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Nutrient-enriched formula versus standard formula for preterm infants.
Walsh, V, Brown, JVE, Askie, LM, Embleton, ND, McGuire, W
The Cochrane database of systematic reviews. 2019;(7):CD004204
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Abstract
BACKGROUND Preterm infants may accumulate nutrient deficits leading to extrauterine growth restriction. Feeding preterm infants with nutrient-enriched rather than standard formula might increase nutrient accretion and growth rates and might improve neurodevelopmental outcomes. OBJECTIVES To compare the effects of feeding with nutrient-enriched formula versus standard formula on growth and development of preterm infants. SEARCH METHODS We used the Cochrane Neonatal standard search strategy. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (until November 2018), as well as conference proceedings, previous reviews, and clinical trials databases. SELECTION CRITERIA Randomised and quasi-randomised controlled trials that compared feeding preterm infants with nutrient-enriched formula (protein and energy plus minerals, vitamins, or other nutrients) versus standard formula. DATA COLLECTION AND ANALYSIS We extracted data using the Cochrane Neonatal standard methods. Two review authors separately evaluated trial quality and extracted and synthesised data using risk ratios (RRs), risk differences, and mean differences (MDs). We assessed certainty of evidence at the outcome level using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS We identified seven trials in which a total of 590 preterm infants participated. Most participants were clinically stable preterm infants of birth weight less than 1850 g. Few participants were extremely preterm, extremely low birth weight, or growth restricted at birth. Trials were conducted more than 30 years ago, were formula industry funded, and were small with methodological weaknesses (including lack of masking) that might bias effect estimates. Meta-analyses of in-hospital growth parameters were limited by statistical heterogeneity. There is no evidence of an effect on time to regain birth weight (MD -1.48 days, 95% confidence interval (CI) -4.73 to 1.77) and low-certainty evidence suggests that feeding with nutrient-enriched formula increases in-hospital rates of weight gain (MD 2.43 g/kg/d, 95% CI 1.60 to 3.26) and head circumference growth (MD 1.04 mm/week, 95% CI 0.18 to 1.89). Meta-analysis did not show an effect on the average rate of length gain (MD 0.22 mm/week, 95% CI -0.70 to 1.13). Fewer data are available for growth and developmental outcomes assessed beyond infancy, and these do not show consistent effects of nutrient-enriched formula feeding. Data from two trials did not show an effect on Bayley Mental Development Index scores at 18 months post term (MD 2.87, 95% CI -1.38 to 7.12; moderate-certainty evidence). Infants who received nutrient-enriched formula had higher Bayley Psychomotor Development Index scores at 18 months post term (MD 6.56. 95% CI 2.87 to 10.26; low-certainty evidence), but no evidence suggested an effect on cerebral palsy (typical RR 0.79, 95% CI 0.30 to 2.07; 2 studies, 377 infants). Available data did not indicate any other benefits or harms and provided low-certainty evidence about the effect of nutrient-enriched formula feeding on the risk of necrotising enterocolitis in preterm infants (typical RR 0.72, 95% CI 0.41 to 1.25; 3 studies, 489 infants). AUTHORS' CONCLUSIONS Available trial data show that feeding preterm infants nutrient-enriched (compared with standard) formulas has only modest effects on growth rates during their initial hospital admission. No evidence suggests effects on long-term growth or development. The GRADE assessment indicates that the certainty of this evidence is low, and that these findings should be interpreted and applied with caution. Further randomised trials would be needed to resolve this uncertainty.
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2.
Formula versus donor breast milk for feeding preterm or low birth weight infants.
