Parent and Provider Perspectives on the Imprecise Label of "Human Milk Fortifier" in the NICU.

In the critical care of preterm infants, feeding is complex and potentially harmful to an immature gastrointestinal system. Parents have expressed the desire to be fully informed about what is being fed to their child, as this places them in the best position to nurture their child's health. In the parent-engaged setting of the Necrotizing Enterocolitis Symposium, NICU parents expressed concern and confusion about how cow's milk product and donor human milk product both carry the label "Human Milk Fortifier" (HMF). Accordingly, two online surveys were developed to characterize how the label HMF is used and interpreted in the NICU by parents and providers. Of 774 United States participants, only 21.9% of providers reported consistently describing the source of HMF to parents, and only 20.6% of parents whose child received an HMF product report knowing the source. Parents expressed that they were "not given information" regarding HMF, while both parents and healthcare providers expressed that "the label (HMF) is misleading". This study documents the ambiguity around the label HMF as well as the need for more specific language and clearer communication.

Evaluation of parenteral nutrition-associated liver disease in surgical infants for necrotizing enterocolitis.

The purpose of this study was to determine the factors associated with parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC) and followed up the postoperative outcomes for long term parenteral nutrition (PN).This study included a retrospective review of 87 infants with NEC and managed surgically from July 2007 to May 2017 at the Children's Hospital, Chongqing Medical University. Clinical data and procedure information were collected and analyzed.Among the infants included, 16.1% of patients developed PNALD. Multivariable logistic regression analysis revealed progressive clinical deterioration (OR, 5.47; 95% CI, 1.10-26.96; P = .037) was independent risk factor for PNALD whereas congenital heart disease (OR, 0.068; 95% CI, 0.008-0.55; P = .012) presentation served as a protective factor.The current data suggested the distinct disease process for cardiac patients with NEC, which might help in the prevention and treatment of PNALD for patients with NEC.

Team-Based Implementation of an Exclusive Human Milk Diet.

BACKGROUND: The University of Virginia neonatal intensive care unit is a 51-bed unit with approximately 600 to 700 admissions per year. Despite evidenced-based clinical care, necrotizing enterocolitis (NEC) and feeding intolerance remained problematic. PURPOSE: In September 2016, the neonatal intensive care unit implemented an exclusive human milk diet (EHMD) for infants born 1250 g or less with the goal of reducing NEC, feeding intolerance, parenteral nutrition use, and late-onset sepsis. Length of stay, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity were also evaluated. METHODS: A work group developed systems for charging and documenting products used in an EHMD. Outcomes were compared with a control group of similar infants born prior to the availability of the EHMD. RESULTS: Infants who received an EHMD had significantly fewer late-onset sepsis evaluations (P = .0027) and less BPD (P = .018). While not statistically significant, less surgical NEC was also demonstrated (4 cases vs 1 case, which was 57% of total NEC cases vs 14.3%) while maintaining desirable weight gain and meeting financial goals. IMPLICATIONS FOR PRACTICE: A multidisciplinary team that implements financial and documentation systems can provide a sustainable clinical practice that improves patient outcomes. Ongoing evaluations of clinical and financial data provide valuable information to guide future clinical practices related to the EHMD. IMPLICATIONS FOR RESEARCH: Future research on the anti-inflammatory effect of an EHMD is needed to provide direction regarding a potential dose-dependent response for reduced BPD rates and severity. The role of human milk and prevention or mitigation of sepsis is not fully understood, but the reduction of the number of late-onset sepsis evaluations may support the relationship between an EHMD and infection protection. Exploring clinical and financial outcomes for implementing the EHMD in infants born more than 1250 g remains a key area for research.

Early enteral feeding in preterm infants.

Early enteral feeding is a potentially modifiable risk factor for necrotising enterocolitis (NEC) and late onset sepsis (LOS), however enteral feeding practices for preterm infants are highly variable. High-quality evidence is increasingly available to guide early feeding in preterm infants. Meta-analyses of randomised trials indicate that early trophic feeding within 48 h after birth and introduction of progressive enteral feeding before 4 days of life at an advancement rate above 24 ml/kg/day can be achieved in clinically stable very preterm and very low birthweight (VLBW) infants, without higher mortality or incidence of NEC. This finding may not be generalisable to high risk infants such as those born small for gestational age (SGA) or following absent/reversed end diastolic flow velocity (AREDFV) detected antenatally on placental Doppler studies, due to the small number of such infants in existing trials. Trials targeting such high-risk preterm infants have demonstrated that progressive enteral feeding started in the first 4 days is safe and does not lead to higher NEC or mortality; however, there is a paucity of data to guide feeding advancement in such infants. There is little trial evidence to support bolus or continuous gavage feeding as being superior in clinically stable preterm infants. Trials that examine enteral feeding are commonly unblinded for technical and practical reasons, which increases the risk of bias in such trials, specifically when considering potentially subjective outcome such as NEC and LOS; future clinical trials should focus on objective, primary outcome measures such as all-cause mortality, long term growth and neurodevelopment. Alternatively, important short-term outcomes such as NEC could be used with blinded assessment.

