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1.
The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review.
Nolan, LS, Rimer, JM, Good, M
Nutrients. 2020;(10)
Abstract
Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.
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2.
Impact of macronutrient supplements on later growth of children born preterm or small for gestational age: A systematic review and meta-analysis of randomised and quasirandomised controlled trials.
Lin, L, Amissah, E, Gamble, GD, Crowther, CA, Harding, JE
PLoS medicine. 2020;(5):e1003122
Abstract
BACKGROUND Nutritional supplements may improve short-term growth of infants born small (preterm or small for gestational age), but there are few data on long-term effects and concerns that body composition may be adversely affected. Effects also may differ between girls and boys. Our systematic review and meta-analysis assessed the effects of macronutrient supplements for infants born small on later growth. METHODS AND FINDINGS We searched OvidMedline, Embase, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews from inception to January 30, 2020, and controlled-trials.com, clinicaltrials.gov, and anzctr.org.au on January 30, 2020. Randomised or quasirandomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born small and growth was assessed after discharge. Primary outcome was body mass index (BMI) in childhood. Data were pooled using random-effect models. Outcomes were evaluated in toddlers (< 3 years), childhood (3 to 8 years), adolescence (9 to 18 years), and adulthood (>18 years). Forty randomised and 2 quasirandomised trials of variable methodological quality with 4,352 infants were included. Supplementation did not alter BMI in childhood (7 trials, 1,136 children; mean difference [MD] -0.10 kg/m2, [95% confidence interval (CI) -0.37 to 0.16], p = 0.45). In toddlers, supplementation increased weight (31 trials, 2,924 toddlers; MD 0.16 kg, [0.01 to 0.30], p = 0.03) and length/height (30 trials, 2,889 toddlers; MD 0.44 cm, [0.10 to 0.77], p = 0.01), but not head circumference (29 trials, 2,797 toddlers; MD 0.15 cm, [-0.03 to 0.33], p = 0.10). In childhood, there were no significant differences between groups in height (7 trials, 1,136 children; MD 0.22 cm, [-0.48 to 0.92], p = 0.54) or lean mass (3 trials, 354 children; MD -0.07 kg, [-0.98 to 0.85], p = 0.88), although supplemented children appeared to have higher fat mass (2 trials, 201 children; MD 0.79 kg, [0.19 to 1.38], p = 0.01). In adolescence, there were no significant differences between groups in BMI (2 trials, 216 adolescents; MD -0.48 kg/m2, [-2.05 to 1.08], p = 0.60), height (2 trials, 216 adolescents; MD -0.55 cm, [-2.95 to 1.86], p = 0.65), or fat mass (2 trials, 216 adolescents; MD -1.3 5 kg, [-5.76 to 3.06], p = 0.55). In adulthood, there also were no significant differences between groups in weight z-score (2 trials, 199 adults; MD -0.11, [-0.72 to 0.50], p = 0.73) and height z-score (2 trials, 199 adults; MD -0.07, [-0.36 to 0.22], p = 0.62). In subgroup analysis, supplementation was associated with increased length/height in toddler boys (2 trials, 173 boys; MD 1.66 cm, [0.75 to 2.58], p = 0.0003), but not girls (2 trials, 159 girls; MD 0.15 cm, [-0.71 to 1.01], p = 0.74). Limitations include considerable unexplained heterogeneity, low to very low quality of evidence, and possible bias due to low or unbalanced followup. CONCLUSIONS In this systematic review and meta-analysis, we found no evidence that early macronutrient supplementation for infants born small altered BMI in childhood. Although supplements appeared to increase weight and length in toddlers, effects were inconsistent and unlikely to be clinically significant. Limited data suggested that supplementation increased fat mass in childhood, but these effects did not persist in later life. PROSPERO registration: CRD42019126918.
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3.
Nutrients, Mitochondrial Function, and Perinatal Health.
