RCT to analyse efficacy of double port extension tubing connection to peripheral IV cannula in prevention of neonatal late onset sepsis

Late onset sepsis (LOS) and central-line associated blood stream infection (CLA-BSI) contribute toward the mortality and morbidity in prematurely born infants. The aim of this study is to investigate the effects of hospital-wide and unit-based interventions on LOS and CLA-BSI in infants born at <32 weeks gestation. Intensive care, high dependency days and catheter days were obtained from the unit database and blood culture results from a microbiology laboratory database. Poisson regression was used to evaluate the effects of interventions on LOS and CLA-BSI. Quarterly rates of LOS reduced from 26.1 to 2.9 per 1000 intensive care, high dependency days and CLA-BSI from 31.6 to 4.3 per 1000 catheter days between 2007 and 2012. Appointment of a hospital specialist vascular device nurse, a change in the mode of administration of vancomycin, standardization of the hospital skin and hub disinfection policy and the introduction of a venous infusion phlebitis scoring system were associated with a reduction of LOS to 55% (95% confidence interval: 40-74%) and CLA-BSI 45% (95% confidence interval: 33-61%) of pre-intervention levels. The standardization of the neonatal unit policy for skin disinfection and a move to a new building were associated with reductions of LOS to 64% (47-87%) and 54% (34-88%), respectively, and aseptic no touch technique for infusion access with CLA-BSI to 53% (37-75%) of pre-intervention levels. A multifaceted approach involving changes in antimicrobial and skin disinfection policy, training for aseptic no touch technique and surveillance resulted in sustained reduction in LOS and CLA-BSI rates.

Background: Neonatal sepsis is one of the most common causes of neonatal morbidity and mortality. Selenium has antioxidant and immune-modulating properties. Aim: The aim of this systematic review is to evaluate role of selenium supplementation in the prevention of late onset sepsis (LOS) among very low birth weight (VLBW) neonates. Methods: We searched literature for this review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) electronic PubMed, Embase, and Google Scholar. We also searched for ongoing clinical trials. Results: This review included two randomized controlled trials (RCTs) that fulfilled inclusion criteria. There was statistically significant reduction in the incidence of LOS in the intervention group [23.7 versus 35.6%; relative risk (RR) 0.67; 95% CI 0.52–0.86; p= .001; number needed to treat (NNT) 8.4; 95% CI 5.2–20.96]. However, mortality due to any cause prior to hospital discharge was not statistically significant in between the groups (6.1% intervention group versus 6.9% control group; RR 0.88; 95% CI 0.49–1.61; p= .68). Conclusions: Evidences from current systematic review revealed that selenium supplementation has some role in the prevention of LOS. However, due to limited evidences and heterogeneity between studies, large RCTs are recommended among VLBW neonates.

Background Lactoferrin (LTF) is a promising drug in the prevention of late-onset sepsis (LOS) in preterm infants as it causes priming of the immune system before the occurrence of insult. Aim The aim of this study is to evaluate the effect of LTF in the prevention of LOS. Participants and methods Preterm infants of gestational age less than or equal to 34 weeks showing no signs of sepsis in the first 72 h and admitted to NICU of Alexandria University Children Hospital from August 2019 to April 2020 were included in this study. Fifty six patients were randomly allocated into two groups: LTF group (n=28 patients) and control group (n=28 patients). Patients in the LTF group received LTF for 28 days postnatally or till 36 weeks postmenstrual age, whichever is reached first. All patients were monitored for development of LOS. Results Compared with the control group, LTF treatment was associated with a significantly lower incidence of culture-proven LOS (8/28 vs. 2/28, respectively) with a P value of 0.036. The administration of LTF decreased the serum C-reactive protein level at the end of the study in comparison with the level at the beginning of the study in the LTF group, with a mean value of 5.44±16.18 versus 3.71±2.57, respectively (P=0.021), and in comparison with the control group, with a mean value of 5.44±16.18 versus 27.45±55.20, respectively (P=0.021). Conclusion LTF reduces the incidence of culture-proven LOS in preterm neonates aged less than or equal to 34 weeks. LTF has been proven to have anti-inflammatory properties through its ability to decrease the C-reactive protein level.

Routine screening for colonization by Gram-negative bacteria in neonates at intensive care units for the prediction of sepsis: systematic review and meta-analysis

Background Late onset sepsis is a frequent complication of prematurity, associated with increased mortality and morbidity. Probiotics may prevent late onset sepsis in premature infants. The aim of this study was to determine prophylactic effect of oral probiotics in prevention of late onset sepsis of very preterm infants. Materials and Methods This study was a randomized, double blinded, placebo controlled trial. Eighty preterm infants born at 0.05). Conclusion According to the results, usage of prophylactic probiotics can reduce the incidence of late onset sepsis and its mortality. By consuming probiotics preterm infants could reach the full enteral feeding in a shorter period of time, but the duration of hospitalization not reduced.

Late onset sepsis (LOS) and Central line associated blood stream infection (CLA-BSI) remains a major cause of mortality and morbidity in preterm infants. Numerous interventions were introduced between 2007 and...

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect

Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC in preterm neonates. We used the search strategy of the Cochrane Neonatal Review Group (CNRG) including searches of CENTRAL (The Cochrane Library), MEDLINE and PREMEDLINE, EMBASE and CINAHL. We also searched trials registries and the conference proceedings of Pediatric Academic Society. Searches updated in July 2011. Randomized or quasi-randomized controlled trials evaluating oral lactoferrin at any dose or duration for the prophylaxis of sepsis or NEC in preterm neonates. Data collection and analysis were performed according to the standard methods of the CNRG. One trial (Manzoni 2008) that randomized 472 very low birth weight infants was eligible. A statistically significant reduction in late-onset sepsis was observed in the groups that received either lactoferrin alone (RR 0.34, 95% CI 0.17 to 0.70) or in combination with Lactobacillus rhamnosus GG (RR 0.27, 95% CI 0.12 to 0.60).In subgroup analyses, infants weighing less than 1000 g and those fed exclusively on maternal milk had a significant reduction in late-onset sepsis after oral lactoferrin supplementation alone. In the group supplemented with oral lactoferrin and Lactobacillus rhamnosus, infants weighing less than 1000 g had a significant reduction in late-onset sepsis, a result not seen in infants fed maternal milk exclusively.Prophylaxis with oral lactoferrin alone did not reduce the incidence of NEC (RR 0.33, 95% CI 0.09 to 1.17), but a significant reduction in NEC with a combination of lactoferrin and Lactobacillus rhamnosus GG was noted (RR 0.05, 95% CI 0.00 to 0.90).No adverse effects due to lactoferrin were observed in this study. Long-term neurological outcomes were not assessed in this trial. Oral lactoferrin prophylaxis reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. There is no evidence of efficacy of oral lactoferrin (given alone) in the prevention of NEC in preterm neonates.Well designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and NEC. The effect of exclusive maternal milk feeding should be clarified.

Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC in preterm neonates. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE and PREMEDLINE (1966 to Oct 2009), EMBASE (1980 to Oct 2009) and CINAHL (1982 to Oct 2009) were searched. Ongoing trials at www.clinicaltrials.gov and www.controlled-trials.com were searched. Conference proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research and European Society for Pediatric Research) were searched for abstracts 1990 from the journal 'Pediatric Research' and 'Abstracts Online'. Randomized or quasi-randomized controlled trials evaluating oral lactoferrin at any dose or duration for the prophylaxis of sepsis or NEC in preterm neonates. Data collection and analysis were performed according to the standard methods of the CNRG. One trial (Manzoni 2008) that randomized 472 very low birth weight infants was eligible. A statistically significant reduction in late-onset sepsis was observed in the groups that received either lactoferrin alone (RR 0.34, 95% CI 0.17, 0.70; RD -0.11, 95% CI -0.18, -0.05; NNT 9, 95% CI 5, 20) or in combination with Lactobacillus rhamnosus GG (RR 0.27, 95% CI 0.12, 0.60; RD -0.13, 95% CI -0.19, -0.06; NNT 8, 95% CI 5, 17).In subgroup analyses, infants weighing less than 1000 g and those fed exclusively on maternal milk had significant reduction in late-onset sepsis after oral lactoferrin supplementation alone. In the group supplemented with oral lactoferrin and Lactobacillus rhamnosus, infants weighing less than 1000 g had a significant reduction in late-onset sepsis, but not exclusively maternal milk fed infants.Prophylaxis with oral lactoferrin alone did not reduce the incidence of NEC (RR 0.33, 95% CI 0.09, 1.17; RD -0.04, 95% CI -0.08, 0.00), but a significant reduction in NEC with combination of lactoferrin with Lactobacillus rhamnosus GG was noted (RR 0.05, 95% CI 0.00, 0.90; RD -0.06, 95% CI -0.10, -0.02; NNT17, 95% CI 10, 50).No adverse effects due to lactoferrin were observed in this study. Long-term neurological outcomes were not assessed in this trial. Oral lactoferrin prophylaxis reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. There is no evidence of efficacy of oral lactoferrin (given alone) in the prevention of NEC in preterm neonates.Well designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and NEC. The effect of exclusive maternal milk feeding should be clarified.

