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1.
Effects on Growth of Smell and Taste of Milk During Tube Feeding of Preterm Infants: A Randomized Clinical Trial.
Beker, F, Liley, HG, Hughes, IP, Jacobs, SE, Macey, J, Twitchell, E, Davis, PG
JAMA pediatrics. 2021;(11):1115-1123
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Abstract
IMPORTANCE Smell and taste of food increase food anticipation, activate gut motility, and stimulate digestion and metabolism. Despite poor growth of many preterm infants in neonatal intensive care units, the smell and taste of milk with tube feeding are not generally considered a regular component of care. OBJECTIVE To determine the effect of smell and taste of milk with tube feeding on weight z scores at discharge from the hospital. DESIGN, SETTING, AND PARTICIPANTS A randomized, controlled, nonblinded, superiority trial was conducted at 2 perinatal centers between May 9, 2017, and February 1, 2020. Eligible infants (n = 659) were born at less than 29 weeks' postmenstrual age (PMA) and/or with a birth weight of less than 1250 g. INTERVENTIONS Infants were randomly assigned to receive either the smell and taste of milk with each tube feeding or routine care without the provision of smell and taste of milk. MAIN OUTCOMES AND MEASURES The primary outcome was weight z score at discharge from any hospital. Secondary outcomes included anthropometric measures at predefined time points, time to full enteral feeds, and other health outcomes associated with prematurity. RESULTS Of the 658 infants, a total of 396 infants were randomized; some parents had not been approached for consent (n = 144) or declined participation (n = 117), and 1 infant with consent was not randomized. Of the 396 infants, 196 were assigned to the treatment group (51% male; mean [SD] PMA at birth, 27.5 [2.2] weeks) and 200 were assigned to the control group (52% male; mean [SD] PMA at birth, 27.6 (2.3) weeks). Mean weight z scores at discharge were -0.87 (95% CI, -1.02 to -0.72) for the treatment group and -0.97 (95% CI, -1.11 to -0.83) for the control group (P = .40). The mean difference in z scores between the treatment and control groups at 36 weeks' PMA was 0.21 (95% CI, 0.01 to 0.4; P = .04) for head circumference and 0.26 (95% CI, 0.05 to 0.51; P = .04) for length. There were no clinically notable differences between the study groups for any other anthropometric, feeding, or health outcomes. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, regular smell and taste of milk included with tube feeding did not improve weight at discharge in preterm infants. Secondary outcomes suggest exposure to smell and taste may improve head circumference and length at 36 weeks' PMA, but not at discharge. Regular exposure to the smell and taste of milk is a simple and inexpensive intervention with potential benefits and no apparent adverse effects. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12617000583347.
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High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants.
Abiramalatha, T, Thomas, N, Thanigainathan, S
The Cochrane database of systematic reviews. 2021;(3):CD012413
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Abstract
BACKGROUND Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease. This is an update of a review published in 2017. OBJECTIVES To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge. MAIN RESULTS We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review. High versus standard volume feeds with fortified human milk or preterm formula Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta-analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate-certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI -0.02 to 0.13; participants = 271; low-certainty evidence), head growth (MD 0.02 cm/week, 95% CI -0.04 to 0.09; participants = 271; low-certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low-certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very-low certainty evidence). High versus standard volume feeds with unfortified human milk or term formula One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate-certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low-certainty evidence). AUTHORS' CONCLUSIONS High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice.
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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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Clinical Results of the Implementation of a Breast Milk Bank in Premature Infants (under 37 Weeks) at the Hospital Universitario del Valle 2018-2020.
Torres-Muñoz, J, Jimenez-Fernandez, CA, Murillo-Alvarado, J, Torres-Figueroa, S, Castro, JP
Nutrients. 2021;(7)
Abstract
Breast milk is widely recognized as the best source of nutrition for both full term and premature babies. We aimed to identify clinical results of the implementation of a breast milk bank for premature infants under 37 weeks in a level III hospital. 722 neonates under 37 weeks, hospitalized in the Neonatal intensive care unit (ICU), who received human breast milk from the institution's milk bank 57% (n = 412) vs. mixed or artificial 32% (n = 229), at day 7 of life. An exploratory data analysis was carried out. Measures of central tendency and dispersion were used, strength of association of odds ratio (OR) and its confidence intervals (95% confidence interval (CI)). 88.5% had already received human milk before day 7 of life. Those who received human milk, due to their clinical condition, had 4 times a greater chance of being intubated (OR 4.05; 95% CI 1.80-9.11). Starting before day 7 of life decreases the opportunity to develop necrotizing enterocolitis by 82% (adjusted odds ratio (ORa) 0.18; 95% CI 0.03-0.97), intraventricular hemorrhage by 85% (ORa 0.15; 95% CI 0.06-0.45) and sepsis by 77% (ORa 0.23; 95% CI 0.15-0.33). Receiving human milk reduces the probability of complications related to prematurity, evidencing the importance that breast milk banks play in clinical practice.
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Correlation between hyperglycemia and glycated albumin with retinopathy of prematurity.
