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Oropharyngeal Colostrum Positively Modulates the Inflammatory Response in Preterm Neonates.
Martín-Álvarez, E, Diaz-Castro, J, Peña-Caballero, M, Serrano-López, L, Moreno-Fernández, J, Sánchez-Martínez, B, Martín-Peregrina, F, Alonso-Moya, M, Maldonado-Lozano, J, Hurtado-Suazo, JA, et al
Nutrients. 2020;(2)
Abstract
During the first days of life, premature infants have physiological difficulties swallowing, thereby missing out on the benefits of breastfeeding. The aim of this study is to assess the effects of oropharyngeal mother's milk administration in the inflammatory signaling of extremely premature infants. Neonates (n = 100) (<32 week's gestation and/or <1500 g) were divided into two groups: mother's milk group (n = 48), receiving 0.2 mL of oropharyngeal mother's milk every 4 h for the first 15 days of life, and a control group (n = 52), not receiving oropharyngeal mother's milk. Serum concentrations of interleukin (IL) IL-6, IL-8, IL-10, IL-1ra, tumor necrosis factor alpha (TNF-α), and interferón gamma (IFN-γ) were assessed at 1, 3, 15, and 30 days of postnatal life. Maternal and neonatal outcomes were collected. The rate of common neonatal morbidities in both groups was similar. The mother's milk group achieved full enteral feeding earlier, and showed a decrease in Il-6 on days 15 and 30, in IL-8 on day 30, and in TNF-α and INF-γ on day 15, as well as an increase in IL-1ra on days 3 and 15 and in IL-10 on day 30. Oropharyngeal mother's milk administration for 15 days decreases the pro-inflammatory state of preterm neonates and provides full enteral nutrition earlier, which could have a positive influence on the development of the immune system and inflammatory response, thereby positively influencing other developmental outcomes.
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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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Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis.
He, Y, Cao, L, Yu, J
Medicine. 2018;(35):e11976
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Abstract
BACKGROUND Currently, prophylactic use of drugs to promote a healthy gut microbiota and immune system in preterm infants is hot debated, among which lactoferrin is a promising supplementation. However, the effect and safety of lactoferrin to prevent late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants remains controversial. METHODS Databases including Medline, Ovid-Embase, The Cochrane Library, CBM, CNKI, and VIP database of Chinese Journal were searched to collect randomized controlled trials (RCTs) about lactoferrin for preventing LOS and NEC in preterm infants. Languages of included RCTs were restricted to English and Chinese. Meta-analysis was conducted by Rev Man 5.3 software. The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS A total of 9 RCTs, involving 1834 patients, were included. Pooled analysis showed that prophylactic lactoferrin could significantly reduce the incidence all culture-proven LOS (41/629 [6.5%] vs 96/659 [15.3%]; RR 0.47; 95% CI 0.33-0.67; P < .01) and NEC (stage II or more) (9/448 [2.0%] vs 26/462 [5.6%]; RR 0.40; 95% CI 0.18-0.86; P < .01). Lactoferrin was also associated with a significantly decreased hospital-acquired infection (16/139 [11.5%] vs 35/140 [25%]; RR 0.47; 95% CI 0.27-0.80; P < .01); and infection-related mortality (4/474 [0.8%] vs 25/505 [4.9%]; RR 0.24; 95% CI 0.04-1.32; P < .01, I = 53%). Lactoferrin could shorten time to reach full enteral feeding (weighted mean difference [WMD] = -2.11, 95% CI -3.12 to -1.10; P < .01) and showed a decreasing trend of duration of hospitalization (WMD = -1.69, 95% CI -6.87 to 3.50; P < .01; I = 95%). Lactoferrin did not have a significant effect on all-cause mortality (22/625 [3.5%] vs 35/647 [5.4%]; RR 0.70; 95% CI 0.38-1.30; P = .16; I = 13%). None of the included trials reported any confirmed adverse effects caused by the supplemented lactoferrin or probiotics. CONCLUSION Current evidence indicates that lactoferrin could significantly reduce the incidence of NEC and LOS, and decrease the risk of hospital-acquired infection and infection-related mortality in premature infants without obvious adverse effects.
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Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants.