Solely human milk diets for preterm infants.

Human milk provides not only ideal nutrition for infant development but also immunologic factors to protect from infection and inflammation. For the newborn preterm infant, the natural delivery of milk is not attainable, and instead pumped maternal milk, donor human milk, and human milk fortification are mainstays of clinical care. Current research demonstrates a decreased risk of necrotizing enterocolitis with maternal milk and donor human milk when individually compared to formula and with a complete human milk diet of maternal milk supplemented with donor human milk. The incidence of severe retinopathy of prematurity is decreased with an exclusive human milk diet, and this decrease is more pronounced with human milk-based compared to bovine milk-based human milk fortifier. The incidence of other morbidities such as late-onset sepsis and bronchopulmonary dysplasia is decreased with higher dose of human milk though significant differences are not apparent in exclusive human milk diet studies.

Probiotics and Human Milk Oligosaccharides in Premature Infants.

Intestinal dysbiosis precedes and is a likely causative factor in necrotizing enterocolitis (NEC) and many cases of late-onset sepsis. Randomized controlled trials and observational cohort studies demonstrate decreased risk of NEC, sepsis, and death with the administration of probiotic microbes and decreased risk of NEC and sepsis with feeding of human milk. Animal studies suggest promising mechanisms by which probiotic microbes and human milk oligosaccharides alter the composition of the intestinal microbiota and may prevent disease in premature infants. Inclusion of parents in discussions of the risks and benefits of human milk and probiotics for premature infants is essential.

The Role of Probiotics in the Prevention of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a frequent and severe life-threatening disease affecting the gastrointestinal tract of preterm infants. Given that NEC occurs in a well-defined population of patients, there might be a considerable benefit in identifying specific pharmacological and nutritional preventive strategies, that could reduce the incidence of NEC. Amongst nutritional strategies emphasis has been put on the use of probiotics. Therefore, the aim of this review is to summarize currently available evidence on the role of probiotics in general, as well as the role of specific probiotic strains or their combinations, in the prevention of NEC.

Effect of probiotics on C-reactive protein levels in preterm infants: Secondary analysis of a randomized controlled trial.

BACKGROUND: Excessive inflammation is associated with adverse outcomes in preterm infants. C- reactive protein (CRP) is a marker of inflammation/infection. Probiotics have anti-inflammatory properties. Randomized controlled trials (RCTs) in preterm infants have not reported effect of probiotics on CRP. AIM: To evaluate effect of probiotics on CRP in preterm infants who had participated in a RCT of Bifidobacterium breve (B. breve) m-16v. METHODS: Data on all infants (GA <33 weeks, n = 159) enrolled in the RCT was analyzed. For study purpose, CRP <15 mg/L and ≤10 mg/L was considered normal for the first week, and thereafter respectively. Mixed logistic regression modelling was used to assess probiotic effect on CRP levels. RESULTS: There were 1579 CRP measurements (Probiotic: 851 vs. Placebo: 728). Baseline characteristics and number [Median (IQR)] of CRP estimations per infant [l0 (5, 20) vs. 10 (6, 17), p = 0.861] were comparable between probiotic vs. placebo group. There was no significant difference in the proportion of infants with high CRP over time (treatment by weekly time points interaction, p = 0.187), and across all time points between probiotic and placebo group (adjusted OR: 1.62, 95% CI: 0.91-2.88, p = 0.102)CONCLUSION:B. breve m-16v did not decrease CRP levels in preterm infants born <33 weeks.

Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates - a review of current evidences.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most common acute and fatal gastrointestinal emergency in very low birth weight (VLBW) preterm neonates with mortality range from 15 to 30%. NEC is likely due to multifactorial process such as oxidative injury, ischemic necrosis, and over-reactive inflammatory response to intestinal microbes. AIMS: To evaluate the role of amino acid supplementation for reduction of neonatal NEC in preterm neonates. METHOD: The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other database. RESULTS: This review included 15 RCTs that fulfilled inclusion criteria. The total neonates enrolled in these different RCT are 3424 (amino acid group 1711 and control 1713). Almost all participating neonates were of VLBW or extremely low birth weight (ELBW). In two trials, birth weight was between 1500-2000 grams. The intervention was started within first few days after birth and continued up to 30th day of postnatal age in most of the trials. In two trials, intervention was continued up to 120th day of postnatal age. Arginine, glutamine and N-acetyl cysteine (NAC) were used at the dose of 1.5 mol/kg/day (261 mg/kg/day), 0.3 grams/kg/day and 16-32 mg/kg/day, respectively. CONCLUSION: Role of amino acid in the prevention of neonatal NEC is not exclusively supported by the current evidence. Only three studies were able to show reduction in the incidence of NEC with amino acid supplementation (arginine, glutamine), and the remaining studies did not report any positive effect. Amino acid supplementation was not associated with significant reduction in mortality due to any causes. However, arginine supplementation was associated with significant reduction in mortality due to NEC. Two studies on glutamine were reported significant reduction in the incidence of invasive infection. Only one study reported significant positive effects on growth parameters and less time to reach full enteral feeds. None of the studies showed any effect on the duration of hospital stay.

Variabilidad en las prácticas sobre alimentación enteral del prematuro entre hospitales españoles de la red SEN-1500 / Variability in enteral feeding practices of preterm infants among hospitals in the SEN1500 Spanish neonatal network

Introducción: La nutrición adecuada es uno de los objetivos primordiales en el manejo de los recién nacidos prematuros. Sin embargo, la falta de evidencia en cuanto a cuál es la mejor estrategia para alcanzar este objetivo da lugar a que exista una gran variabilidad en las prácticas de alimentación. Esta variabilidad podría estar relacionada con las diferencias que existen en la incidencia de complicaciones como la enterocolitis necrosante (ECN). Objetivo: Valorar la variabilidad en las prácticas sobre alimentación entre las unidades neonatales de la red SEN-1500. Método: Estudio transversal, mediante cuestionario, solicitando información sobre alimentación del recién nacido de muy bajo peso (RNMBP) (leche donada, momento de inicio, trófica, incrementos, fortificantes, probióticos) en el año 2013. Resultados: Contestaron 60/98 hospitales; la tasa de respuesta fue mayor en centros con más de 50 RNMBP/año (30/31). El 67% tienen protocolo de alimentación, el 52% refieren variabilidad en su unidad y el 25% disponen de leche donada. Se inicia la alimentación en las primeras 48 h, aunque se retrasa en las edades más bajas aun en ausencia de fallo hemodinámico. Además de la inestabilidad hemodinámica hay otras situaciones por las que se demora su inicio (ausencia de leche materna, CIR, flujo umbilical alterado, asfixia), mientras que raramente se retrasa por ausencia de meconio o por mantener un catéter umbilical. Por debajo de 25 semanas la mitad comienzan directamente con incrementos progresivos en lugar de nutrición trófica. Los incrementos raramente alcanzan 30 ml/kg/día. Casi todos usan fortificantes y vitaminas. El uso de probióticos es excepcional. Conclusiones: Existe gran variabilidad en la política de alimentación del RNMBP entre las unidades neonatales españolas. Aunque algunas diferencias en las prácticas de alimentación están justificadas por la falta de evidencia, hay intervenciones que sí han demostrado su eficacia, como disponer de un protocolo de alimentación (basado en pruebas) o tener acceso a leche donada; su implementación en todos los centros podría disminuir la incidencia de ECN y mejorar el estado nutricional de los RNMBP (AU)

Introduction: Proper nutrition is one of the primary objectives in the management of preterm infants. However, lack of evidence on the best strategy to achieve this objective has led to a great variability in feeding practices. This variability may be related to the differences in the incidence of complications, such as necrotising enterocolitis (NEC). Objective: The aim of this study is to assess the variability in clinical practice regarding enteral feeding in SEN-1500 Spanish network. Method: An observational study was conducted using a questionnaire sent out in 2013 requesting information about feeding very low birth weight (VLBW) neonates (bank milk, start time, trophic feeding, increases, fortifiers and probiotics). Results: Responses were received from 60 of the 98 hospitals. The response rate was higher in centres with more than 50VLBW/year (30/31). Just over two-thirds (67%) have feeding protocols, and 52% refer to variability within their unit. A milk bank is available in 25% of the units. First feeding occurs fairly evenly throughout first 48hours, although it is delayed in lower gestational ages, even when there is no haemodynamic failure. In addition to hemodynamic instability there are other situations when the start is delayed (absence of breast milk, CIR, altered umbilical flow, asphyxia), while it is rarely delayed by absence of meconium or maintain an umbilical catheter.Half of those under 25 weeks begin directly with progressive increases instead of trophic feeding. Increases rarely reach 30ml/kg/day. Almost all use fortification and vitamins. There was a significant use of probiotics at the time of the survey. Conclusions: There is great variability in enteral nutrition policies in VLBW in Spain. Although some differences are justified by the lack of evidence, there are other interventions that have proven to be effective, such as evidence-based protocols or access to donor milk. Implementation in all the units could reduce the incidence of NEC and improve the nutritional status (AU)

