Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants.
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ABSTRACT:
SUBMITTER: Pammi M
PROVIDER: S-EPMC7106972 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants.
Pammi Mohan M Suresh Gautham G
The Cochrane database of systematic reviews 20200331
<h4>Background</h4>Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.<h4>Objectives</h4>To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilatio ...[more]
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Project description:BackgroundLactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.ObjectivesPrimary objective 1. To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates Secondary objectives 1. To determine the effects of lactoferrin supplementation to enteral feeds to prevent neonatal sepsis and/or NEC on duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later2. To determine the adverse effects of lactoferrin supplementation for prophylaxis of neonatal sepsis and/or NECWhen data were available, we analyzed the following subgroups.1. Gestational age < 32 weeks and 32 to 36 weeks2. Birth weight < 1000 g (extremely low birth weight (ELBW) infants) and birth weight < 1500 g (very low birth weight (VLBW) infants)3. Type of feeding: breast milk versus formula milk SEARCH METHODS: We used the search strategy of the Cochrane Neonatal Review Group (CNRG) to update our search in December 2016. We searched the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as trial registries and conference proceedings.Selection criteriaRandomized controlled trials (RCTs) evaluating oral lactoferrin at any dose or duration to prevent sepsis or NEC in preterm neonates.Data collection and analysisReview authors used standard methods of the CNRG.Main resultsThis review includes six RCTs. Trial results show that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical risk ratio (RR) 0.59, 95% confidence interval (CI) 0.40 to 0.87; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 17, 95% CI 10 to 50; six trials, 886 participants; low-quality evidence) and NEC stage II or III (typical RR 0.40, 95% CI 0.18 to 0.86; typical RD -0.04, 95% CI -0.06 to -0.01; NNTB 25, 95% CI 17 to 100; four studies, 750 participants; low-quality evidence). Lactoferrin supplementation did not have an effect on "all-cause mortality" (typical RR 0.65, 95% CI 0.37 to 1.11; typical RD -0.02, 95% CI -0.05 to 0; six studies, 1041 participants; low-quality evidence).Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.27, 95% CI 0.12 to 0.60; RD -0.13, 95% CI -0.19 to -0.06; NNTB 8, 95% CI 5 to 17; one study, 321 participants; low-quality evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; one study, 496 participants; low-quality evidence), but not "all-cause mortality" (low-quality evidence).Lactoferrin supplementation to enteral feeds with or without probiotics decreased bacterial and fungal sepsis but not CLD or length of hospital stay (low-quality evidence). Investigators reported no adverse effects and did not evaluate long-term neurological outcomes and PVL.Authors' conclusionsEvidence of low quality suggests that lactoferrin supplementation to enteral feeds with or without probiotics decreases late-onset sepsis and NEC stage II or III in preterm infants without adverse effects. Completed ongoing trials will provide data from more than 6000 preterm neonates, which may enhance the quality of the evidence. Clarification regarding optimal dosing regimens, types of lactoferrin (human or bovine), and long-term outcomes is needed.
| S-EPMC6481465 | biostudies-literature
Project description:BackgroundSeveral clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta‑analysis with trial sequential analysis (TSA).MethodsWe searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed.ResultsNine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02, P = 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52, P = 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57, P = 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13, P = 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32, P = 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94, P = 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08, P = 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06, P = 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84, P = 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required.ConclusionsLimited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice.
| S-EPMC7426497 | biostudies-literature
Project description:BackgroundInfections 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.MethodsIn 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.FindingsWe 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.InterpretationEnteral 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.FundingUK National Institute for Health Research Health Technology Assessment programme (10/57/49).
| S-EPMC6356450 | biostudies-literature
Project description: Not available
| S-EPMC6478109 | biostudies-literature
Project description:Feeding practices around the time of packed red blood cell transfusion have been implicated in the subsequent development of necrotising enterocolitis (NEC) in preterm infants. Specifically, it has been suggested that withholding feeds around the time of transfusion may reduce the risk of subsequent NEC. It is important to determine if withholding feeds around transfusion reduces the risk of subsequent NEC and associated mortality. • To assess the benefits and risks of stopping compared to continuing feed management before, during, and after blood transfusion in preterm infants • To assess the effects of stopping versus continuing feeds in the following subgroups of infants: infants of different gestations; infants with symptomatic and asymptomatic anaemia; infants who received different feeding schedules, types of feed, and methods of feed delivery; infants who were transfused with different blood products, at different blood volumes, via different routes of delivery; and those who received blood transfusion with and without co-interventions such as use of diuretics • To determine the effectiveness and safety of stopping feeds around the time of a blood transfusion in reducing the risk of subsequent necrotising enterocolitis (NEC) in preterm infants SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), in the Cochrane Library; MEDLINE (1966 to 14 November 2018); Embase (1980 to 14 November 2018); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 November 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs. Randomised and quasi-randomised controlled trials that compared stopping feeds versus continuing feeds around the time of blood transfusion in preterm infants. Two review authors independently selected trials, assessed trial quality, and extracted data from the included studies. The search revealed seven studies that assessed effects of stopping feeds during blood transfusion. However, only one RCT involving 22 preterm infants was eligible for inclusion in the review. This RCT had low risk of selection bias but high risk of performance bias, as care personnel were not blinded to the study allocation. The primary objective of this trial was to investigate changes in mesenteric blood flow, and no cases of NEC were reported in any of the infants included in the trial. We were unable to draw any conclusions from this single study. The overall GRADE rating for quality of evidence was very low. Randomised controlled trial evidence is insufficient to show whether stopping feeds has an effect on the incidence of subsequent NEC or death. Large, adequately powered RCTs are needed to address this issue.
| S-EPMC6815687 | biostudies-literature
Project description:Necrotizing enterocolitis (NEC) is a critical intestinal emergency condition, which mainly occurs in preterm very low birth weight (PVLBW) infants. Despite remarkable advances in the care of PVLBW infants, with considerable improvement of the survival rate in recent decades, the incidence of NEC and NEC-related mortality have not declined accordingly. The fast progression from nonspecific signs to extensive necrosis also makes primary prevention the first priority. Recently, increasing evidence has indicated the important role of several nutrients in primary prevention of NEC. Therefore, the aim of this review is to summarize some potential immunomodulatory nutrients in the prevention of NEC, including bovine colostrum, probiotics, prebiotics (e.g., human milk oligosaccharides), long chain polyunsaturated fatty acids, and amino acids (glutamine, cysteine and N-acetylcysteine, l-arginine and l-citrulline). Based on current research evidence, probiotics are the most documented effective method to prevent NEC, while others still require further investigation in animal studies and clinical randomized controlled trials.
| S-EPMC4586529 | biostudies-literature
Project description:Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
| S-EPMC7922869 | biostudies-literature
Project description:Background/objectivesPrebiotics are increasingly recognized as an effective measure to promote health and prevent adverse health outcomes in preterm infants. We aimed to systematically review the randomized controlled trials (RCTs) in this area.Subjects/methodsRelevant studies from January 2000 to June 2018 were searched and selected from PubMed, Medline, Scopus, and the Cochrane Library. RCTs were included if they involved preterm infant participants, included a prebiotic intervention group, measured incidence of sepsis, feeding intolerance, mortality, time to full enteral feeding, necrotizing enterocolitis (NEC), length of hospital stay, and stool frequency as outcomes.ResultsEighteen RCTs (n?=?1322) were included in the final meta-analysis. Participants who took prebiotics showed significant decreases in the incidence of sepsis (with a risk ratio (RR) of 0.64, 95% CI: 0.51, 0.78), mortality (RR?=?0.58. 95% CI: 0.36, 0.94), length of hospital stay (mean difference (MD): -5.18, 95% CI: -8.94, -1.11), and time to full enteral feeding (MD: -0.99, 95% CI: -1.15, 0.83). The pooled effects showed no significant differences between intervention and control groups in relation to the morbidity rate of NEC (RR?=?0.79, 95% CI: 0.44, 1.44) or feeding intolerance (RR?=?0.87, 95% CI: 0.52, 1.45).ConclusionsThe results showed that the use of prebiotics with preterm infants is safe and can decrease the incidence of sepsis, mortality, length of hospital stay, and time to full enteral feeding but not NEC.
| S-EPMC6760619 | biostudies-literature
Project description:IntroductionLactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties.ObjectivesThe aim of this study was to determine the association of maternal LF intake and mother's own milk intake in the first 10 days of life on the prevention of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in the first 8 weeks of life in newborns with a birth weight <2,000 g.MethodsA retrospective cohort study was conducted, with the exposure being the consumption of mother's own LF and mother's own milk in the first 10 days of life, and the outcome being LOS, NEC, or death during days 11 and 56 of life, analyzed by Cox regression.ResultsTwo hundred and ninety-nine infants were enrolled, including 240 with human LF intake information. The average daily human LF intake over days 4-10 of life was 283 mg/kg/day (IQR 114-606 mg/kg/day). The hazard ratio (HR) of mother's own milk LF intake ≥100 mg/kg/day in days 4-10 for LOS, NEC, or death was 0.297 (95% CI 0.156-0.568, p < 0.001); the adjusted HR was 0.752 (95% CI 0.301-1.877, p = 0.541). The adjusted HR of mother's own milk cumulative intake (days 4-10) of 54-344 mL/kg (25-75 quartiles) for LOS, NEC, or death was 0.414 (95% CI 0.196-0.873, p = 0.02). Infants who developed an event (LOS, NEC, or death) had significantly less median daily human LF intake than those that did not (89 vs. 334 mg/kg/day, respectively, p < 0.0001).ConclusionConsumption of higher amounts of mother's own milk in the first days of life is associated with less infection, NEC, and death. Early human milk intake should be strongly encouraged in all newborns.
| S-EPMC7381382 | biostudies-literature
Project description:BackgroundIntestinal bile salts (BSs) may be implicated in NEC development. We hypothesized that fecal BS levels are higher in preterm infants at risk for NEC.MethodsWe compared the composition and concentration of fecal BSs in ten preterm infants who developed NEC (Bell's Stage ≥ II) with twenty matched control infants without NEC. Conjugated and unconjugated fecal BSs were measured after birth (T1) and twice prior to NEC (T2, T3). Data are presented as medians and interquartile ranges.ResultsGA and BW were similar in all preterms: ~27+4 weeks and ~1010 g. Age of NEC onset was day 10 (8-24). T1 was collected 2 (1-3) days after birth. T2 and T3 were collected 5 (5-6) days and 1 (0-2) day before NEC or at corresponding postnatal ages in controls. The composition of conjugated BSs did not differ between the two groups. Total unconjugated BSs were 3-fold higher before NEC compared to controls at corresponding ages (0.41 μmol/g feces (0.21-0.74) versus 0.14 μmol/g feces (0.06-0.46), p < 0.05).ConclusionFecal BS concentrations are higher in preterm infants who develop NEC compared to infants without NEC. Further study is needed to determine the predictive value of fecal BSs in the development of NEC.
| S-EPMC5207698 | biostudies-literature