Cortez, J, Makker, K, Kraemer, DF, Neu, J, Sharma, R, Hudak, ML
Journal of perinatology : official journal of the California Perinatal Association. 2018;(1):71-74
Abstract
OBJECTIVE Human milk (donor milk (DM) and/or maternal milk (MM)) feedings protect against late onset sepsis (LOS), necrotizing enterocolitis (NEC) and death. However, DM lacks many anti-infective components of MM. Therefore, we studied exclusive MM feedings to evaluate the full effect of human milk on infectious and other outcomes in premature infants. STUDY DESIGN All infants born before 33 weeks postmenstrual age (PMA) who received exclusive (>95%) MM or exclusive preterm formula (PF) were included in this prospective investigation. RESULTS Sixty-three infants (53%) received MM and 55 infants (47%) received PF. Both groups had similar baseline characteristics. Infants in the MM group achieved full enteral nutrition sooner (14±8 vs 19±15 days, P<0.03) and required a shorter duration of central venous lines (14±10 vs 22±21, P<0.005). Fewer infants in the MM group developed LOS (9 vs 19, P<0.05) and pneumonia (8 vs 16, P<0.05) than PF infants. Only one MM and five PF infants developed NEC (Bell stage ⩾II). Logistic regression analysis using PMA and prolonged rupture of membranes as covariates demonstrated an increased rate of NEC (odds ratio=8.85, CI=1.01 to 25.17, P=0.048) in PF infants. Periventricular leukomalacia (PVL) was more common in PF (4 vs 0, P=0.04) than in MM infants. CONCLUSION Feedings of MM advanced more rapidly and were associated with fewer infections than PF. A possible protective effect of MM against PVL, not previously described, may be related to its immune and anti-inflammatory components.
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[Research progress of the application of probiotics in preterm infants].
Gan, X, Li, J
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2016;(9):909-914
Abstract
The gastrointestinal structure, function and immunity of preterm infants are immature. Furthermore the gastrointestinal microbe colonization is abnormal. Therefore the preterm infants are prone to a variety of gastrointestinal diseases. Probiotics can regulate gastrointestinal microbe constitute, improve gastrointestinal barrier function, reduce gastrointestinal inflammation response and regulate the immunity. At present, it is used for the prevention of necrotizing enterocolitis, late-onset sepsis, and feeding intolerance. The safety and efficacy of probiotics for preterm infants are still controversial.
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Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells.
Akin, IM, Atasay, B, Dogu, F, Okulu, E, Arsan, S, Karatas, HD, Ikinciogullari, A, Turmen, T
American journal of perinatology. 2014;(12):1111-20
Abstract
OBJECTIVE Lactoferrin (LF) is effective in the prevention of sepsis in very low birth weight (VLBW) neonates. T-regulatory cells (Tregs) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis. The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis (NEC) in premature infants and to evaluate the possible effects of LF on Treg levels. STUDY DESIGN In this prospective, placebo-controlled, double-blind, randomized trial, infants either VLBW or born before 32 weeks were assigned to receive either placebo (n = 25), or 200 mg LF (n = 25) daily throughout hospitalization. Episodes of culture proven nosocomial sepsis and NEC were recorded. The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge. A third comparison was made with healthy term neonates (n = 16). RESULTS Fewer sepsis episodes were observed in LF-treated infants (4.4 vs. 17.3/1,000 patient days, p = 0.007) with none developing NEC, without statistical significance. Treg levels at birth and discharge were similar, while preterm infants showed significantly lower levels than term controls. However, individual increases in Treg levels were higher in the LF group. CONCLUSION LF prophylaxis reduced nosocomial sepsis episodes. Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed. Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis.
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Probiotics in the prevention of necrotizing enterocolitis.
Ganguli, K, Walker, WA
Journal of clinical gastroenterology. 2011;:S133-8
Abstract
Necrotizing enterocolitis (NEC) is a common gastrointestinal inflammatory necrosis affecting almost exclusively premature infants usually after oral nutrition has been started, for example, 10 day plus postpartum. Although the pathogenesis is incompletely understood, major risk factors include prematurity and incomplete bacterial colonization. Evidence has been shown that the premature infant because of rapid passage through the birth canal or because of delivery by cesarean section has an inadequate initial ingestion of maternal colonic and vaginal flora and therefore, an inadequate initial colonization with less diversity of bacteria phylla and fewer species of bacteria in the microbiota. As a result, they are more susceptible to environmental pathogens. In addition, prematures have immature intestinal defenses (glycocalyx, tight junctions, innate immune response, etc.) resulting in excessive inflammation in response to luminal stimuli. Recently, we reported that genes mediating the innate inflammatory immune response are developmentally expressed with an increase in toll-like receptors, signaling molecules and transgenic factors and decreased negative regulators of inflammation, which undoubtedly contribute to an excessive inflammatory response. Several clinical studies have suggested that the use of probiotics and ingestion of expressed maternal breast milk containing probiotics can help to stabilize colonization and to reduce the incidence and severity of NEC when given to premature infants at risk. Meta-analyses of multiple small studies strongly suggest a protective effect in the use of probiotics. A multicenter study in Taiwan suggests that Bifidobacteria infantis and Lactobacillus acidophilus in combination may prevent NEC. These meta-analyses suggest that these probiotics should be used in routine care of premature infants. Other clinicians, however, suggest caution, holding out for a single protocol multicenter trial before routine use can be suggested.