Contents:
Why Two Drops Matter
Evidence from Reviews and Trials
Implementation and Practice
Clinical Implications
At the 2025 Medela Americas Symposium, Dr. Jae Kim noted that oral immune therapy (OIT) has been adopted in neonatal intensive care units more quickly than interventions with far stronger levels of evidence. This point highlights something important. Even though research findings about OIT vary by review and analytic approach, clinicians are using it because the physiology makes sense, it is easy to implement, and there is little to no risk. Two recent systematic reviews illustrate the landscape. A 2022 meta-analysis found significant reductions in late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), while shortening the time to reach full enteral feeds and duration of hospital stay.1 A 2023 review, evaluating many of the same randomized trials, reported signals for lower risks of sepsis and any-stage NEC but rated the certainty of evidence as low to very low.2 Despite this, the authors state OIT therapy is a low cost intervention, has minimal risk of harm, and may be considered as a routine practice for preterm neonates.
OIT aligns with what we already know about colostrum. Colostrum is not just early milk. It is immunologically distinct from mature milk and nothing like commercial milk formula.
The period immediately following birth is extremely dangerous for the newborn infant due to their immature immune system, and their now exposure to an enormous amount of pathogenic microorganisms. For this reason, colostrum contains more bioactive immunologic components than mature milk, it carries very high levels of secretory immunoglobulin A (sIgA), lactoferrin, human milk oligosaccharides (HMOs), cytokines such as TGF-β, Epidermal Growth Factor (EGF) and live immune cells.3,4 Each of these components has a role in protecting the newborn, sealing the intestinal barrier, and training the immune system to respond appropriately. Applying a small amount of colostrum directly to the oral mucosa of a preterm infant builds on this natural biology.
Secretory IgA antibodies perform their function locally, on the surface of the mucous membranes. They bind microorganisms and pathogens like bacteria and viruses, preventing their adhesion to the organ’s epithelium. Their protective function is focused on the gastrointestinal and respiratory systems which makes them so potent in preventing infectious diarrhea, inflammatory bowel disease, necrotizing enterocolitis and acute respiratory infections3,4
Why Two Drops Matter
OIT protocols often recommend 0.1 to 0.2 mL of fresh mother’s colostrum placed inside each cheek every few hours until the infant is ready for full feeds.5 These tiny volumes may look inconsequential, but they deliver an immune-rich dose. The colostrum coats the mucosa, tightens cell junctions, and influences which microbes colonize the infant gut.3
This is best remembered as the 3 Cs:
- Coats: SIgA and lactoferrin coat the oral cavity and oropharynx to bind microbes and antigens.3,4
- Closes: growth factors and HMOs help close intestinal junctions and strengthen the gut barrier.6,7
- Coaches: repeated exposure provides tolerogenic signals that coach the immune system to distinguish friend from foe.8
OIT provides local immune protection in the oropharynx while also priming the mucosal immune system. Several studies show that these small doses increase levels of immune proteins such as sIgA and lactoferrin in the infant’s urine, suggesting systemic immune activation.5 The strongest and most consistent clinical signal is the reduction in late-onset sepsis. Randomized trials and meta-analyses repeatedly show this, even though NEC prevention results remain more variable across analyses.1,2,5,9 No trial has identified harms, which strengthens the case for routine use.1,2
Evidence from Reviews and Trials
The research base includes multiple randomized and observational trials. A 2022 meta-analysis found significant reductions in LOS and NEC, no effect on BPD, and overall support for safety.1 A 2023 systematic review found associations with reduced sepsis and any-stage NEC, but graded the certainty of evidence as low to very low.2 A sepsis-focused meta-analysis confirmed a significant reduction in culture‑proven sepsis among preterm infants who received OIT.9
There are also reasons to believe the benefits of very early human milk exposure may extend beyond immediate infection protection. In very preterm infants, predominant human milk intake in the first postnatal month has been associated with improved neurocognitive outcomes at 7 years.10 Colostrum is rich in bioactive factors, and emerging experimental work underscores that the diet at birth can shape growth trajectories in ways that are at least partly independent of microbiota effects.11
Implementation and Practice
OIT has spread quickly because it is feasible, safe, and inexpensive. The challenge is to ensure it is done in a consistent and standardized way.
At the 2025 Medela Americas Symposium, Kristina Tucker and colleagues presented a poster of their work showing that OIT is not only about immune protection but also about strengthening the bond between mothers and their infants in the NICU.12 Collecting a few drops and applying them directly becomes a shared ritual that validates the mother’s contribution and reassures her that even the smallest amount of milk matters. This parent connection can be as powerful as the immunologic benefit.
A 2025 quality improvement study published in Breastfeeding Medine underscored how essential parent‑centered care is in the NICU. Snell and colleagues (including Hagan and Tucker) showed that an educational bundle—emphasizing early pumping, frequent expression, and the value of OIT—significantly increased OIT delivery and raised the proportion of very low birthweight infants receiving higher doses (≥90%) of mother’s own milk in the first 28 days of life.13
Their findings reflect what many clinicians see at the bedside. When parents are supported from the start, they move from a sense of helplessness to feeling empowered as their baby’s primary caregiver. That early shift, even with simple actions like offering tiny drops of colostrum in the first days, contributes to higher milk provision in more than 90 percent of parents. Structured education and consistent coaching help families and staff protect early colostrum supply and ensure that OIT is delivered reliably.
Clinical Implications
Mothers should be encouraged to provide colostrum for their hospitalized neonates, regardless of their long‑term feeding plans. They may bring freshly expressed colostrum to the bedside for supervised oral care or express milk directly at the bedside for immediate administration. Parents should be supported and guided to participate in oral care during routine hands‑on caregiving, promoting both bonding and early protective benefits for the infant.
For clinicians, OIT should be practiced with the same discipline as any other therapy.
Start within the first hour after birth when feasible, repeating every 2 to 3 hours.
Use standard dosing of 0.1 to 0.2 mL in each cheek and document it in the medical record as “oral immune therapy.”
Integrate OIT into bundles that include early milk expression to support colostrum supply.
Partner with parents by explaining the physiology and showing how every drop counts™.
Do not use donor milk if maternal colostrum is unavailable. At present, there are no known studies that have investigated the use of donor human milk for oral care. In theory, donor human milk will not provide the same immune enhancing benefits as pasteurization significantly decreases lactoferrin and other immune enhancing factors in human milk.
Conclusion
Mothers should be encouraged to provide colostrum for their hospitalized neonates, regardless of their plans for feeding. Freshly expressed colostrum can be brought to the bedside for supervised oral immune therapy (OIT), or expressed at the bedside for immediate use. Colostrum remains one of the most effective tools we have in the first days of life. Even the smallest volumes provide meaningful immune protection, and supporting parents as they offer those first drops helps them step confidently into their role in care. When we guide families through this early practice, we strengthen the infant’s defenses and reinforce that every drop counts™.
