In RCTs , pasteurized human donor milk , as opposed to formula , reduced NEC but not infections or mortality .
Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections , NEC , or mortality .
Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality .
A meta- analysis sensitivity approach found multiple-strain ( but not single-strain ) probiotics to be highly effective in reducing NEC and mortality .
Thus , selected food components may help to improve outcomes in preterm infants
Observational studies demonstrating reduced rates of infections , necrotizing enterocolitis ( NEC ) , and mortality in preterm infants fed their own mother ’s milk , as opposed to formula , have prompted endeavors to achieve similar effects with the right choice of food and food additives .
In a systematic review of meta-analyses and r and omized controlled trials ( RCTs ) , we considered nutritional interventions aim ed at reducing the rates of infections , NEC , or mortality in very preterm infants .
Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT.
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 . OBJECTIVE To determine whether or not enteral supplementation with bovine lactoferrin ( The Tatua Cooperative Dairy Company Ltd , Morrinsville , New Zeal and ) reduces the risk of late-onset infection ( acquired > 72 hours after birth ) and other morbidity and mortality in very preterm infants . DESIGN R and omised , placebo-controlled , parallel-group trial . R and omisation was via a web-based portal and used an algorithm that minimised for recruitment site , weeks of gestation , sex and single versus multiple births . SETTING UK neonatal units between May 2014 and September 2017 . PARTICIPANTS Infants born at < 32 weeks ' gestation and aged < 72 hours at trial enrolment . INTERVENTIONS Eligible infants were allocated individually ( 1 : 1 ratio ) to receive enteral bovine lactoferrin ( 150 mg/kg/day ; maximum 300 mg/day ) or sucrose ( British Sugar , Peterborough , UK ) placebo ( same dose ) once daily from trial entry until a postmenstrual age of 34 weeks . Parents , caregivers and outcome assessors were unaware of group assignment . OUTCOMES Primary outcome - microbiologically confirmed or clinical ly suspected late-onset infection . Secondary outcomes - microbiologically confirmed infection ; all-cause mortality ; severe necrotising enterocolitis ( NEC ) ; retinopathy of prematurity ( ROP ) ; bronchopulmonary dysplasia ( BPD ) ; a composite of infection , NEC , ROP , BPD and mortality ; days of receipt of antimicrobials until 34 weeks ' postmenstrual age ; length of stay in hospital ; and length of stay in intensive care , high-dependency and special-care setting s. RESULTS Of 2203 enrolled infants , primary outcome data were available for 2182 infants ( 99 % ) . In the intervention group , 316 out of 1093 ( 28.9 % ) infants acquired a late-onset infection versus 334 out of 1089 ( 30.7 % ) infants in the control group [ adjusted risk ratio ( RR ) 0.95 , 95 % confidence interval ( CI ) 0.86 to 1.04 ] . There were no significant differences in any secondary outcomes : microbiologically confirmed infection ( RR 1.05 , 99 % CI 0.87 to 1.26 ) , mortality ( RR 1.05 , 99 % CI 0.66 to 1.68 ) , NEC ( RR 1.13 , 99 % CI 0.68 to 1.89 ) , ROP ( RR 0.89 , 99 % CI 0.62 to 1.28 ) , BPD ( RR 1.01 , 99 % CI 0.90 to 1.13 ) , or a composite of infection , NEC , ROP , BPD and mortality ( RR 1.01 , 99 % CI 0.94 to 1.08 ) . There were no differences in the number of days of receipt of antimicrobials , length of stay in hospital , or length of stay in intensive care , high-dependency or special-care setting s. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group . CONCLUSIONS Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection , mortality or other morbidity in very preterm infants . FUTURE WORK Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta- analysis with data from other trials . A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants . TRIAL REGISTRATION Current Controlled Trials IS RCT N88261002 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 22 , No. 74 . See the NIHR Journals Library website for further project information . This trial was also sponsored by the University of Oxford , Oxford , UK . The funder provided advice and support and monitored study progress but did not have a role in study design or data collection , analysis and interpretation
In RCTs , pasteurized human donor milk , as opposed to formula , reduced NEC but not infections or mortality .
Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections , NEC , or mortality .
Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality .
A meta- analysis sensitivity approach found multiple-strain ( but not single-strain ) probiotics to be highly effective in reducing NEC and mortality .
Thus , selected food components may help to improve outcomes in preterm infants
Observational studies demonstrating reduced rates of infections , necrotizing enterocolitis ( NEC ) , and mortality in preterm infants fed their own mother ’s milk , as opposed to formula , have prompted endeavors to achieve similar effects with the right choice of food and food additives .
In a systematic review of meta-analyses and r and omized controlled trials ( RCTs ) , we considered nutritional interventions aim ed at reducing the rates of infections , NEC , or mortality in very preterm infants .