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T Cells in Preterm Infants and the Influence of Milk Diet.
Sproat, T, Payne, RP, Embleton, ND, Berrington, J, Hambleton, S
Frontiers in immunology. 2020;:1035
Abstract
Preterm infants born before 32 weeks gestational age (GA) have high rates of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) despite recent improvements in infection control and nutrition. Breast milk has a clear protective effect against both these outcomes likely due to multiple mechanisms which are not fully understood but may involve effects on both the infant's immune system and the developing gut microbiota. Congregating at the interface between the mucosal barrier and the microbiota, innate and adaptive T lymphocytes (T cells) participate in this interaction but few studies have explored their development after preterm delivery. We conducted a literature review of T cell development that focuses on fetal development, postnatal maturation and the influence of milk diet. The majority of circulating T cells in the preterm infant display a naïve phenotype but are still able to initiate functional responses similar to those seen in term infants. T cells from preterm infants display a skew toward a T-helper 2(Th2) phenotype and have an increased population of regulatory cells (Tregs). There are significant gaps in knowledge in this area, particularly in regards to innate-like T cells, but work is emerging: transcriptomics and mass cytometry are currently being used to map out T cell development, whilst microbiomic approaches may help improve understanding of events at mucosal surfaces. A rapid rise in organoid models will allow robust exploration of host-microbe interactions and may support the development of interventions that modulate T-cell responses for improved infant health.
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Preterm neonatal immunology at the intestinal interface.
Van Belkum, M, Mendoza Alvarez, L, Neu, J
Cellular and molecular life sciences : CMLS. 2020;(7):1209-1227
Abstract
Fetal and neonatal development represents a critical window for setting a path toward health throughout life. In this review, we focus on intestinal immunity, how it develops, and its implications for subsequent neonatal diseases. We discuss maternal nutritional and environmental exposures that dictate outcomes for the developing fetus. Although still controversial, there is evidence in support of an in utero microbiome. Specific well-intentioned and routine applications of antibiotics, steroids, and surgical interventions implemented before, during, and after birth skew the neonate towards pro-inflammatory dysbiosis. Shortly after birth, a consortium of maternal and environmentally derived bacteria, through cross-talk with the developing host immune system, takes center stage in developing or disrupting immune homeostasis at the intestinal interface. We also examine subsequent immunological cross-talks, which involve neonatal myeloid and lymphoid responses, and their potential impacts on health and disease such as necrotizing enterocolitis and sepsis, especially critical disease entities for the infant born preterm.
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Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk.
Hård, AL, Nilsson, AK, Lund, AM, Hansen-Pupp, I, Smith, LEH, Hellström, A
Acta paediatrica (Oslo, Norway : 1992). 2019;(6):998-1007
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Abstract
AIM: This nonsystematic review examined differences in the composition of raw maternal breastmilk and pasteurised donor milk and possible health effects on preterm infants. METHODS We searched PubMed up to July 2018 for studies published in English that focused on four comparisons as follows: raw maternal milk versus donor milk, human milk before and after Holder pasteurisation, milk from mothers who delivered preterm and at term and milk collected during early and late lactation. We also searched for possible effects of the milk components, as well as the effects of maternal and donor milk on preterm infants' health. RESULTS Raw maternal milk contained factors involved in antioxidant and anti-inflammatory defence, gut microbiome establishment and the maturation of immune defences, food tolerability and metabolism. Many of these factors were reduced or abolished in processed donor milk. Both maternal milk and donor milk have been associated with a reduced incidence of necrotising enterocolitis. High-dose feeding with maternal milk during the neonatal period reportedly reduced the risk of other morbidities and promoted growth and neurodevelopment. CONCLUSION Many of the components in raw maternal breastmilk were lacking in pasteurised donor milk, which was inferior in promoting the growth and development of very preterm infants.
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Effect of different doses of vitamin D supplementation on preterm infants - an updated meta-analysis.
Yang, Y, Li, Z, Yan, G, Jie, Q, Rui, 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. 2018;(22):3065-3074
Abstract
OBJECTIVE Vitamin D deficiency (VDD) is common among infants, especially in preterm babies. There are some controversies over its use on body development, immune function and incidence of bronchopulmonary dysplasia (BPD). METHODS We systematically reviewed PubMed, Embase, and Cochrane databases for studies in English, and in Wanfang, VIP, and Cnki databases for Chinese studies (databases were last launched on 1 August 2016). RESULTS Twelve original random controlled studies (seven in English and five in Chinese) were included (1). There are no differences between high-dose (800-1000 IU/d) and low-dose (400 IU/d) groups on calcium, phosphorus, and 25(OH)D concentrations (p > .05). However, length gain and head circumference gain are significantly increased in the high-dose group (p < .05) (2). IL-2, Ig-A, and Ig-G levels are significant increased in the vitamin D supplementation group compared with the control group (p < .05) (3). With respect to BPD, there is no significant difference between the vitamin D supplementation group and the control group (p > .05). CONCLUSIONS In preterm infants, daily supplementation of vitamin D in doses of 800-1000 IU compared with 400 IU appears to be better not only in development but also in immune function. But clinical trials with a larger sample size are still needed.
