Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g

Abstract

Background: Lactoferrin (LF) is a broad-spectrum antimicrobial and immunomodulatory milk glycoprotein.

Objective: To determine the effect of bovine LF on the prevention of the first episode of late-onset sepsis in Peruvian infants.

Methods: We conducted a pilot randomized placebo-controlled double blind study in infants with a birth weight (BW) less than 2500g in 3 Neonatal Units in Lima. Patients were randomized to receive bovine LF 200mg/kg/d or placebo for 4 weeks.

Results: One hundred and ninety neonates with a BW of 1591 ± 408 g and a gestational age of 32.1 ± 2.6 weeks were enrolled. Overall, 33 clinically defined first late-onset sepsis events occurred. The cumulative sepsis incidence in the LF group was 12/95 (12.6%) versus 21/95 (22.1%) in the placebo group, and 20% (8/40) versus 37.5% (15/40) for infants less than or equal to 1500 g. The hazard ratio of LF, after adjustment by BW, was 0.507 (95% CI: 0.249-1.034). There were 4 episodes of culture-proven sepsis in the LF group versus 4 in the placebo group. Considering that children did not received the intervention until the start of oral or tube feeding, we ran a secondary exploratory analysis using time since the start of the treatment; in this model, LF achieved significance. There were no serious adverse events attributable to the intervention.

Conclusions: Overall sepsis occurred less frequently in the LF group than in the control group. Although the primary outcome did not reach statistical significance, the confidence interval is suggestive of an effect that justifies a larger trial.

Trial registration: ClinicalTrials.gov NCT01264536.

Conflict of interest statement

Conflict of Interest: The authors have no conflicts of interests to disclose, and declare that the study sponsors (Gates Foundation and NICHD) had no role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the manuscript for publication. Dr. Theresa J. Ochoa, corresponding author, wrote the first draft of the manuscript, and did not receive any form of payment for its production.

Figures

Figure 1

Study flow diagram. Enrollment: 375 neonates were assessed for eligibility. Allocation: 95 were randomized to LF and 95 to placebo; all received the allocated intervention. Follow-up: there were 7 and 3 drop-outs in the LF and placebo groups respectively. None were excluded from the analysis.

Figure 2

Kaplan-Meier survival estimates: time to event of late-onset sepsis by treatment group. Blue line: lactoferrin; red line: placebo; blue shadow: lactoferrin 95% confidence interval; red shadow: placebo 95% confidence intervals. LOS: Late-onset sepsis