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Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants.
Ottolini, KM, Schulz, EV, Limperopoulos, C, Andescavage, N
Nutrients. 2021;(12)
Abstract
Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth-particularly brain development-that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification-including targeted and adjusted fortification-show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.
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Early Enteral Feeding in Preterm Infants: A Narrative Review of the Nutritional, Metabolic, and Developmental Benefits.
Thoene, M, Anderson-Berry, A
Nutrients. 2021;(7)
Abstract
Enteral feeding is the preferred method of nutrient provision for preterm infants. Though parenteral nutrition remains an alternative to provide critical nutrition after preterm delivery, the literature suggests that enteral feeding still confers significant nutritional and non-nutritional benefits. Therefore, the purpose of this narrative review is to summarize health and clinical benefits of early enteral feeding within the first month of life in preterm infants. Likewise, this review also proposes methods to improve enteral delivery in clinical care, including a proposal for decision-making of initiation and advancement of enteral feeding. An extensive literature review assessed enteral studies in preterm infants with subsequent outcomes. The findings support the early initiation and advancement of enteral feeding impact preterm infant health by enhancing micronutrient delivery, promoting intestinal development and maturation, stimulating microbiome development, reducing inflammation, and enhancing brain growth and neurodevelopment. Clinicians must consider these short- and long-term implications when caring for preterm infants.
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Short versus long feeding interval for bolus feedings in very preterm infants.
Ibrahim, NR, Van Rostenberghe, H, Ho, JJ, Nasir, A
The Cochrane database of systematic reviews. 2021;(8):CD012322
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Abstract
BACKGROUND There is presently no certainty about the ideal feeding intervals for preterm infants. Shorter feeding intervals of, for example, two hours, have the theoretical advantage of allowing smaller volumes of milk. This may have the potential to reduce the incidence and severity of gastro-oesophageal reflux. Longer feeding intervals have the theoretical advantage of allowing more gastric emptying between two feeds. This potentially provides periods of rest (and thus less hyperaemia) for an immature digestive tract. OBJECTIVES To determine the safety of shorter feeding intervals (two hours or shorter) versus longer feeding intervals (three hours or more) and to compare the effects in terms of days taken to regain birth weight and to achieve full feeding. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in CENTRAL (2020, Issue 6) and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions, and CINAHL on 25 June 2020. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA We included RCTs and quasi-RCTs comparing short (e.g. one or two hours) versus long (e.g. three or four hours) feeding intervals in preterm infants of any birth weight, all or most of whom were less than 32 weeks' gestation. Infants could be of any postnatal age at trial entry, but eligible infants should not have received feeds before study entry, with the exception of minimal enteral feeding. We included studies of nasogastric or orogastric bolus feeding, breast milk or formula, in which the feeding interval is the intervention. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were days taken to achieve full enteral feeding and days to regain birth weight. Our other outcomes were duration of hospital stay, episodes of necrotising enterocolitis (NEC) and growth during hospital stay (weight, length and head circumference). MAIN RESULTS We included four RCTs, involving 417 infants in the review. One study involving 350 infants is awaiting classification. All studies compared two-hourly versus three-hourly feeding interval. The risk of bias of the included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies were included in meta-analysis for the number of days taken to achieve full enteral feeding (351 participants). The mean days to achieve full feeds was between eight and 11 days. There was little or no difference in days taken to achieve full enteral feeding between two-hourly and three-hourly feeding, but this finding was of low certainty (mean difference (MD) ‒0.62, 95% confidence interval (CI) ‒1.60 to 0.36). There was low-certainty evidence that the days taken to regain birth weight may be slightly longer in infants receiving two-hourly feeding than in those receiving three-hourly feeding (MD 1.15, 95% CI 0.11 to 2.20; 3 studies, 350 participants). We are uncertain whether shorter feeding intervals have any effect on any of our secondary outcomes including the duration of hospital stay (MD ‒3.36, 95% CI ‒9.18 to 2.46; 2 studies, 207 participants; very low-certainty evidence) and the risk of NEC (typical risk ratio 1.07, 95% CI 0.54 to 2.11; 4 studies, 417 participants; low-certainty evidence). No study reported growth during hospital stay. AUTHORS' CONCLUSIONS The low-certainty evidence we found in this review suggests that there may be no clinically important differences between two- and three-hourly feeding intervals. There is insufficient information about potential feeding complications and in particular NEC. No studies have looked at the effect of other feeding intervals and there is no long-term data on neurodevelopment or growth.