Quigley, M, Embleton, ND, McGuire, W
The Cochrane database of systematic reviews. 2019;(7):CD002971
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Abstract
BACKGROUND When sufficient maternal breast milk is not available, alternative forms of enteral nutrition for preterm or low birth weight (LBW) infants are donor breast milk or artificial formula. Donor breast milk may retain some of the non-nutritive benefits of maternal breast milk for preterm or LBW infants. However, feeding with artificial formula may ensure more consistent delivery of greater amounts of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or LBW infants. OBJECTIVES To determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight (LBW) infants. SEARCH METHODS We used the Cochrane Neonatal search strategy, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5), Ovid MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (3 May 2019), as well as conference proceedings, previous reviews, and clinical trials. SELECTION CRITERIA Randomised or quasi-randomised controlled trials (RCTs) comparing feeding with formula versus donor breast milk in preterm or LBW infants. DATA COLLECTION AND ANALYSIS Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios (RRs) and risk differences (RDs) for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in subgroup analyses. We assessed the certainty of evidence for the main comparison at the outcome level using GRADE methods. MAIN RESULTS Twelve trials with a total of 1879 infants fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and eight compared nutrient-enriched preterm formula versus donor breast milk. Only the five most recent trials used nutrient-fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials. Most of the included trials were funded by companies that made the study formula.Formula-fed infants had higher in-hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). These meta-analyses contained high levels of heterogeneity. We did not find evidence of an effect on long-term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.05; number needed to treat for an additional harmful outcome (NNTH) 33, 95% CI 20 to 100; 9 studies, 1675 infants).The GRADE certainty of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all-cause mortality, and necrotising enterocolitis (downgraded for imprecision). AUTHORS' CONCLUSIONS In preterm and LBW infants, moderate-certainty evidence indicates that feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all-cause mortality, or on long-term growth or neurodevelopment.
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Differences in energy expenditure in human donor milk versus formula milk in preterm newborns: A crossover study.
Soares, FVM, Abranches, AD, Méio, MDBB, Gomes, SC, Villela, LD, Moreira, MEL
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:1-4
Abstract
OBJECTIVE The aim of this study was to compare the ratio between energy expenditure and caloric density in human donor milk versus formula milk in preterm newborn infants. METHODS This was a crossover, randomized clinical trial with 29 preterm newborn infants receiving full diet. The infants were randomly assigned to receive either human milk or formula milk alternating, after a 24-h period. Energy expenditure was evaluated by indirect calorimetry. Total calorie and macronutrient values in the human milk were calculated individually with infrared technique; energy expenditure/caloric density ratio was calculated. RESULTS Human donor milk energy expenditure/caloric density ratio was significantly greater than in formula milk at all time points. The total mean was 1.04 ± 0.27 for the human milk and 0.81 ± 0.11 for the formula. However, when we analyzed a subgroup of newborns that received human donor milk with >60 kcal/100 mL, there was no statistical difference (P = 0.36). The mean calorie values were 58.9 kcal/100 mL (human donor milk) and 81.4 kcal/100 mL (formula milk). CONCLUSION Formula milk produced a better metabolic response than human donor milk. Human donor milk with higher caloric content showed no difference from formula, so the use of human donor milk with more caloric density should be reinforced.
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[The first 1000 days: an opportunity to reduce the burden of noncommunicable diseases].
Moreno Villares, JM, Collado, MC, Larqué, E, Leis Trabazo, R, Saenz De Pipaón, M, Moreno Aznar, LA
Nutricion hospitalaria. 2019;(1):218-232
Abstract
Growth and development are determined by genetic and environmental factors since the very early embryonic life. Long-term health risks, as obesity and other non-communicable diseases (NCD), could be programmed since these early stages. Early life, characterized by plasticity, is the ideal time to intervene and to prevent the risk of suffering a NCD (window of opportunity). Optimal nutrition during the first 1,000 days, since conception to the end of the second year of life, has a determinant role for long-term health. Pregnancy, infancy and toddler periods have specific nutritional requirements. Intestinal microbiota enhances maturation and functioning of the immune system. The interactions between host and intestinal microbiota are potential factors influencing early programming of the intestinal function. Alterations in intestinal colonization are associated to a higher risk of allergic diseases in childhood. Scientific evidence supports the fact that the first 1,000 days are crucial to achieve a better long-term health and represents a strategic period to intervene under the perspective of prevention and public health.
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Optimized protein intakes in term infants support physiological growth and promote long-term health.
Koletzko, B, Demmelmair, H, Grote, V, Totzauer, M
Seminars in perinatology. 2019;(7):151153
Abstract
Breastfeeding is associated with a reduced later obesity risk, relative to feeding convention infant formula. Breastfeeding induces less weight gain during the first two years of life, which predicts less obesity up to adulthood. We tested the hypothesis that a high infant protein supply promotes weight gain and obesity risk, mediated by increased plasma amino acids and growth factors, insulin and insulin like growth factor 1 (IGF-1). A large multi-centre double blind trial randomized formula-fed infants to conventional bottle milk with a high protein content, or an intervention formula with a reduced protein content more similar to levels provided with human milk. Protein-reduced formula normalized weight, body mass index and body fatness up to 6 years, relative to a breastfed reference group, and reduced the adjusted odds for obesity 2.6-fold. Available data indicate potential underlying mechanisms. We conclude that infant feeding has very marked long-term programming effects on later BMI, obesity and adiposity, with major public health implications. Breastfeeding lowers the risk for later obesity and adiposity. This provides additional motivation for proactively and enthusiastically promoting, protecting and supporting breastfeeding. A high milk protein intake in infancy increases the long-term risk for obesity and adiposity. Infants not or not fully breastfed should receive infant formula delivering protein in amounts more similar to human milk contents, with high protein quality. Other sources of very high infant protein intakes, particular drinking unmodified cows' milk, should be avoided in infancy.
