lactoferrin and Retinopathy-of-Prematurity

This study aimed to systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants.. Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results.. Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36-0.86;. Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence.

Topics: Administration, Oral; Age of Onset; Bronchopulmonary Dysplasia; Cause of Death; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lactoferrin; Mycoses; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis

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.. 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 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 later.. We used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.. In our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates.. We used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence.. Meta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical RR 0.82, 95% CI 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06, -0.02; NNTB 25, 95% CI 17 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38, 95% CI, -4.67, -0.09; 3 studies, 1079 participants, low-certainty evidence). Sensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis with enteral lactoferrin supplementation (typical RR 0.87, 95% CI, 0.78, 0.97; typical RD -0.03, 95% CI, -0.05, -0.0; 9 studies, 4702 participants, low-certainty evidence). There were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86, 1.41; typical RD -0.00, 95% CI, -0.02, 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69, 1.17; typical RD -0.00, 95% CI, -0.01, 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence). Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty 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; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence). Lactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies.. We found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.

Topics: Administration, Oral; Bacterial Infections; Cause of Death; Chronic Disease; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lacticaseibacillus rhamnosus; Lactoferrin; Lung Diseases; Mycoses; Numbers Needed To Treat; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis

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.. Primary 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.. Randomized controlled trials (RCTs) evaluating oral lactoferrin at any dose or duration to prevent sepsis or NEC in preterm neonates.. Review authors used standard methods of the CNRG.. This 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.. Evidence 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.

Topics: Administration, Oral; Bacterial Infections; Cause of Death; Chronic Disease; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lacticaseibacillus rhamnosus; Lactoferrin; Lung Diseases; Mycoses; Numbers Needed To Treat; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis