Reduction In Late-onset Sepsis Research Articles

Effectiveness of a probiotic combination on the neurodevelopment of the very premature infant

Probiotics have shown a benefit in reducing necrotising enterocolitis in the premature infant, however the study of their effect on premature neonates’ neurodevelopment is limited. The aim of our study was to elucidate whether the effect of Bifidobacterium bifidum NCDO 2203 combined with Lactobacillus acidophilus NCDO 1748 could positively impact the neurodevelopment of the preterm neonates. Quasi-experimental comparative study with a combined treatment of probiotics in premature infants < 32 weeks and < 1500 g birth weight, cared for at a level III neonatal unit. The probiotic combination was administered orally to neonates surviving beyond 7 days of life, until 34 weeks postmenstrual age or discharge. Globally, neurodevelopment was evaluated at 24 months corrected age. A total of 233 neonates were recruited, 109 in the probiotic group and 124 in the non-probiotic group. In those neonates receiving probiotics, there was a significant reduction in neurodevelopment impairment at 2 years of age RR 0.30 [0.16–0.58], and a reduction in the degree of impairment (normal-mild vs moderate-severe, RR 0.22 [0.07–0.73]). Additionally, there was a significant reduction in late-onset sepsis (RR 0.45 [0.21–0.99]). The prophylactic use of this probiotic combination contributed to improving neurodevelopmental outcome and reduced sepsis in neonates born at < 32 weeks and < 1500 g.

Interventions for reducing late-onset sepsis in neonates: an umbrella review.

Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period andincluding one or more RCTs reporting LOS. Two authorsindependently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC,chlorhexidine for skin or cord care, and kangaroo care for lowbirth weight babies. Similarly, moderate-quality evidenceshowed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. The overview summarizes the evidence fromthe Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.

Meta-Analysis of Enteral Lactoferrin Supplementation for Reducing the Risk of Preterm Infants Sepsis

Introduction: Severe COVID-19 in pregnancy is strongly associated with preterm infant late-onset sepsis (LOS), which is a major cause of morbidity and mortality in infants. Recently, Lactoferrin, an iron-binding protein significantly discovered in human colostrum, shows potential effect on reducing the risk of preterm infant LOS and mortality by its immunomodulatory properties. Therefore, this study aimed to evaluate the effect of Lactoferrin on reducing the risk of preterm LOS, necrotizing enterocolitis (NEC), and mortality in preterm infants. &#x0D; Methods: This study followed the guidelines provided by PRISMA. A literature search was conducted with PubMed, Cochrane Library, Google Scholar, and ScienceDirect. The combined effect of LOS, NEC and mortality incidence were presented as risk ratios (RR) with a 95% confidence interval (CI) using a random-effects model (REM) or fixed-effects model (FEM) forest plot. Furthermore, the heterogeneity level was checked by I2 and the p-value of the chi2 test.&#x0D; Results: The incidence of LOS was significantly higher in the control than lactoferrin supplementation group [RR=0.65, 95% CI (0.56,0.77), p&lt;0.00001, I2=56%]. However, there were no significant differences in NEC [RR=0.80, 95% CI (0.63,1.02), p=0.10, I2=39%] and mortality [RR=0.94, 95% CI (0.77,1.13), p=0.49, I2=39%], despite the trends are higher in the control group.&#x0D; Conclusion: This meta-analysis showed that enteral lactoferrin supplementation in preterm infants was associated with a significant reduction in LOS, but not NEC stage II or III and all-cause mortality.&#x0D; Registered Protocol: The protocol of this review was already registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42021279189.

Routine prefeed gastric aspiration in preterm infants: a systematic review and meta-analysis.

Despite lack of evidence, the practice of routine prefeed gastric residue aspiration before the next feed is common. Recent studies suggest that this practice might be even harmful. Therefore, we aimed to evaluate the effect of avoiding routine prefeed gastric residue aspiration as compared to routine aspiration, on various clinical outcomes in preterm infants. We searched five different electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library) until March 8, 2021. Only randomized controlled trials comparing the practice of routine prefeed gastric aspiration with no routine aspiration in preterm infants were considered eligible. The random-effects meta-analysis was done using RevMan 5.3 software. Of the 894 unique records identified by our search, we included 6 studies (451 participants) in the review. There was no significant difference in the incidence of necrotizing enterocolitis (RR 0.80; 95% CI 0.31 to 2.08; 421 participants in 5 trials). Avoiding routine prefeed aspiration was associated with achieving full enteral feeds earlier (MD - 3.19 days, 95% CI - 4.22 to - 2.16), shorter duration of hospitalization (MD - 5.32 days; 95% CI - 10.25 to - 0.38), and lower incidence of late-onset sepsis (RR 0.77; 95% CI 0.60 to 0.99). Time to regain birth weight, days of total parenteral nutrition or central venous line usage, culture-positive sepsis, and all-cause mortality did not differ between the two groups.Conclusion: In the absence of other signs of feed intolerance, routine prefeed gastric residue aspiration should be avoided in preterm infants.Prospero registration number: CRD42020197657 What is Known: • Though, routine prefeed aspiration before next feed is a common practice in preterm gavage-fed infants. • Recent study suggests that the omission of routine gastric residual evaluation led to improved weight gain and earlier hospital discharge. What is New: • Low- to moderate-quality evidence suggest that avoiding routine prefeed gastric residue monitoring helps in the reduction of late-onset sepsis, achieving full enteral feeds earlier, and earlier discharge from the hospital. • Abandoning the practice of routine prefeed aspiration in absence of other signs of feed intolerance in preterm low birthweight neonates is safe.

Temporal trends of care practices, morbidity, and mortality of extremely preterm infants over 10-years in South Wales, UK

Contemporary outcome data of preterm infants are essential to commission, evaluate and improve healthcare resources and outcomes while also assisting professionals and families in counselling and decision making. We analysed trends in clinical practice, morbidity, and mortality of extremely preterm infants over 10 years in South Wales, UK. This population-based study included live born infants < 28 weeks of gestation in tertiary neonatal units between 01/01/2007 and 31/12/2016. Patient characteristics, clinical practices, mortality, and morbidity were studied until death or discharge home. Temporal trends were examined by adjusted multivariable logistic regression models and expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). A sensitivity analysis was conducted after excluding infants born at < 24 weeks of gestation. In this population, overall mortality for infants after live birth was 28.2% (267/948). The odds of mortality (aOR 0.93, 95% CI [0.88, 0.99]) and admission to the neonatal unit (0.93 [0.87, 0.98]) significantly decreased over time. Non-invasive ventilation support during stabilisation at birth increased significantly (1.26 [1.15, 1.38]) with corresponding decrease in mechanical ventilation at birth (0.89 [0.81, 0.97]) and following admission (0.80 [0.68–0.96]). Medical treatment for patent ductus arteriosus significantly decreased over the study period (0.90 [0.85, 0.96]). The incidence of major neonatal morbidities remained stable, except for a reduction in late-onset sepsis (0.94 [0.89, 0.99]). Gestation and centre of birth were significant independent factors for several outcomes. The results from our sensitivity analysis were compatible with our main results with the notable exception of death after admission to NICU (0.95 [0.89, 1.01]). There were significant improvements in survival and reduction of late-onset sepsis of extreme preterm infants in South Wales between 2007 and 2016. The sensitivity analysis suggests that some of the temporal changes observed were driven by improved outcomes in the most preterm of infants. Clinical practices related to respiratory support have changed but significant variations in clinical practices and outcomes between centres remain unexplained. The adoption of regional evidence-based clinical guidelines is likely to improve outcomes and reduce variation.

ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions 1.

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95%CI = 0.86-1.04; p= 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon.

Enteral Lactoferrin Supplementation for Preventing Sepsis and Necrotizing Enterocolitis in Preterm Infants: A Meta‑Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

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.

Family integrated care in single family rooms for preterm infants and late-onset sepsis: a retrospective study and mediation analysis.

During hospital stay after birth, preterm infants are susceptible to late-onset sepsis (LOS). To study the effect of family integrated care in single family rooms (SFRs) compared to standard care in open bay units (OBUs) on LOS. Peripheral or central venous catheters (PVCs/CVCs) and parenteral nutrition (PN) were investigated as potential mediators. Secondary outcomes were length of stay, exclusive breastfeeding at discharge, and weight gain during hospital stay. Single-center retrospective before-after study with preterm infants admitted ≥3 days. We studied 1,046 infants (468 in SFRs, 578 in OBUs, median gestational age 35 weeks). SFRs were associated with less LOS (adjusted odds ratio (OR) 0.486, 95% confidence interval (CI): 0.293; 0.807, p = 0.005). PVCs (indirect effect -1.757, 95% CI: -2.738; -1.068), CVCs (indirect effect -1.002, 95% CI: -2.481; 0.092), and PN (indirect effect -1.784, 95% CI: -2.688; -1.114) were possible mediators of the effect. PN was the main mediator of the effect of SFRs on LOS. We found shorter length of stay (median length of stay in SFRs 10 days and in OBUs 12 days, adjusted β -0.088, 95% CI: -0.159; -0.016, p = 0.016), but no differences in weight gain or exclusive breastfeeding at discharge. SFRs were associated with decreased incidences of LOS and shorter length of hospital stay. The positive effect of SFRs on LOS was mainly mediated through a decreased use of PN in SFRs. Family integrated care (FICare) in single family rooms for preterm infants was associated with less late-onset sepsis events during hospital stay and a shorter length of hospital stay after birth. FICare in single family rooms was associated with less use of peripheral or central venous catheters and parenteral nutrition. Mediation analysis provided insights into the mechanisms underlying the effect of FICare in single family rooms on late-onset sepsis and helped explain the differences observed in late-onset sepsis between FICare in single family rooms and open bay units. The reduction in late-onset sepsis in FICare in single family rooms was mediated by a reduced use of intravenous catheters and parenteral nutrition.

Practice variations and rates of late onset sepsis and necrotizing enterocolitis in very preterm born infants, a review.

The burden of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) remains high for newborns in low- and high-income countries. Very preterm born infants born below 32 weeks gestation are at highest risk because their immune system is not yet adapted to ex-utero life, providing intensive care frequently compromises their skin or mucosa and they require a long duration of hospital stay. An epidemiological overview is difficult to provide because there is no mutually accepted definition available for either LOS or NEC. LOS incidence proportions are generally reported based on identified blood culture pathogens. However, discordance in minimum day of onset and whether coagulase negative staphylococci or fungi should be included into the reported proportions lead to variation in reported incidences. Complicating the comparison are the absence of biomarkers, ancillary lab tests or prediction models with sufficiently high positive and/or negative predictive values. The only high negative predictive values result from negative blood culture results with negative lab results allowing to discontinue antibiotic treatment. Similar difficulties exist in reporting and diagnosing NEC. Although most publications base their proportions on a modified version of Bell's stage 2 or 3, comparisons are made difficult by the multifactorial nature of the disease reflecting several pathways to intestinal necrosis, the absence of a reliable biomarker and the unclear differentiation from spontaneous intestinal perforations. Comparable reports in very low birthweight infants range between 5% and 30% for LOS and 1.6% to 7.1% for NEC. Evidence based guidelines to support treatment are missing. Treatment for LOS remains largely empirical and focused mainly on antibiotics. In the absence of a clear diagnosis, even unspecific early warning signals need to be met with antibiotic treatment. Cessation after negative blood culture is difficult unless the child was asymptomatic from the beginning. As a result, antibiotics are the most commonly prescribed medications, but unnecessary exposure may result in increased risk for mortality, NEC, further infections and childhood obesity or asthma. Finding ways to limit antibiotic use are thus important and have shown a large potential for improvement of care and limitation of cost. Over recent decades, none of the attempts to establish novel therapies have succeeded. LOS and NEC proportions remained mostly stable. During the past 10 years however, publications emerged reporting a reduction, sometimes by almost 50%. Most concern units participating in a surveillance system using quality improvement strategies to prevent LOS or NEC (e.g., hand hygiene, evidence based "bundles", feeding onset, providing own mother's milk). We conclude that these approaches display a potential for wider spread reduction of LOS and NEC and for a subsequently more successful development of novel therapies as these often address the same pathways as the prevention strategies.