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Oropharyngeal Colostrum Administration in Very Low Birth Weight Infants: A Randomized Controlled Trial.
Zhang, Y, Ji, F, Hu, X, Cao, Y, Latour, JM
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2017;(9):869-875
Abstract
OBJECTIVES Studies have confirmed the safety of oropharyngeal administration of colostrum in very low birth weight infants. However, the effect of oropharyngeal administration of colostrum on immune system is inconclusive. This study aims to evaluate the effect of oropharyngeal administration of colostrum on secretory immunoglobulin A and lactoferrin in very low birth weight infants. DESIGN Randomized controlled trial. SETTING Forty-bedded neonatal ICU in a university children's hospital in the People's Republic of China. PATIENTS Very low birth weight infants were allocated to the study group (n = 32) and control group (n = 32). INTERVENTION The intervention was oropharyngeal administration of 0.2 mL of their mother's colostrum every 4 hours for 7 days. The control group received saline solution. MEASUREMENTS AND MAIN RESULTS Secretory immunoglobulin A and lactoferrin in urine and saliva were measured within 24 hours of life (baseline) and at 7 and 21 days. Primary outcomes were changes of secretory immunoglobulin A and lactoferrin in urine and saliva between baseline and at 7 and 21 days. Infant's clinical data were also collected during hospitalization. Change from baseline in lactoferrin in saliva at 7 days (5.18 ± 7.07 vs -1.74 ± 4.67 µg/mL; p < 0.001) and 21 days (5.31 ± 9.74 vs -1.17 ± 10.38 µg/mL; p = 0.02) shows statistic difference. No differences were found of lactoferrin in urine and also no differences of secretory immunoglobulin A in urine and saliva. There were also no differences between days to full enteral feeding, occurrence rate of clinical sepsis, proven sepsis, and necrotizing enterocolitis. CONCLUSIONS Oropharyngeal administration of colostrum can increases the level of lactoferrin in saliva in very low birth weight infants. No effect could be documented of secretory immunoglobulin A and lactoferrin in urine. Larger trials are needed to better describe the benefit of oropharyngeal administration of colostrum, if any, in very low birth weight infants.
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Medically Graded Honey Supplementation Formula to Preterm Infants as a Prebiotic: A Randomized Controlled Trial.
Aly, H, Said, RN, Wali, IE, Elwakkad, A, Soliman, Y, Awad, AR, Shawky, MA, Alam, MSA, Mohamed, MA
Journal of pediatric gastroenterology and nutrition. 2017;(6):966-970
Abstract
OBJECTIVES The aim of the study was to assess the effect of medically graded enteral honey supplementation on the intestinal microbiota, immune response, and somatic growth of preterm infants. METHODS A prospective randomized controlled trial was conducted on preterm infants with gestational age ≤34 weeks and postnatal age >3 days. After reaching 1/2 goal enteral feeds, medically graded bee honey was added to milk at a dose of 5, 10, 15, and 0 g/day for 2 weeks in groups A, B, C, and D, respectively. Anthropometric measurements, CD4 and CD8 cytokines, stool cultures, and stool polymerase chain reaction assays for molecular detection of microbiomes were performed at 0, 7, and 14 days of intervention. Analysis of variance test was used to detect differences among the 4 groups. RESULTS A total of 40 subjects were enrolled; 10 in each arm of the study. Compared with group D, all 3 intervention groups demonstrated significant increase in weight (P < 0.0001). Head circumference increased in groups B and C (P = 0.0056). There were no changes in CD4 or CD8 cytokines (P = 0.24 and P = 0.11, respectively). Enterobacter stool colonization decreased in groups A and B (P = 0.002), whereas Bifidobacterium bifidum colony counts increased in groups A, B, and C (P = 0.002) and lactobacilli colony counts increased in group B (P < 0.0001). Applying real-time polymerase chain reaction, B bifidum and lactobacilli increased in group C (P < 0.0001). CONCLUSIONS Supplementation of milk formula with medically graded honey was associated with changes in physical growth and colonic microbiota of preterm infants. Further studies are needed to examine the sustainability of these effects and associated long-term outcomes.