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Effects of prebiotics on sepsis, necrotizing enterocolitis, mortality, feeding intolerance, time to full enteral feeding, length of hospital stay, and stool frequency in preterm infants: a meta-analysis.
Chi, C, Buys, N, Li, C, Sun, J, Yin, C
European journal of clinical nutrition. 2019;(5):657-670
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Abstract
BACKGROUND/OBJECTIVES Prebiotics are increasingly recognized as an effective measure to promote health and prevent adverse health outcomes in preterm infants. We aimed to systematically review the randomized controlled trials (RCTs) in this area. SUBJECTS/METHODS Relevant studies from January 2000 to June 2018 were searched and selected from PubMed, Medline, Scopus, and the Cochrane Library. RCTs were included if they involved preterm infant participants, included a prebiotic intervention group, measured incidence of sepsis, feeding intolerance, mortality, time to full enteral feeding, necrotizing enterocolitis (NEC), length of hospital stay, and stool frequency as outcomes. RESULTS Eighteen RCTs (n = 1322) were included in the final meta-analysis. Participants who took prebiotics showed significant decreases in the incidence of sepsis (with a risk ratio (RR) of 0.64, 95% CI: 0.51, 0.78), mortality (RR = 0.58. 95% CI: 0.36, 0.94), length of hospital stay (mean difference (MD): -5.18, 95% CI: -8.94, -1.11), and time to full enteral feeding (MD: -0.99, 95% CI: -1.15, 0.83). The pooled effects showed no significant differences between intervention and control groups in relation to the morbidity rate of NEC (RR = 0.79, 95% CI: 0.44, 1.44) or feeding intolerance (RR = 0.87, 95% CI: 0.52, 1.45). CONCLUSIONS The results showed that the use of prebiotics with preterm infants is safe and can decrease the incidence of sepsis, mortality, length of hospital stay, and time to full enteral feeding but not NEC.
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Time to Full Enteral Feeding for Very Low-Birth-Weight Infants Varies Markedly Among Hospitals Worldwide But May Not Be Associated With Incidence of Necrotizing Enterocolitis: The NEOMUNE-NeoNutriNet Cohort Study.
de Waard, M, Li, Y, Zhu, Y, Ayede, AI, Berrington, J, Bloomfield, FH, Busari, OO, Cormack, BE, Embleton, ND, van Goudoever, JB, et al
JPEN. Journal of parenteral and enteral nutrition. 2019;(5):658-667
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Abstract
BACKGROUND Transition to enteral feeding is difficult for very low-birth-weight (VLBW; ≤1500 g) infants, and optimal nutrition is important for clinical outcomes. METHOD Data on feeding practices and short-term clinical outcomes (growth, necrotizing enterocolitis [NEC], mortality) in VLBW infants were collected from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2947). Specifically, 5 NICUs in Guangdong province in China (GD), mainly using formula feeding and slow feeding advancement (n = 1366), were compared with the remaining NICUs (non-GD, n = 1581, Oceania, Europe, United States, Taiwan, Africa) using mainly human milk with faster advancement rates. RESULTS Across NICUs, large differences were observed for time to reach full enteral feeding (TFF; 8-33 days), weight gain (5.0-14.6 g/kg/day), ∆z-scores (-0.54 to -1.64), incidence of NEC (1%-13%), and mortality (1%-18%). Adjusted for gestational age, GD units had longer TFF (26 vs 11 days), lower weight gain (8.7 vs 10.9 g/kg/day), and more days on antibiotics (17 vs 11 days; all P < .001) than non-GD units, but NEC incidence and mortality were similar. CONCLUSION Feeding practices for VLBW infants vary markedly around the world. Use of formula and long TFF in South China was associated with more use of antibiotics and slower weight gain, but apparently not with more NEC or higher mortality. Both infant- and hospital-related factors influence feeding practices for preterm infants. Multicenter, randomized controlled trials are required to identify the optimal feeding strategy during the first weeks of life.
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Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial.