Probiotics for preterm infants - time to end all controversies.

SummaryMortality, necrotising enterocolitis (NEC), late onset sepsis (LOS) and feeding intolerance are significant issues for very preterm (< 32 weeks) and extremely preterm (< 28 weeks) infants. The complications of ≥ Stage II NEC [e.g. Resection of the gangrenous gut, survival with intestinal failure, recurrent infections, prolonged hospital stay, and long‐term neurodevelopmental impairment (NDI)] impose a significant health burden. LOS also carries significant burden including long‐term NDI due to adverse effects of inflammation on the preterm brain during the critical phase of development. Frequent stopping of feeds due to feeding intolerance is a significant iatrogenic contributor to postnatal growth failure in extremely preterm infants. Over 25 systematic reviews and meta‐analyses of RCTs (~12 000 participants) have reported that probiotics significantly reduce the risk of all‐cause mortality, NEC ≥ Stage II, LOS and feeding intolerance in preterm infants. Systematic reviews and meta‐analysis of non‐RCTs have also shown that the benefits after adopting probiotics as a standard prophylaxis for preterm infants are similar to those reported in RCTs. No intervention comes close to probiotics when it comes to significant reduction in death, NEC, LOS and feeding intolerance at a cost of less than a dollar a day irrespective of the setting and baseline incidence of NEC. The common controversies that are preventing the rapid uptake of probiotics for preterm infants are addressed in this paper.

Clinical Outcomes Related to the Gastrointestinal Trophic Effects of Erythropoietin in Preterm Neonates: A Systematic Review and Meta-Analysis.

Erythropoietin (EPO) plays an important role in the development and maturation of the gastrointestinal tract. Recombinant EPO (rEPO) has been used to prevent anemia of prematurity. The gastrointestinal trophic effects of EPO may reduce feeding intolerance and necrotizing enterocolitis (NEC) in preterm neonates. The aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the effects of rEPO on clinical outcomes such as feeding intolerance, stage II or higher NEC, any stage NEC, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia in preterm neonates.Twenty-five RCTs (intravenous: 13; subcutaneous: 10; enteral: 2; n=4025) were eligible for inclusion. Meta-analysis of data from 17 RCTs (rEPO compared with placebo) with the use of a fixed-effects model showed no significant effect of rEPO on stage II or higher NEC (RR: 0.87; 95% CI: 0.64, 1.19; P=0.39). Meta-analysis of data from 25 RCTs (rEPO compared with placebo) showed that rEPO significantly decreased the risk of any stage NEC [cases/total sample: 120/2058 (5.83%) compared with 146/1967 (7.42%); RR: 0.77; 95% CI: 0.61, 0.97; P=0.03]. Only one RCT reported on time to full feedings. Meta-analysis of data from 15 RCTs showed a significant reduction in late-onset sepsis after rEPO administration (RR: 0.81; 95% CI: 0.71, 0.94; P=0.004). Meta-analysis of 13 RCTs showed no significant effect of rEPO on mortality, retinopathy of prematurity, and bronchopulmonary dysplasia. Prophylactic rEPO had no effect on stage II or higher NEC, but it reduced any stage NEC, probably by reducing feeding intolerance, which is often labeled as stage I NEC. Adequately powered RCTs are required to confirm these findings.

Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials.

Probiotic supplementation reduces the risk of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants, but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of bronchopulmonary dysplasia (BPD). Fifteen randomized controlled trials (4782 infants; probiotics: 2406) were included. None of the included studies assessed BPD as the primary outcome. Meta-analysis confirmed a significant reduction of NEC (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.33 to 0.81, p = 0.004; random effects model), and an almost significant reduction of LOS (RR 0.82, 95% CI 0.65 to 1.03, p = 0.084). In contrast, meta-analysis could not demonstrate a significant effect of probiotics on BPD, defined either as oxygen dependency at 28 days of life (RR 1.01, 95% CI 0.91 to 1.11, p = 0.900, 6 studies) or at 36 weeks of postmenstrual age (RR 1.07, 95% CI 0.96 to 1.20, p = 0.203, 12 studies). Meta-regression did not show any significant association between the RR for NEC or LOS and the RR for BPD. In conclusion, our results suggest that NEC and LOS prevention by probiotics does not affect the risk of developing BPD in preterm infants.

Probiotic associations in the prevention of necrotising enterocolitis and the reduction of late-onset sepsis and neonatal mortality in preterm infants under 1500g. A systematic review

Abstract Introduction Necrotising enterocolitis (NEC) is one of the most common and serious acquired bowel diseases a premature newborn can face. This meta-analysis was performed comparing different probiotic mixtures to ascertain their benefits as a routine tool for preventing necrotising enterocolitis and reducing late-onset sepsis and mortality in premature neonates of less than 1500 g. Methods A systematic review of randomised controlled trials, between January 1980 and March 2014, on MEDLINE, the Cochrane Central Register of Controlled Trials, together with EMBASE, was carried out. Studies with infants Results 9 studies were selected for further investigation, pooling a total of 3521 newborns. Probiotics were found to reduce the NEC incidence (RR 0.39; 95% CI: 0.26–0.57) and mortality (RR 0.70; 95% CI: 0.52–0.93), with no difference to placebo regarding late-onset sepsis (RR 0.91; 95% CI: 0.78–1.06). Finally, when analysing the different strands, the use of a 2-probiotic combination ( Lactobacillus acidophilus with Bifidobacterium bifidum) proved to be statistically significant in reducing all-cause mortality when compared to other probiotic combinations (RR 0.32; 95% CI: 0.15–0.66, NNT 20; 95% CI: 12–50). Conclusions Probiotics are a beneficial tool in the prevention of NEC and mortality in preterm neonates. Moreover, the combination of 2 probiotics ( L. acidophilus with B. bifidum ) seems to produce the greatest benefits. However, due to the differences in probiotic components and administration, it would be wise to perform a randomised controlled trial comparing different probiotic mixtures.

Prevention of Late Onset Sepsis and Central-line Associated Blood Stream Infection in Preterm Infants.

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.

Early-Onset Neutropenia in Small-for-Gestational-Age Infants

Early neutropenia is more common in small for gestational age (SGA) neonates (birth weight <10th percentile) than in appropriately grown neonates. However, several aspects of this variety of neutropenia are unknown, including the duration, kinetic mechanism, and outcomes. Using 10 years of multihospital records, we studied SGA neonates who, during the first week after birth, had neutrophil counts <1000/μL. This degree of neutropenia was more common in SGA neonates (6%, 207/3650) than in non-SGA matched controls (1%, 46/3650; P < .001). Neutrophil counts stayed below the lower reference interval for 7 days. Ratios of immature to total neutrophils were within the reference interval, suggesting reduced neutrophil production, not accelerated neutrophil use or destruction. Increased nucleated red cells at birth correlated with decreased neutrophils (P < .001). Neutropenia was not independently associated with maternal hypertensive disorders, over and above the effect of SGA. Of 201 neutropenic SGA neonates, 129 (64%) also had thrombocytopenia. Sixteen percent of neutropenic neonates were treated with recombinant granulocyte colony-stimulating factor (rG-CSF) or intravenous immunoglobulin (IVIG), with no reduction in late-onset sepsis or necrotizing enterocolitis (NEC). Regression analysis showed that neutropenia (but not thrombocytopenia in the absence of neutropenia) was independently associated with increased odds of developing necrotizing enterocolitis (odds ratio 4.01, 90% confidence interval 2.08 to 7.35, P < .001). Neutropenia of SGA is a condition of 1-week duration. It is more closely associated with SGA than maternal hypertension (likely owing to neutrophil hypoproduction associated with intrauterine hypoxia), often accompanied by thrombocytopenia, not obviously improved by rG-CSF or IVIG, and associated with an increased risk for NEC.

