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Background: infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods: in this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings: we recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention.Interpretation: enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding: UK National Institute for Health Research Health Technology Assessment programme (10/57/49).

Background: Oxygen saturation (Spo2) monitors are commonly used to determine the need for supplemental oxygen. We aimed to describe the range of arterial oxygen tensions (Pao2) observed in preterm infants at saturation levels targeted in current trials. Methods: In a cohort of 98 consecutive infants born at

Introduction: Hyperoxia and variable oxygenation are associated with morbidity in preterm infants. The optimal range of oxygen tensions is not known. This study aimed to determine whether care based on transcutaneous oxygen tension (TcPo2) or saturation (Spo2) monitoring is associated with less time spent with high oxygen tension and less variability of oxygenation. Methods: Spo2 and TcPo2 were measured simultaneously during two 3-h study periods allocated in random order. During one period supplemental oxygen was adjusted according to TcPo2 (target range 6.0–9.0 kPa) and during the other according to Spo2 (target range 86–94%). During each period, readings from the second monitor were not displayed. Both TcPo2 and Spo2 were downloaded every second. For each period the mean level and the variability (standard deviation) of Spo2 and TcPo2 and the percentage of time spent above and below target range were calculated and compared. Results: 19 infants, 13 ventilated and 6 on continuous positive airway pressure, were studied at mean corrected gestational age of 27.2 weeks and mean postnatal age of 6.8 days. Their mean fraction of inspired oxygen at the start of the study was 0.34. Care based on Spo2 monitoring was associated with more time spent with high oxygen tension (median increase 2.62%, p = 0.01), more time with low oxygen tension (median increase 17.41%, p = 0.01), more variability in oxygen tension (median increase 0.28 kPa, p = 0.02) and more variability in oxygen saturation (median increase 0.82%, p = 0.01) than care based on TcPo2 monitoring. Conclusion: Within the target ranges studied Spo2 monitoring was associated with significantly more variable oxygenation than TcPo2 monitoring.