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. METHODS: Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. RESULTS: A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). CONCLUSION: Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

Standardized slow enteral feeding protocol reduces necrotizing enterocolitis in micropremies.

BACKGROUND: Compared to early enteral feeds, delayed introduction and slow enteral feeding advancement to reduce necrotizing enterocolitis (NEC) is not well studied in micropremies (<750g birth weight). METHODS: Pre-post case control study. Micropremies who followed a standardized slow enteral feeding (SSEF) protocol (September 2009 to March 2015) were compared with a similar group of historical controls (PreSSEF, January 2003 to July 2009). Enteral feeding withheld for first 10-14 days and advanced at <10 ml/kg/day in the SSEF group. RESULTS: Ninety-two infants in the SSEF group were compared with 129 PreSSEF group. Birth weight and gestational age in SSEF and PreSSEF were similar. Breast milk initiation rate was higher in SSEF (87.0 vs. 72.0%, p = 0.01) compared to PreSSEF, but were similar at full enteral feeds. Compared with PreSSEF, feeding initiation day, full enteral feeding day, parenteral nutrition days, and total central line days were longer in SSEF. There was significant reduction in NEC (1.1 vs. 16.2%, p < 0.01), surgical NEC (0.0 vs. 7.8%, p < 0.01) and NEC/death (7.6 vs. 29.5%, p < 0.01), in SSEF compared to PreSSEF. SSEF, compared to PreSSEF, had more cholestasis (41.8 vs 28.8%, p = 0.04), higher peak serum alkaline phosphatase (638 vs. 534 IU/dL, p < 0.01), but similar rates of late-onset sepsis (39.1 vs 43.4%, p = 0.53). In infants who survived to discharge, SSEF had higher discharge weight, lower extra-uterine growth restriction, and similar length of stay, compared to PreSSEF. CONCLUSIONS: A SSEF protocol significantly reduces the incidence of NEC and combined NEC/death in micropremies.

Human milk is the feeding strategy to prevent necrotizing enterocolitis!

Human milk is the preferred diet for preterm infants as it protects against a multitude of NICU challenges, specifically necrotizing enterocolitis. Infants who receive greater than 50% of mother's own milk (MOM) in the 2 weeks after birth have a significantly decreased risk of NEC. An additional factor in the recent declining rates of NEC is the increased utilization of donor human milk (DHM). This creates a bridge until MOM is readily available, thus decreasing the exposure to cow milk protein. Preterm infants are susceptible to NEC due to the immaturity of their gastrointestinal and immune systems. An exclusive human milk diet compensates for these immature systems in many ways such as lowering gastric pH, enhancing intestinal motility, decreasing epithelial permeability, and altering the composition of bacterial flora. Ideally, preterm infants should be fed human milk and avoid bovine protein. A diet consisting of human milk-based human milk fortifier is one way to provide the additional nutritional supplements necessary for adequate growth while receiving the protective benefits of a human milk diet.

Impact of probiotics on necrotizing enterocolitis.

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention.

Asociaciones de probióticos para la prevención de la enterocolitis necrosante y la reducción de la sepsis tardía y la mortalidad neonatal en recién nacidos pretérmino de menos de 1500g: Una revisión sistemática / 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