Rodríguez-Cano, AM, Calzada-Mendoza, CC, Estrada-Gutierrez, G, Mendoza-Ortega, JA, Perichart-Perera, O
Nutrients. 2020;(7)
Abstract
Mitochondria are active independent organelles that not only meet the cellular energy requirement but also regulate central cellular activities. Mitochondria can play a critical role in physiological adaptations during pregnancy. Differences in mitochondrial function have been found between healthy and complicated pregnancies. Pregnancy signifies increased nutritional requirements to support fetal growth and the metabolism of maternal and fetal tissues. Nutrient availability regulates mitochondrial metabolism, where excessive macronutrient supply could lead to oxidative stress and contribute to mitochondrial dysfunction, while micronutrients are essential elements for optimal mitochondrial processes, as cofactors in energy metabolism and/or as antioxidants. Inadequate macronutrient and micronutrient consumption can result in adverse pregnancy outcomes, possibly through mitochondrial dysfunction, by impairing energy supply, one-carbon metabolism, biosynthetic pathways, and the availability of metabolic co-factors which modulate the epigenetic processes capable of establishing significant short- and long-term effects on infant health. Here, we review the importance of macronutrients and micronutrients on mitochondrial function and its influence on maternal and infant health.
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4.
Calculating Protein Content of Expressed Breast Milk to Optimize Protein Supplementation in Very Low Birth Weight Infants with Minimal Effort-A Secondary Analysis.
Minarski, M, Maas, C, Engel, C, Heinrich, C, Böckmann, K, Bernhard, W, Poets, CF, Franz, AR
Nutrients. 2020;(5)
Abstract
Breast milk does not meet the nutritional needs of preterm infants, necessitating fortification. Breast milk is particularly variable in protein content, hence standardized (fixed dosage) supplementation results in inadequate supply. This was a secondary analysis of 589 breast milk protein content measurements of 51 mothers determined by mid-infrared spectroscopy during a clinical trial of higher versus lower protein supplementation in very low birth weight infants. Mothers (and breast milk samples) were divided into a test (41 mothers) and a validation cohort (10 mothers). In the test cohort, the decrease in protein content by day of lactation was modeled resulting in the breast milk-equation (BME)). In the validation cohort, five supplementation strategies to optimize protein supply were compared: standardized supplementation (adding 1.0 g (S1) or 1.42 g protein/100 mL (S2)) was compared with 'adapted' supplementation, considering variation in protein content (protein content according to Gidrewicz and Fenton (A1), to BME (A2) and to BME with adjustments at days 12 and 26 (A3)). S1 and S2 achieved 5% and 24% of adequate protein supply, while the corresponding values for A1-A3 were 89%, 96% and 95%. Adapted protein supplementation based on calculated breast milk protein content is easy, non-invasive, inexpensive and improves protein supply compared to standardized supplementation.
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5.
Influence of a Functional Nutrients-Enriched Infant Formula on Language Development in Healthy Children at Four Years Old.
Nieto-Ruiz, A, Diéguez, E, Sepúlveda-Valbuena, N, Catena, E, Jiménez, J, Rodríguez-Palmero, M, Catena, A, Miranda, MT, García-Santos, JA, G Bermúdez, M, et al
Nutrients. 2020;(2)
Abstract
Nutrition during early life is essential for brain development and establishes the basis for cognitive and language skills development. It is well established that breastfeeding, compared to formula feeding, has been traditionally associated with increased neurodevelopmental scores up to early adulthood. We analyzed the long-term effects of a new infant formula enriched with bioactive compounds on healthy children's language development at four years old. In a randomized double-blind COGNIS study, 122 children attended the follow-up call at four years. From them, 89 children were fed a standard infant formula (SF, n = 46) or an experimental infant formula enriched with functional nutrients (EF, n = 43) during their first 18 months of life. As a reference group, 33 exclusively breastfed (BF) were included. Language development was assessed using the Oral Language Task of Navarra-Revised (PLON-R). ANCOVA, chi-square test, and logistic regression models were performed. EF children seemed to show higher scores in use of language and oral spontaneous expression than SF children, and both SF and EF groups did not differ from the BF group. Moreover, it seems that SF children were more frequently categorized into "need to improve and delayed" in the use of language than EF children, and might more frequently present "need to improve and delayed" in the PLON-R total score than BF children. Finally, the results suggest that SF children presented a higher risk of suffering language development than BF children. Secondary analysis also showed a slight trend between low socioeconomic status and poorer language skills. The functional compound-enriched infant formula seems to be associated with beneficial long-term effects in the development of child's language at four years old in a similar way to breastfed infants.