Almeida, AC, Silva, GA, Santini, G, Brízido, M, Correia, M, Coelho, C, Borrego, LM
Scientific reports. 2021;(1):22321
Abstract
To determine the association between hyperglycemia, glycated albumin (GlyA) and retinopathy of prematurity (ROP). Prospective study of all infants under ROP screening from March 2017 to July 2019. All demographic, clinical and laboratory data were collected. Glucose was measured at birth and every 8 h for the first week and serum GlyA was evaluated at birth, 1st, 2nd and 4th weeks after birth. Reference range for GlyA was obtained. Univariate logistic regression was used to examine risk factors for ROP followed by multivariate regression. A total of 152 infants were included in the study. Median gestational age was 30 weeks and median birth weight 1240 g. Thirty-three infants (21.7%) had ROP. Hyperglycemia was present in 24 (72.7%) infants diagnosed with any ROP versus 6 (0.05%) in those without ROP. Median GlyA at birth, 1st, 2nd and 4th and respective reference ranges were 8.50% (6.00-12.65), 8.20% (5.32-11.67), 8.00% (5.32-10.00) and 7.90% (5.30-9.00) respectively. After multivariate logistic regression, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors (Exp (B) 28.062, 95% CI for Exp(B) 7.881-99.924 p < 0.001). In our cohort, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors.
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Early Enteral Feeding Improves Tolerance of Parenteral Nutrition in Preterm Newborns.
Boscarino, G, Conti, MG, Di Chiara, M, Bianchi, M, Onestà, E, Faccioli, F, Deli, G, Repole, P, Oliva, S, Cresi, F, et al
Nutrients. 2021;(11)
Abstract
(1) Background: The tolerance of preterm newborns for the high nutritional intakes given by parenteral nutrition (PN) is still debated because of the risk of metabolic complications. Despite enteral nutrition (EN) being the preferred route of nutrition, an exclusive enteral feeding is not always possible, as in preterm newborns, the gut is immature and less tolerant of EN. We aimed to study the impact of a minimal enteral feeding (MEF) on the possible early metabolic complications of PN in a cohort of preterms with gestational age at birth GA ≤ 29 + 6/7 weeks of postmenstrual age. (2) Methods: We divided the study sample in two cohorts: 1) Late-Feeding (cohort 1), newborns who received MEF starting from the 8th day of age, and (2) Early-Feeding (cohort 2), newborns who received MEF, consisting of the administration of at least 4-5 mL/kg/day by the enteral route, in the first 7 days of age. The primary outcome of the study was the rate of at least one metabolic complication, including hyperglycemia, hypertriglyceridemia, or metabolic acidosis. (3) Results: We enrolled 80 newborns (Late-Feeding cohort 51 vs. Early-Feeding cohort 29). The rate of all metabolic complications was statistically higher in the Late-Feeding cohort compared to the Early-Feeding cohort. Binary logistic regression analysis showed that late administration of MEF negatively influenced the rate of all metabolic complications. (4) Conclusions: Early minimal administration of EN is associated with less frequent PN-related metabolic side effects and a higher rate of survival in critically ill newborns.
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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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Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review.
Fenton, TR, Groh-Wargo, S, Gura, K, Martin, CR, Taylor, SN, Griffin, IJ, Rozga, M, Moloney, L
Journal of the Academy of Nutrition and Dietetics. 2021;(11):2287-2300.e12
Abstract
Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.
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Feeding the preterm infant: an overview of the evidence.
Poulimeneas, D, Bathrellou, E, Antonogeorgos, G, Mamalaki, E, Kouvari, M, Kuligowski, J, Gormaz, M, Panagiotakos, DB, Yannakoulia, M, ,
International journal of food sciences and nutrition. 2021;(1):4-13
Abstract
Feeding from own mother's milk is not always an option for preterm infants, and choosing between alternative means of feeding should be made in light of their effect on infants' health. In this work, we aimed to present evidence regarding feeding pre-term infants with human milk, either own mother's or donor milk (DM), and the potential effects on growth and other health related outcomes. Exclusive breastfeeding (BF) remains the optimal option, whereas feeding with DM as a sole diet or supplemental to maternal milk confers immunological advantages and fewer rates of necrotising enterocolitis against preterm formula feeding, yet the latter results in greater growth velocity. Literature gaps in the use of DM, practical suggestions for choosing suitable feeding means (i.e. continuous support of BF, adequate education regarding feeding preterm infants, including DM), and future perspectives on the potential effects of dietary manipulations of the maternal diet, are also discussed.
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Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial.
Rochow, N, Fusch, G, Ali, A, Bhatia, A, So, HY, Iskander, R, Chessell, L, El Helou, S, Fusch, C
Clinical nutrition (Edinburgh, Scotland). 2021;(1):54-63
Abstract
BACKGROUND & AIMS In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. METHODS This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed - protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. RESULTS Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n = 52, control n = 51). The intervention group infants had higher macronutrient intakes, weight gain (21.2 ± 2.5 vs 19.3 ± 2.4 g/kg/d, mean difference: 1.9 g/kg/d, 95% CI: 0.9 - 2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580 ± 280 g vs 2210 ± 300 g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. CONCLUSIONS This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.