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Bacillus cereus Induces Severe Infections in Preterm Neonates: Implication at the Hospital and Human Milk Bank Level.
Cormontagne, D, Rigourd, V, Vidic, J, Rizzotto, F, Bille, E, Ramarao, N
Toxins. 2021;(2)
Abstract
Human breast milk (HBM) is a source of essential nutrients for infants and is particularly recommended for preterm neonates when their own mother's milk is not available. It provides protection against infections and decreases necrotizing enterocolitis and cardiovascular diseases. Nevertheless, HBM spoilage can occur due to contamination by pathogens, and the risk of a shortage of HBM is very often present. B. cereus is the most frequent ubiquitous bacteria responsible for HBM being discarded. It can contaminate HBM at all stages, from its collect point to the storage and delivery. B. cereus can induce severe infection in newborns with very low birth weight, with sometimes fatal outcomes. Although the source of contamination is rarely identified, in some cases, HBM was suspected as a potential source. Even if the risk is low, as infection due to B. cereus in preterm infants should not be overlooked, human milk banks follow strict procedures to avoid contamination, to accurately identify remaining bacteria following pasteurization and to discard non-compliant milk samples. In this review, we present a literature overview of B. cereus infections reported in neonates and the suspected sources of contamination. We highlight the procedures followed by the human milk banks from the collection of the milk to its microbiological characterization in Europe. We also present improved detection and decontamination methods that might help to decrease the risk and to preserve the public's confidence in this vital biological product for infants whose mothers cannot breastfeed.
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Iron and Neurodevelopment in Preterm Infants: A Narrative Review.
German, KR, Juul, SE
Nutrients. 2021;(11)
Abstract
Iron is critical for brain development, playing key roles in synaptogenesis, myelination, energy metabolism and neurotransmitter production. NICU infants are at particular risk for iron deficiency due to high iron needs, preterm birth, disruptions in maternal or placental health and phlebotomy. If deficiency occurs during critical periods of brain development, this may lead to permanent alterations in brain structure and function which is not reversible despite later supplementation. Children with perinatal iron deficiency have been shown to have delayed nerve conduction speeds, disrupted sleep patterns, impaired recognition memory, motor deficits and lower global developmental scores which may be present as early as in the neonatal period and persist into adulthood. Based on this, ensuring brain iron sufficiency during the neonatal period is critical to optimizing neurodevelopmental outcomes and iron supplementation should be targeted to iron measures that correlate with improved outcomes.
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Fat and Fat-Free Mass of Preterm and Term Infants from Birth to Six Months: A Review of Current Evidence.
Hamatschek, C, Yousuf, EI, Möllers, LS, So, HY, Morrison, KM, Fusch, C, Rochow, N
Nutrients. 2020;(2)
Abstract
To optimize infant nutrition, the nature of weight gain must be analyzed. This study aims to review publications and develop growth charts for fat and fat-free mass for preterm and term infants. Body composition data measured by air displacement plethysmography (ADP) and dual energy X-ray absorptiometry (DXA) in preterm and term infants until six months corrected age were abstracted from publications (31 December 1990 to 30 April 2019). Age-specific percentiles were calculated. ADP measurements were used in 110 studies (2855 preterm and 22,410 term infants), and DXA was used in 28 studies (1147 preterm and 3542 term infants). At term age, preterm infants had higher percent-fat than term-born infants (16% vs. 11%, p < 0.001). At 52 weeks postmenstrual age (PMA), both reached similar percent-fat (24% vs. 25%). In contrast, at term age, preterm infants had less fat-free mass (2500 g vs. 2900 g) by 400 g. This difference decreased to 250 g by 52 weeks, and to 100 g at 60 weeks PMA (5000 g vs. 5100 g). DXA fat-free mass data were comparable with ADP. However, median percent-fat was up to 5% higher with DXA measurements compared with ADP with PMA > 50 weeks. There are methodological differences between ADP and DXA measures for infants with higher fat mass. The cause of higher fat mass in preterm infants at term age needs further investigation.