Background: Oral application of mother's own milk (MOM) in very low birth weight (VLBW) neonates may provide an effective method of cleaning the oral cavity and influencing the immunocompetent cells there. Methods: A double-blind randomized controlled trial was conducted in a tertiary level neonatal unit on VLBW neonates; that is, neonates with birth weight <1,500 g, hospitalized within 72 hours of birth. The intervention was oral care with MOM. The primary objective was to observe the effect of oral care with MOM on late onset sepsis (LOS) and also on mortality, days to attain full enteral feed, necrotizing enterocolitis (NEC), exclusive breastfeeding rates at discharge, and total hospital stay (THS). Results: One hundred ten neonates were randomized to intervention and no-intervention group; 55 in each group. Neonates in the intervention group developed LOS in 9.1% versus 27.3% in no-intervention group (p = 0.013). Mortality was 9.1% versus 16.4% (p = 0.252); days to attain full enteral feeds were 6.94 ± 2.34 versus7.4 ± 2.31 days (p = 0.306); exclusive BF rates at discharge were 83% versus 75% (p = 0.449); THS was 30.72 ± 8.72 versus 33.5 ± 8.7 days (p = 0.267) in the two groups, respectively. There was no effect on NEC. Conclusion: Oral care of VLBW neonates with MOM reduces LOS and mortality.

Introduction: Lactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties. Objectives: The 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. Methods: A 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. Results: Two 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). Conclusion: Consumption 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.

Introduction: Late-onset Sepsis (LOS) causes significant morbidity and mortality in preterm infants. Probiotics have been suggested to improve the integrity of mucosal barrier by modifying the enteric microflora and suppress the overgrowth and translocation of pathogens in the gut, thus preventing life- threatening infections. Although probiotics have a definite role in prevention of Necrotising Enterocolitis (NEC) in preterm neonates, their effect on prevention of LOS in preterm neonates is still uncertain. Aim: To evaluate the role of probiotics in reducing incidence of LOS in preterm neonates (&lt;34 weeks). Materials and Methods: A double blinded randomised control trial was conducted in a tertiary care Neonatal Intensive Care Unit (NICU) in Karnataka, India between 1st January 2019 to 31st December 2019. Seventy haemodynamically stable preterm neonates, &lt;34 weeks of Gestational Age (GA), were randomised into ‘Probiotic’ and ‘Placebo’ groups. The probiotic group (n=36) was prophylactically administered Bacillus clausii suspension at a dose of 2.5 mL per-oral (0.4×109 spores in 1 mL) BD with breast milk, from initiation of enteral feeds till seven days, discharge/ death/LOS, whichever was earlier. The placebo group (n=34) received breast milk with sterile water 2.5 mL per- oral BD. All the neonates were investigated and managed as per standard hospital protocol. Primary outcome of the study was to find the incidence of LOS. Student’s t-test, Mann-Whitney U test, Chi-square test and Fisher’s exact test were used for statistical analysis. Results: There was no significant difference between the probiotic vs placebo group, with respect to incidence of LOS (11.11% vs 17.64%; (p&gt;0.05)) and duration of hospital stay (10.86±3.19 vs 11.23±2.98 days; (p&gt;0.05)). However, incidence of feed intolerance in the probiotic group (11.11%) was significantly less than that the other (26%) (p&lt;0.05). Conclusion: Probiotics, prophylactically fed enterally, did not reduce the incidence of LOS but provide a promising strategy to prevent feed intolerance in premature neonates.

Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams

Strategies to Limit Infections in the Neonate and to Reduce Infection-related Mortality

Lactoferrin and prevention of late-onset sepsis in the pre-term neonates