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6.
Non-IgE-mediated food allergy during infancy.
Devonshire, AL, Durrani, S, Assa'ad, A
Current opinion in allergy and clinical immunology. 2020;(3):292-298
Abstract
PURPOSE OF REVIEW Is to highlight the recent advances in the diagnosis and management of non-IgE-mediated food allergy which is a common consideration in primary care and in allergy and gastroenterology subspecialty practices evaluating infants. RECENT FINDINGS The review focuses on food protein-induced enterocolitis syndrome (FPIES) and includes other non-IgE-mediated food allergy in nursing infants, food protein-induced allergic proctocolitis, and food protein-induced enteropathy. For FPIES, we review the 2017 International Consensus Guidelines that provided the first comprehensive framework for its diagnosis and management and that were supplemented by a 2019 position paper by the European Academy of Allergy and Clinical Immunology. We review recent reports that support FPIES as a diagnosis of primarily infants, highlight the problem of delayed diagnosis, reveal the need for improved biomarkers, emphasize new and common food protein triggers, and identify new approaches for evaluation of tolerance. SUMMARY As formal diagnostic criteria for non-IgE-mediated food allergies are defined and prevalence data is increasingly reported, there will likely be improved recognition and evaluation of these conditions. Currently, large-scale prospective studies evaluating their incidence and prevalence, associated risk factors, and natural history are needed. Although avoidance of the suspected trigger food protein remains the cornerstone of management, additional studies of underlying pathophysiology and biomarkers of disease will likely reveal new avenues for therapeutics.
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7.
The Impact of Dietary Fucosylated Oligosaccharides and Glycoproteins of Human Milk on Infant Well-Being.
Orczyk-Pawiłowicz, M, Lis-Kuberka, J
Nutrients. 2020;(4)
Abstract
Apart from optimal nutritional value, human milk is the feeding strategy to support the immature immunological system of developing newborns and infants. The most beneficial dietary carbohydrate components of breast milk are human milk oligosaccharides (HMOs) and glycoproteins (HMGs), involved in both specific and nonspecific immunity. Fucosylated oligosaccharides represent the largest fraction of human milk oligosaccharides, with the simplest and the most abundant being 2'-fucosyllactose (2'FL). Fucosylated oligosaccharides, as well as glycans of glycoproteins, as beneficial dietary sugars, elicit anti-adhesive properties against fucose-dependent pathogens, and on the other hand are crucial for growth and metabolism of beneficial bacteria, and in this aspect participate in shaping a healthy microbiome. Well-documented secretor status related differences in the fucosylation profile of HMOs and HMGs may play a key but underestimated role in assessment of susceptibility to fucose-dependent pathogen infections, with a potential impact on applied clinical procedures. Nevertheless, due to genetic factors, about 20% of mothers do not provide their infants with beneficial dietary carbohydrates such as 2'-FL and other α1,2-fucosylated oligosaccharides and glycans of glycoproteins, despite breastfeeding them. The lack of such structures may have important implications for a wide range of aspects of infant well-being and healthcare. In light of the above, some artificial mixtures used in infant nutrition are supplemented with 2'-FL to more closely approximate the unique composition of maternal milk, including dietary-derived fucosylated oligosaccharides and glycoproteins.
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8.
The Impact of Human Milk on Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis.
