of benefit, but the small numbers, and poor quality, mean there remains a real possibility of a major impact on NEC, the RR of stage 2/3 NEC was 0.65 (95% CI 0.36-1.2, n=1089), and of late-onset sepsis was 0.72 (0.56-0.92, n=1482), the latter being very-low quality evidence by GRADE.

Even that NEC result is almost entirely dependent on a single study from China (n=252), which was retrospectively registered, and was terminated early because of an early apparent advantage of the colostrum group, who had much less NEC. The overall incidence of NEC in the controls (<33 weeks gestation, mean GA 30 weeks in each group) was over 10%, they do not appear to have had donor milk available, and it is really difficult to understand some of the data. The late-onset-sepsis result is also largely dependent on this single study.

I do not understand why so many trials from China are retrospectively registered, everyone knows that it is essential to register trials, but doing so retrospectively makes a mockery of the system. It means we can have no confidence that the primary outcome has not been changed, or that the analysis is what was planned. Systematic reviews should always consider this to be a huge red flag, and note it in Risk of Bias evaluations.

This SR illustrates the difficulty in doing trials to prevent NEC; babies in future trials should have optimal evidence-based NEC prevention already in place, with early human milk feeds, standardised protocols and multi-component probiotics; with such approaches NEC becomes less frequent, so very large numbers of subjects are required. Perhaps the only way to do such trials in the future will be performing registry trials with cluster-randomisation. Oro-pharyngeal colostrum administration is, on the other hand, almost certainly quite safe, and, other than the logistic difficulties in ensuring early colostrum expression, and tracking the stuff from mother to baby, quite inexpensive. Perhaps we should all do it anyway, and accept that we will never really know if it is making a difference to NEC or to late-onset sepsis?

I hate to suggest that, but perhaps we can all agree that OIT (!) is almost certainly harmless and just might have measurable benefits. Introducing frequent oropharyngeal painting with uninfected fresh maternal colostrum as a routine practice would have the additional benefit of strengthening efforts to support mothers in the very early expression of their breast milk. For which there is a great deal of observational evidence (such as this very recent publication) that it helps to ensure good milk production over the first weeks of NICU hospitalisation.