Lactoferrin and infection in very preterm infants

This is the most instructive claim on the site, because it is the one where the evidence changed.

What the early trials suggested

Lactoferrin is a normal constituent of human colostrum and milk. Very preterm infants, fed early and often on formula or donor milk, receive far less of it than a term infant would. Several small randomized trials examined whether supplementing the enteral diet with bovine lactoferrin reduced infection, and reported that it did. The finding was biologically plausible, consistent across those trials, and widely repeated.

What the large trial found

The ELFIN trial recruited 2,203 infants born before 32 weeks' gestation across 37 UK hospitals, randomizing them to bovine lactoferrin at 150 mg/kg per day or to sucrose, until 34 weeks' postmenstrual age. Parents, caregivers and outcome assessors were blinded to assignment.

Late-onset infection occurred in 316 of 1,093 infants in the lactoferrin group and 334 of 1,089 in the control group. The risk ratio, adjusted for the minimization factors, was 0.95, with a 95% confidence interval of 0.86 to 1.04 and a p value of 0.233.

The trial's own conclusion was unambiguous: enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants, and the data do not support its routine use for that purpose.

Why this grade is "Not supported" rather than "Insufficient"

The distinction matters. An insufficient grade means nobody has looked properly. Here somebody did look properly, at scale, with blinding and a pre-specified primary outcome, and the effect the smaller trials had reported did not appear.

That is a stronger and more useful result than silence. It is also the single most common way a promising nutritional intervention ends, and the version of events that tends not to travel: the small positive trials remain in circulation and are still cited, while the large null trial is mentioned less often.

What it does not mean

It does not mean lactoferrin does nothing anywhere. It means this specific claim, in this specific population, at this dose, was tested and not supported. Other claims about lactoferrin carry their own grades, arrived at separately.

Two serious adverse events in the lactoferrin group were assessed as possibly related to the intervention: one case of blood in stool, and one death following intestinal perforation. With 16 serious adverse events in the lactoferrin group against 10 in the control group, the trial was not powered to characterize rare harms, and no conclusion about them should be drawn in either direction.