Altobelli, E, Angeletti, PM, Verrotti, A, Petrocelli, R
Nutrients. 2020;(5)
Abstract
BACKGROUND Premature infants receiving breastfeed have a lower incidence of NEC than those fed preterm formula. This study aimed: (1) to update a systematic review and meta-analyses to evaluate the relationship between feeding and necrotizing enterocolitis (NEC) in low weight premature infants; (2) to conduct meta-regression analyses by subgroups; (3) to describe geographical distribution of milk banks in the world. METHODS Papers included in the meta-analysis were updated as of June 2019. Relative risks were used as a measure of effect size. Random effect models were used to account for different sources of variation among studies. For milk banks, the data reviewed by the literature were integrated with the information collected from countries' institutional sites and milk bank networks. RESULTS Thirty-two papers were included in meta-analysis: six randomized controlled trials (RCTs) and 26 observational studies (OS). The census has found 572 milk banks around in the world. Brazil has the most active milk banks. RCTs meta-analysis indicates a risk reduction of NEC using human milk respect to formula: Relative risk (RR) = 0.62 (0.42-0.93). Seven OS compared quantities lower than human milk or higher than the 50th quantile showing a risk reduction of NEC:RR = 0.51 (0.31-0.85); 3 OS that evaluated human milk versus mixed feeding showing that human milk has a protective role on the development of NEC:RR = 0.74 (0.63-0.91). Results of subgroups analysis show that the risk reduction is statistically significant only for studies in which premature infants are given both their own and donated breastmilk. CONCLUSIONS The possibility of preserving human milk and promoting donations guarantees an improvement in the health of newborns.
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9.
Bifidobacterium longum Subspecies infantis (B. infantis) in Pediatric Nutrition: Current State of Knowledge.
Chichlowski, M, Shah, N, Wampler, JL, Wu, SS, Vanderhoof, JA
Nutrients. 2020;(6)
Abstract
Abstract: Since originally isolated in 1899, the genus Bifidobacterium has been demonstrated to predominate in the gut microbiota of breastfed infants and to benefit the host by accelerating maturation of the immune response, balancing the immune system to suppress inflammation, improving intestinal barrier function, and increasing acetate production. In particular, Bifidobacterium longum subspecies infantis (B. infantis) is well adapted to the infant gut and has co-evolved with the mother-infant dyad and gut microbiome, in part due to its ability to consume complex carbohydrates found in human milk. B. infantis and its human host have a symbiotic relationship that protects the preterm or term neonate and nourishes a healthy gut microbiota prior to weaning. To provide benefits associated with B. infantis to all infants, a number of commercialized strains have been developed over the past decades. As new ingredients become available, safety and suitability must be assessed in preclinical and clinical studies. Consideration of the full clinical evidence for B. infantis use in pediatric nutrition is critical to better understand its potential impacts on infant health and development. Herein we summarize the recent clinical studies utilizing select strains of commercialized B. infantis.
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10.
Composition of Coloured Gastric Residuals in Extremely Preterm Infants-A Nested Prospective Observational Study.
Athalye-Jape, G, Nettleton, M, Lai, CT, Nathan, E, Geddes, D, Simmer, K, Patole, S
Nutrients. 2020;(9)
Abstract
Green gastric residuals (GR) are often considered as a sign of feed intolerance and discarded in preterm infants. Probiotics are known to enhance feed tolerance in preterm infants. To assess the composition (primary outcome) and volume of discarded green GRs, and feeding outcomes in extremely preterm (EP) infants in a probiotic trial, composition of pale and dark green GRs in the first two weeks of life from EP infants (<28 weeks) in a randomized controlled trial (RCT: SiMPro) of single vs. three-strain probiotics was assessed. Feeding outcomes included time to full feeds (TFF: 150 mL/kg/day) and duration of parenteral nutrition (PN). EP infants given placebo in our previous probiotic RCT served as the reference group. Analysis involved linear regression modelling with clustered standard errors for repeated measurements. GRs of 74/103 from 39 SiMPro infants (18: single-strain, 21: three-strain) were analyzed. Bile acid content was higher but statistically insignificant (825.79 vs. 338.1 µmol/L; p = 0.12) in dark vs. pale green GRs. Mean (95% confidence interval) fat, nitrogen, and carbohydrate loss in GRs over the study period was 0.02 g (0.01-0.03), 0.011 g (0.009-0.013), and 0.05 g (0.04-0.06), respectively. Overall, SiMPro infants had shorter median TFF (10 vs. 14 days, p = 0.02) and duration of PN (10 vs. 16 days, p = 0.022) compared with control group infants. Z scores for growth parameters at discharge were comparable. Discarding dark green GRs meant higher loss of bile acids during early enteral nutrition in EP infants. Probiotic supplementation was associated with reduced TFF and duration of PN.