Adhisivam, B, Kohat, D, Tanigasalam, V, Bhat, V, Plakkal, N, Palanivel, C
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(19):3232-3237
Abstract
Objective: To compare the effect of fortified pasteurized donor human milk (PDHM) versus unfortified PDHM on the incidence of necrotizing enterocolitis (NEC) and immediate outcome among preterm neonates. Methods: This randomized controlled trial (RCT) conducted in a tertiary care teaching hospital, south India included 80 healthy preterm neonates randomized to two groups (Group A and B). Neonates in Group A and B were fed with fortified PDHM and unfortified PDHM, respectively. Neonates in both groups were managed uniformly as per standard NICU protocol. The primary outcome was the incidence of NEC and the secondary outcomes included severity of NEC, incidence of sepsis, mortality, duration of hospital stay, number of days to reach full enteral feeds and weight gain. Neonates were followed up for 28 days or discharge whichever was earlier. Results: The baseline maternal and neonatal characteristics in both groups were comparable. There was no increase in incidence of NEC in fortified PDHM group compared to unfortified PDHM group (2.5 versus 7.5%, p = .31). Severity of NEC, incidence of sepsis, mortality, duration of hospital stay, number of days to reach full enteral feeds and weight gain were also similar in both groups. Conclusions: Standard fortification of PDHM does not increase the incidence of NEC among preterm neonates.
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Human Milk and Infants With Congenital Heart Disease: A Summary of Current Literature Supporting the Provision of Human Milk and Breastfeeding.
Davis, JA, Spatz, DL
Advances in neonatal care : official journal of the National Association of Neonatal Nurses. 2019;(3):212-218
Abstract
BACKGROUND Human milk is a life-saving medical intervention. Infants with congenital heart disease are at an increased risk for necrotizing enterocolitis, chylothorax, feeding difficulties, and growth failure. In the absence of evidence-based care, their mothers are also at risk for low milk supply and/or poor breastfeeding outcomes. PURPOSE Summarize the role of human milk and clinical outcomes for infants with congenital heart disease (CHD). Summarize methods of ideal breastfeeding support. METHODS/SEARCH STRATEGY PubMed, Cochrane Library, and CINAHL were the databases used. The terms used for the search related to CHD and necrotizing enterocolitis were "human milk" and "necrotizing enterocolitis" and "congenital heart disease." This resulted in a total of 17 publications for review. FINDINGS Infants receiving exclusive human milk diet are at a lower risk for necrotizing enterocolitis and will have improved weight gain. Infants with chylothorax who receive skimmed human milk have higher weight-for-age scores than formula-fed infants. Maternal breastfeeding education correlates with decreased risk of poor breastfeeding outcomes. IMPLICATIONS FOR PRACTICE Human milk is the ideal source of nutrition for infants with CHD and should be encouraged by the care team. Evidence-based lactation education and care must be provided to mothers and families prenatally and continue throughout the infant's hospitalization. If a mother's goal is to directly breastfeed, this should be facilitated during the infant's hospital stay. IMPLICATIONS FOR RESEARCH Evaluate the role between human milk and the incidence of necrotizing enterocolitis, feeding difficulties, and clinical outcomes in the population of infants with CHD.
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The WHEAT pilot trial-WithHolding Enteral feeds Around packed red cell Transfusion to prevent necrotising enterocolitis in preterm neonates: a multicentre, electronic patient record (EPR), randomised controlled point-of-care pilot trial.
Gale, C, Modi, N, Jawad, S, Culshaw, L, Dorling, J, Bowler, U, Forster, A, King, A, McLeish, J, Linsell, L, et al
BMJ open. 2019;(9):e033543
Abstract
INTRODUCTION Necrotising enterocolitis (NEC) is a potentially devastating neonatal disease. A temporal association between red cell transfusion and NEC is well described. Observational data suggest that withholding enteral feeds around red cell transfusions may reduce the risk of NEC but this has not been tested in randomised trials; current UK practice varies. Prevention of NEC is a research priority but no appropriately powered trials have addressed this question. The use of a simplified opt-out consent model and embedding trial processes within existing electronic patient record (EPR) systems provide opportunities to increase trial efficiency and recruitment. METHODS AND ANALYSIS We will undertake a randomised, controlled, multicentre, unblinded, pilot trial comparing two care pathways: continuing milk feeds (before, during and after red cell transfusions) and withholding milk feeds (for 4 hours before, during and for 4 hours after red cell transfusions), with infants randomly assigned with equal probability. We will use opt-out consent. A nested qualitative study will explore parent and health professional views. Infants will be eligible if born at <30+0 gestational weeks+days. Primary feasibility outcomes will be rate of recruitment, opt-out, retention, compliance, data completeness and data accuracy; clinical outcomes will include mortality and NEC. The trial will recruit in two neonatal networks in England for 9 months. Data collection will continue until all infants have reached 40+0 corrected gestational weeks or neonatal discharge. Participant identification and recruitment, randomisation and all trial data collection will be embedded within existing neonatal EPR systems (BadgerNet and BadgerEPR); outcome data will be extracted from routinely recorded data held in the National Neonatal Research Database. ETHICS AND DISSEMINATION This study holds Research Ethics Committee approval to use an opt-out approach to consent. Results will inform future EPR-embedded and data-enabled trials and will be disseminated through conferences, publications and parent-centred information. TRIAL REGISTRATION NUMBER ISRCTN registry ISRCTN62501859; Pre-results.
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Necrotizing Enterocolitis and the Preterm Infant Microbiome.
Baranowski, JR, Claud, EC
Advances in experimental medicine and biology. 2019;:25-36
Abstract
Bacterial colonization patterns in preterm infants differ from those of their term counterparts due to maternal microbial diversity, delivery mode, feeding methods, antibiotic use, and exposure to commensal microbiota and pathogens in the neonatal intensive care unit (NICU). Early gut microbiome dysbiosis predisposes neonates to necrotizing enterocolitis (NEC), a devastating intestinal disease with high morbidity and mortality. Though mechanisms of NEC pathogenesis are not fully understood, the microbiome is a promising therapy target for prevention and treatment. Direct administration of probiotics to preterm infants has been shown to reduce the incidence of NEC, but is not without risk. The immature immune systems of preterm infants leave them vulnerable to even beneficial bacteria. Further research is required to investigate both short-term and long-term effects of probiotic administration to preterm infants. Other methods of altering the preterm infant microbiome must also be considered, including breastfeeding, prebiotics, and targeting the maternal microbiome.
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A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis.
Nolan, LS, Parks, OB, Good, M
Nutrients. 2019;(1)
Abstract
Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant's gestational and chronological age, lactation stage, and the mother and infant's health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC). Breast milk is a known protective factor in the prevention of NEC when compared with feeding with commercial formula. Breast milk supplements infants with human milk oligosaccharides, leukocytes, cytokines, nitric oxide, and growth factors that attenuate inflammatory responses and provide immunological defenses to reduce the incidence of NEC. This article aims to review the variety of immunomodulating components in breast milk that protect the infant from the development of NEC.
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Closing the Gap Between Recommended and Actual Human Milk Use for Fragile Infants: What Will It Take to Overcome Disparities?
Gephart, SM, Newnam, KM
Clinics in perinatology. 2019;(1):39-50
Abstract
This article describes the components of human milk and their value to reduce risk for necrotizing enterocolitis, disparities in access to human milk, potential relationships to care practices within the neonatal intensive care unit, and ways to overcome the disparity.
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Necrotizing Enterocolitis Pathophysiology: How Microbiome Data Alter Our Understanding.
Kim, CS, Claud, EC
Clinics in perinatology. 2019;(1):29-38
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Abstract
Necrotizing enterocolitis is a major cause of mortality and morbidity in the preterm infant population. The gut microbiome is of particular interest in research surrounding necrotizing enterocolitis, because variations in the intestinal microbiota seem to correlate with the risk of inflammation and disease. Recent advances in non-culture-based genomic sequencing have also allowed for more intricate analyses of the intestinal microbiome. Its evolution seems to be influenced by intrauterine and extrauterine factors, ranging from antenatal antibiotic exposure to type of enteral feeds. Ultimately, these alterations in the gut microbiome have the potential to result in devastating diseases like necrotizing enterocolitis.
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Increased risk of rickets but not fractures during childhood and adolescence following necrotizing enterocolitis among children born preterm in Sweden.
Magnusson, A, Ahle, M, Andersson, RE, Swolin-Eide, D, Elfvin, A
Pediatric research. 2019;(1):100-106
Abstract
BACKGROUND The aim was to clarify whether children born preterm with a history of necrotizing enterocolitis (NEC) had an increased risk of rickets, fractures, and/or vitamin D deficiency during childhood and adolescence compared to controls without NEC, matched for gestational age. METHODS All infants born in Sweden between 1987 and 2009 with a gestational age <32 + 0 weeks and a diagnosis of NEC were identified. Totally, 465 children with a history of NEC and 2127 controls were included. International Classification of Diseases codes for all categories of fractures, rickets, vitamin D deficiency, and malnutrition were analyzed. RESULTS In total, 94 of the 465 children with NEC died within 28 days. Of the 2127 controls, 288 died within 28 days. Among the remaining 371 NEC cases, 39 fracture occasions were identified. The 1839 controls had 204 fracture occasions. There was no significant difference in fractures. Rickets was diagnosed in 11 (3%) of the children with a history of NEC compared to 21 (1%) of the controls (odds ratio 2.65, 95% CI 1.26-5.53, p = 0.007). CONCLUSIONS This study showed an increased risk of rickets but not fractures during childhood and adolescence in children born preterm and with a history of NEC, compared to matched controls.