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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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Language nutrition for language health in children with disorders: a scoping review.
Bang, JY, Adiao, AS, Marchman, VA, Feldman, HM
Pediatric research. 2020;(2):300-308
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Abstract
The quantity and quality of child-directed speech-language nutrition-provided to typically-developing children is associated with language outcomes-language health. Limited information is available about child-directed speech to children at biological risk of language impairments. We conducted a scoping review on caregiver child-directed speech for children with three clinical conditions associated with language impairments-preterm birth, intellectual disability, and autism-addressing three questions: (1) How does child-directed speech to these children differ from speech to typically-developing children? (2) What are the associations between child-directed speech and child language outcomes? (3) How convincing are intervention studies that aim to improve child-directed speech and thereby facilitate children's language development? We identified 635 potential studies and reviewed 57 meeting study criteria. Child-directed speech to children with all conditions was comparable to speech to language-matched children; caregivers were more directive toward children with disorders. Most associations between child-directed speech and outcomes were positive. However, several interventions had minimal effects on child language. Trials with large samples, intensive interventions, and multiple data sources are needed to evaluate child-directed speech as a means to prevent language impairment. Clinicians should counsel caregivers to use high quality child-directed speech and responsive communication styles with children with these conditions.
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Invited Review: Factors associated with atypical brain development in preterm infants: insights from magnetic resonance imaging.
Boardman, JP, Counsell, SJ
Neuropathology and applied neurobiology. 2020;(5):413-421
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Abstract
Preterm birth (PTB) is a leading cause of neurodevelopmental and neurocognitive impairment in childhood and is closely associated with psychiatric disease. The biological and environmental factors that confer risk and resilience for healthy brain development and long-term outcome after PTB are uncertain, which presents challenges for risk stratification and for the discovery and evaluation of neuroprotective strategies. Neonatal magnetic resonance imaging reveals a signature of PTB that includes dysconnectivity of neural networks and atypical development of cortical and deep grey matter structures. Here we provide a brief review of perinatal factors that are associated with the MRI signature of PTB. We consider maternal and foetal factors including chorioamnionitis, foetal growth restriction, socioeconomic deprivation and prenatal alcohol, drug and stress exposures; and neonatal factors including co-morbidities of PTB, nutrition, pain and medication during neonatal intensive care and variation conferred by the genome/epigenome. Association studies offer the first insights into pathways to adversity and resilience after PTB. Future challenges are to analyse quantitative brain MRI data with collateral biological and environmental data in study designs that support causal inference, and ultimately to use the output of such analyses to stratify infants for clinical trials of therapies designed to improve outcome.
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Vitamin D in Preterm and Full-Term Infants.
Abrams, SA
Annals of nutrition & metabolism. 2020;:6-14
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Abstract
Vitamin D is necessary for the active (transcellular) absorption of calcium and for skeletal health. Inadequate vitamin D in infants leads to increased risks of poor bone mineralization and ultimately rickets. Rickets is uncommon in full-term infants with a much higher risk in very premature infants. However, the primary cause of rickets in premature infants is a deficiency of calcium and phosphorus, not vitamin D. Available research, as well as most guidelines, recommend an intake of 400 IU daily of vitamin D as adequate for bone health in preterm and full-term infants. Higher doses have not been consistently shown to have specific clinical benefits for healthy infants. There are no strong data to support either routine testing of serum 25-hydroxyvitamin D or targeting high serum 25-hydroxyvitamin D levels (e.g., 30 ng/mL) in healthy preterm or full-term infants. Vitamin D is commonly provided to infants via drops for breastfed babies or via infant formula, although alternative dosing approaches exist for breastfed infants, which some families may prefer. These include the use of drops placed on the mother's breast, dissolvable doses, and high maternal doses (approximately 6,400 IU daily). Infant formula contains vitamin D, and most infants will reach an intake from formula of about 400 IU daily within the first 2 months of life if they are consuming routine cow milk-based formula. Although vitamin D toxicity is very uncommon, caution should be used to avoid extremely concentrated high doses found in some commercially available drops. Infants with liver or kidney disease may need special attention to vitamin D intake and status. Further research is needed to define the role of vitamin D in non-bone health outcomes of infants and to identify methods to enhance compliance with current recommendations for vitamin D intake in infants.