Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF´s role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide.

Lactoferrin (LF) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to determine the effect of bovine lactoferrin (bLF) in the prevention of SARS-CoV-2 infection in health care personnel. A randomized, double-blinded, placebo-controlled clinical trial was conducted in two tertiary hospitals that provide care to patients with SARS-CoV-2 infection in Lima, Peru. Daily supplementation with 600 mg of enteral bLF versus placebo for 90 days was compared. Participants were weekly screened for symptoms suggestive of SARS-CoV-2 infection and molecular testing was performed on suspected episodes. A serological test was obtained from all participants at the end of the intervention. The main outcome included symptomatic and asymptomatic cases. A sub-analysis explored the time to symptomatic infection. Secondary outcomes were the severity, frequency, and duration of symptomatic infection. The study was prematurely cancelled due to the availability of vaccines against SARS-CoV-2 in Peru. 209 participants were enrolled and randomized, 104 received bLF and 105 placebo. SARS-CoV-2 infection occurred in 11 (10.6%) participants assigned to bLF and in 9 (8.6%) participants assigned to placebo without significant differences (Incidence Rate Ratio = 1.23, 95%CI 0.51–3.06, p-value = 0.64). There was no significant effect of bLF on time to symptomatic infection (Hazard Ratio = 1.61, 95%CI 0.62–4.19, p-value = 0.3). There were no significant differences in secondary outcomes. A significant effect of bLF in preventing SARS-CoV-2 infection was not proven. Further studies are needed to assess the effect of bLF supplementation on SARS-CoV-2 infection. Clinical trial registration ClinicalTrials.gov Identifier: NCT04526821, https://clinicaltrials.gov/ct2/show/NCT04526821?term=LACTOFERRIN&cond=COVID-19&cntry=PE&city=Lima&draw=2&rank=1 . Supplementary Information The online version contains supplementary material available at 10.1007/s10534-022-00477-3.