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Improved lung function at age 6 in children born very preterm and fed extra protein post-discharge.
Toftlund, LH, Agertoft, L, Halken, S, Zachariassen, G
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019;(1):47-54
Abstract
BACKGROUND In very preterm-born children, alveolar maturation is challenged and lung function is often compromised during childhood. So far, very few studies have focused on type of early nutrition and lung function in children born preterm. METHODS This study is a 6 years follow-up of 281 very preterm-born infants (VPI) with a gestational age (GA) <32 + 0 weeks. Infants breastfed at discharge from hospital were randomized to unfortified (UHM) or fortified (FHM) mother's (human) milk, whereas those not breastfed received a preterm formula (PF). The intervention lasted until 4 months corrected age. At 6 years of age fractional exhaled nitric oxide (FeNO), airway resistance and occlusion measurements with reversibility were performed. Data on predisposition to asthma and allergy as well as possible allergic symptoms of the child were obtained with questionnaires. RESULTS Outcome data was fully or partially available on 160 (66.9%) of 239 children. This included 49 (30.6%) children fed UHM, 58 (36.3%) fed FHM and 53 (33.1%) fed PF. Successful FeNO measurements were obtained in 119 (74.4%) children and airway resistance measurements in 160. FeNO results were not significantly different between feeding groups. Children fed a protein-enriched diet (FMH/PF) had the lowest, for example, best, airway resistance; FHM-fed had lower values than UHM-fed (P = 0.042) before, and PF-fed had significantly lower values than UHM-fed after beta-2-agonist inhalation (P = 0.050). The tendency of lower airway resistance when protein enriched were the same in gender-specific analyses. In SGA children, the same tendency was found between PF- and UHM-fed (P = 0.007 before and P = 0.046 after beta-2-agonist inhalation). All values were within reference limits. CONCLUSIONS Lung function in very preterm-born children may improve when fed a protein-enriched nutrition post-discharge.
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The role of long chain polyunsaturated fatty acids in perinatal nutrition.
Collins, CT, Gibson, RA, McPhee, AJ, Makrides, M
Seminars in perinatology. 2019;(7):151156
Abstract
The importance of omega-3 long chain polyunsaturated fatty acids in the perinatal period has been the focus of research for several decades. Infants born preterm miss out on the last trimester in utero transfer of omega-3 fatty acids and consequently have lower blood levels than infants born at term. Preterm infant formula was supplemented with the omega-3 docosahexaenoic acid and the omega-6 arachidonic acid from 2000 (to the level found in the breast milk of women consuming a western diet) based on trials reporting improvements in visual acuity. Docosahexaenoic acid supplementation beyond this level has not shown improvements in clinical or developmental outcomes, however the effect on childhood development in the most preterm infants remains to be resolved. Maternal omega-3 supplementation during pregnancy has the potential to reduce the incidence of preterm birth but may also, in some pregnancies, prolong gestation beyond term and increase fetal size.
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Conditional cash transfer and/or lipid-based nutrient supplement targeting the first 1000 d of life increased attendance at preventive care services but did not improve linear growth in young children in rural Mali: results of a cluster-randomized controlled trial.