Lactoferrin and necrotizing enterocolitis

There is an intense interest among neonatal caregivers as to whether lactoferrin given enterally may reduce the incidence of necrotizing enterocolitis in preterm infants. This review presents scientific and clinical evidence that lactoferrin alleviates or prevents this life-threatening disease. Preclinical studies in neonatal rats showed that lactoferrin given orally before enteral infection with pathogenic Escherichia coli reduced bacteremia and mortality. A multicentered clinical trial found that very low-birth weight preterm infants given bovine lactoferrin had a significant reduction in late-onset sepsis; there was also a trend towards a diminished incidence of necrotizing enterocolitis. Although multicentered trials of lactoferrin use in preterm infants are near completion, regulatory burdens required to bring lactoferrin to the bedside may limit its availability. Extremely preterm infants should receive colostrum, a natural lactoferrin concentrate, immediately after birth and, ideally, continue on breast milk throughout the hospital stay. This practice appears well tolerated, but additional experience will tell us whether this practice reduces the prevalence of necrotizing enterocolitis.

Selenium and Vitamin A and E in the Nutrition of Very Low-Birth Weight Preterm Infants

Deficient antioxidant defenses in preterm infants have been implicated in diseases such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. The antioxidant properties of selenium, vitamin A, and vitamin E make these elements important in the nutrition of Very Low-Birth Weight (VLBW) infants. Selenium is a component of glutathione peroxidase, an enzyme that prevents the production of free radicals. The decrease in plasma selenium in VLBW infants in the first month after birth makes evident that preterm infants have low selenium store and require supplementation by parenteral and enteral nutrition. A meta-analysis, with only three trials, showed that selenium supplementation did not affect mortality, and the incidence of neonatal chronic lung disease or retinopathy of prematurity, but was associated with a reduction in lateonset sepsis. Most VLBW infants and extremely Low-Birth Weight Infants (ELBW) are born with low vitamin A stores and need vitamin A supplementation by intramuscular or enteral route. Low plasma retinol concentrations increase the risk of chronic lung disease/bronchopulmonary dysplasia and long-term respiratory disabilities in preterm infants. There is evidence that vitamin A supplementation decreases the mortality or oxygen requirement at one month of age, and oxygen requirement at 36 weeks’ postmenstrual age. Vitamin E blocks natural peroxidation of polyunsaturated fatty acids from lipid layers of cell membranes. VLBW infants have a decrease in plasma concentrations in the first month after birth suggesting the need of vitamin E supplementation. A meta-analysis on vitamin E supplementation concluded that vitamin E did not affect mortality, risk of bronchopulmonary dysplasia, and necrotizing enterocolitis but reduced the risk of intraventricular hemorrhage and increased the risk of sepsis. Serum vitamin E concentrations higher than 3.5 mg/dL are associated with a decrease in the risk of severe retinopathy of prematurity, and blindness, but also with an increase in neonatal sepsis. Caution is recommended with the supplementation of high doses of parenteral vitamin E and supplementation that increases serum levels above 3.5 mg/dL. In conclusion: although it is known that preterm infants are deficient in selenium, vitamin A and E, more studies are required to determine the best way to supplement and the impact of supplementation on neonatal outcome