INTRODUCCIÓN: Los recién nacidos pretérminos y de muy bajo peso presentan mayor riesgo de enterocolitis necrosante (NEC) dado que su colonización a nivel intestinal se produce más tardíamente y es diferente respecto a los recién nacidos a término, además de presentar con mayor frecuencia otros factores favorecedores como isquemia intestinal. Se cree que los probióticos pueden modificar la microbiota y la respuesta immune de los recién nacidos, disminuyendo la incidencia de NEC. OBJETIVO: Revisar los estudios realizados con diferentes probióticos y comparar diferentes combinaciones de éstos para ver si es beneficiosa su administración de forma rutinaria en recién nacidos pretérmino de menos de 1500g para evitar la enterocolitis necrosante, reducir la sepsis tardía y la mortalidad. Material y MÉTODOS: Se llevó a cabo una revisión sistemática entre enero 1980 y marzo 2014, en MEDLINE, EMBASE y Cochrane Central Register of Controlled Trials. Se seleccionaron los estudios clínicos con recién nacidos prematuros de <1500g y/o <34 semanas descartando aquellos con puntuaciones de Jadad menores de 4. RESULTADOS: Se seleccionaron 9 estudios, de 24 pre-seleccionados, con un total de 3521 recién nacidos. Se observó que los probióticos reducen la incidencia de NEC (RR 0,39; 95% CI: 0,26-0,57) y la mortalidad (RR 0,70; 95% CI: 0,52-0,93). No se detectaron diferencias significativas con el placebo en la disminución de sepsis tardía (RR 0,91; 95% CI: 0,78-1,96). Finalmente, cuando se analizan las distintas cepas, la combinación de 2 probióticos (Lactobacillus acidophiluscon Bifidobacterium bifidum) demostró reducir la mortalidad de forma significativa comparada con otras combinaciones de probióticos (RR 0,32; 95% CI: 0,15-0,66, NNT 20; 95% CI: 12-50). CONCLUSIONES: Los probióticos son beneficiosos en cuanto a la prevención de NEC y reducen la mortalidad en pretérminos de menos de 1.500g. Además, la combinación de dos probióticos (Lactobacillus acidophilus con Bifidobacterium bifidum) presenta mayor beneficio. Dada la diferencia de composición de probióticos son necesarios estudios aleatorizados comparando diferentes combinaciones de probióticos

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 1500g. 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 <1500g or <34 weeks were selected, discarding those with Jadad scores lower than 4. 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

Minimal short-term effect of dietary 2'-fucosyllactose on bacterial colonisation, intestinal function and necrotising enterocolitis in preterm pigs.

Human milk decreases the risk of necrotising enterocolitis (NEC), a severe gastrointestinal disease that occurs in 5-10 % of preterm infants. The prebiotic and immune-modulatory effects of milk oligosaccharides may contribute to this protection. Preterm pigs were used to test whether infant formula enriched with α1,2-fucosyllactose (2'-FL, the most abundant oligosaccharide in human milk) would benefit gut microbial colonisation and NEC resistance after preterm birth. Caesarean-delivered preterm pigs were fed formula (Controls, n 17) or formula with 5 g/l 2'-FL (2'-FL, n 16) for 5 d; eight 2'-FL pigs (50 %) and twelve Controls (71 %) developed NEC, with no difference in lesion scores (P=0·35); 2'-FL pigs tended to have less anaerobic bacteria in caecal contents (P=0·22), but no difference in gut microbiota between groups were observed by fluorescence in situ hybridisation and 454 pyrosequencing. Abundant α1,2-fucose was detected in the intestine with no difference between groups, and intestinal structure (villus height, permeability) and digestive function (hexose absorption, brush border enzyme activities) were not affected by 2'-FL. Formula enrichment with 2'-FL does not affect gut microbiology, digestive function or NEC sensitivity in pigs within the first few days after preterm birth. Milk 2'-FL may not be critical in the immediate postnatal period of preterm neonates when gut colonisation and intestinal immunity are still immature.

Probiotics for prevention of necrotizing enterocolitis and sepsis in preterm infants.

PURPOSE OF REVIEW: Few areas in neonatal medicine have generated as much discussion and controversy as the use of prophylactic probiotics for the prevention of necrotizing enterocolitis. We summarize recent studies from the last 1-2 years. RECENT FINDINGS: Systematic reviews show that probiotics reduce the risk of necrotizing enterocolitis but there are methodological limitations to all the published trials, and the largest trial to date is at odds with the conclusions of the meta-analyses. Trials have used a range of commercially available products with differing species, and administered these at different times to heterogeneous populations of preterm babies. Although there is strong evidence to show that 'probiotics' are likely to represent a major advance for neonatal care, it is increasingly clear that not all species have beneficial effects in preterm infants. This makes interpretation of meta-analyses complex, and the determination of a single 'risk reduction' potentially flawed. SUMMARY: Despite current uncertainties, it is difficult for clinicians to ignore the current data, and increasing numbers now use commercially available products. It remains a matter of concern that many products lack the robust quality control most clinicians and parents would consider important for use in vulnerable populations. Head-to-head trials are needed.

Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet.

OBJECTIVE: Human milk is the best form of nutrition for preterm infants and has been associated with a lower incidence of necrotizing enterocolitis (NEC). Infants that develop NEC have a higher incidence of feeding intolerance and longer hospitalizations. The combination of a donor milk bank and donor milk-derived fortifier has changed feeding practices in neonatal intensive care units (NICU). The purpose of this study is to assess the benefits and cost of an exclusive human milk (EHM) diet in very low birth weight (VLBW) infants in a community level III NICU. STUDY DESIGN: This is a retrospective study including preterm infants ⩽28 weeks and/or VLBW (⩽1500 g) who were enrolled from March 2009 until March 2014. Infants were grouped as follows: group H (entirely human milk based, born March 2012 to 2014), group B (bovine-based fortifier and maternal milk, born March 2009 to 2012), group M (mixed combination of maternal milk, bovine-based fortifier and formula, born March 2009 to 2012) and group F (formula fed infants, born March 2009 to 2012). Baseline characteristics among the four groups were similar. RESULT: The study included 293 infants between gestational ages 23 to 34 weeks and birth weights between 490 and 1700 g. Feeding intolerance occurred less often (P<0.0001), number of days to full feeds was lower (P<0.001), incidence of NEC was lower (P<0.011), and total hospitalization costs were lower by up to $106,968 per infant (P<0.004) in those fed an EHM diet compared with the other groups. Average weight gain per day was similar among the four groups (18.5 to 20.6 g per day). CONCLUSIONS: Implementing an EHM diet in our VLBW infants has led to a significant decrease in the incidence of NEC. Other benefits of this diet include: decreased feeding intolerance, shorter time to full feeds, shorter length of stay, and lower hospital and physician charges for extremely premature and VLBW infants.

A retrospective analysis of the effect of human milk on prevention of necrotizing enterocolitis and postnatal growth.

OBJECTIVE: The objective of this study is to determine whether the use of donor human milk (DHM) in very low birth weight (VLBW, ⩽1500 g) neonates in a large neonatal intensive care unit (NICU) affected the rate of necrotizing enterocolitis (NEC) or impacted growth. STUDY DESIGN: This was a retrospective chart review of 550 VLBW neonates following the introduction of DHM as the preferred diet if maternal breast milk (MBM) was not available. Demographics, growth parameters, incidence of NEC or death and days of DHM or MBM were extracted from charts. RESULT: Compared with infants who received human milk (HM) on fewer than 50% of hospital days, neonates who received HM on ⩾50% of hospital days had equivalent growth outcomes but lower rates of NEC (NEC 3.4 vs 13.5%, P<0.001) and mortality (1.0 vs 4.2%, P=0.017). Growth and NEC rates were inversely correlated with the duration of exposure to HM. CONCLUSION: HM should always be the diet of choice in preterm infants. DHM is a safe alternative, if MBM is not available. Although the use of HM is associated with lower rates of NEC, growth rates were significantly lower in infants with significant HM intake. The decline in growth rates following the introduction of DHM should draw attention to optimize fortification of all HM feedings.

Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis.

The nature and role of the intestinal leukocytes in necrotizing enterocolitis (NEC), a severe disease affecting premature infants, remain unknown. We now show that the intestine in mouse and human NEC is rich in lymphocytes that are required for NEC development, as recombination activating gene 1­deficient (Rag1­/­) mice were protected from NEC and transfer of intestinal lymphocytes from NEC mice into naive mice induced intestinal inflammation. The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term human and mouse intestine, is required for lymphocyte influx through TLR4-mediated upregulation of CCR9/CCL25 signaling. TLR4 also mediates a STAT3-dependent polarization toward increased proinflammatory CD3+CD4+IL-17+ and reduced tolerogenic Foxp3+ Treg lymphocytes (Tregs). Th17 lymphocytes were required for NEC development, as inhibition of STAT3 or IL-17 receptor signaling attenuated NEC in mice, while IL-17 release impaired enterocyte tight junctions, increased enterocyte apoptosis, and reduced enterocyte proliferation, leading to NEC. Importantly, TLR4-dependent Th17 polarization could be reversed by the enteral administration of retinoic acid, which induced Tregs and decreased NEC severity. These findings identify an important role for proinflammatory lymphocytes in NEC development via intestinal epithelial TLR4 that could be reversed through dietary modification.