Adubra, L, Le Port, A, Kameli, Y, Fortin, S, Mahamadou, T, Ruel, MT, Martin-Prevel, Y, Savy, M
The American journal of clinical nutrition. 2019;(6):1476-1490
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Abstract
BACKGROUND In 2014, the World Food Programme added to an ongoing health and nutrition program named "Santé Nutritionnelle à Assise Communautaire dans la région de Kayes" (SNACK), the distribution of cash to mothers and/or lipid-based nutrient supplement (LNS) to children aged 6-23 mo, conditional upon attendance at community health centers (CHCs) during the first 1000 d of life. OBJECTIVE We evaluated the additional impact of the distribution of cash and/or LNS on mean height-for-age z scores (HAZ; primary outcome), stunting (HAZ < -2), and on intermediate outcomes along the program impact pathways. METHODS In a cluster-randomized controlled trial using a 2 × 2 factorial design, 76 CHCs were randomly assigned to deliver either SNACK, SNACK + Cash, SNACK + LNS, or SNACK + Cash + LNS. Cross-sectional surveys among 12- to 42-mo-old children and their mothers were conducted at baseline (2013, n = 5046) and at endline (2016, n = 5098). RESULTS Factorial analysis showed no interaction between cash and LNS treatments for HAZ, but found an antagonistic interaction for stunting (OR: 1.55; 95% CI: 1.05, 2.31; P = 0.03). There were no impacts of the cash, LNS, or cash + LNS treatments, compared with the SNACK alone, on either HAZ or stunting (treatment × time interaction). There were significant impacts of the LNS and cash + LNS treatments on attendance at ≥1 growth monitoring (GM) session (OR: 3.95; 95% CI: 1.69, 9.24; OR: 3.90; 95% CI: 1.73, 8.81, respectively) and half the expected sessions (OR: 4.72; 95% CI: 1.47, 15.17; OR: 5.25; 95% CI: 1.82, 15.11, respectively), mothers' knowledge on importance of GM (OR: 1.98; 95% CI: 1.16, 3.39; OR: 3.12; 95% CI: 1.60, 6.09, respectively), and, only for the LNS group, appropriate timing for complementary feeding (OR: 1.62; 95% CI: 1.09, 2.41). CONCLUSIONS Implementation constraints and suboptimal participation in program activities may explain the lack of impact on child linear growth in this rural region of Mali.This trial was registered at www.isrctn.com as ISRCTN08435964.
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Nutritional policies for late preterm and early term infants - can we do better?
Muelbert, M, Harding, JE, Bloomfield, FH
Seminars in fetal & neonatal medicine. 2019;(1):43-47
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Abstract
Late preterm (LP) and early term (ET) infants can be considered the "great dissemblers": they resemble healthy full-term infants in appearance, but their immaturity places them at increased risk of poor short- and long-term outcomes. Nutritional requirements are greater than for full-term babies, but there are few good data on the nutritional requirements for LP and ET babies, leading to substantial variation in practice. Recent data indicate that rapid growth may be beneficial for neurocognitive function but not for body composition and later metabolic health. Breastfeeding the LP or ET infant can be challenging, and mothers of these infants may need additional support to breastfeed successfully. Future research should investigate nutritional requirements of LP and ET infants for optimal growth, addressing both short- and long-term outcomes and the potential trade-off between neurocognitive and metabolic benefits.
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10.
Formula versus maternal breast milk for feeding preterm or low birth weight infants.
Brown, JVE, Walsh, V, McGuire, W
The Cochrane database of systematic reviews. 2019;(8):CD002972
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BACKGROUND Artificial formula can be manipulated to contain higher amounts of macro-nutrients than maternal breast milk but breast milk confers important immuno-nutritional advantages for preterm or low birth weight (LBW) infants. OBJECTIVES To determine the effect of feeding preterm or LBW infants with formula compared with maternal breast milk on growth and developmental outcomes. SEARCH METHODS We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9), and Ovid MEDLINE, Ovid Embase, Ovid Maternity & Infant Care Database, and CINAHL to October 2018. We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles. SELECTION CRITERIA Randomised or quasi-randomised controlled trials that compared feeding preterm or low birth weight infants with formula versus maternal breast milk. DATA COLLECTION AND ANALYSIS Two review authors planned independently to assess trial eligibility and risk of bias, and extract data. We planned to analyse treatment effects as described in the individual trials and report risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with 95% confidence intervals. We planned to use a fixed-effect model in meta-analyses and to explore potential causes of heterogeneity in subgroup analyses. We planned to use the GRADE approach to assess the certainty of evidence. MAIN RESULTS We did not identify any eligible trials. AUTHORS' CONCLUSIONS There are no trials of formula versus maternal breast milk for feeding preterm or low birth weight infants. Such trials are unlikely to be conducted because of the difficulty of allocating an alternative form of nutrition to an infant whose mother wishes to feed with her own breast milk. Maternal breast milk remains the default choice of enteral nutrition because observational studies, and meta-analyses of trials comparing feeding with formula versus donor breast milk, suggest that feeding with breast milk has major immuno-nutritional advantages for preterm or low birth weight infants.