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Milk Fat Globule Membrane Supplementation in Children: Systematic Review with Meta-Analysis.
Ambrożej, D, Dumycz, K, Dziechciarz, P, Ruszczyński, M
Nutrients. 2021;(3)
Abstract
(1) Background: Milk fat globule membrane (MFGM), composing fat droplets responsible for lipid transport in breast milk, has been shown to possess immunological and antimicrobial effects. Standard formulas (SF) are devoid of MFGMs during the production process. The study's aim was to evaluate the safety and benefits of MFGMs supplementation in children. (2) Methods: We searched four databases for randomized controlled trials evaluating the supplementation of MFGMs in children. Growth parameters were chosen as the primary outcome. (3) Results: Twenty-four publications of seventeen studies were included. Meta-analyses assessing the primary outcomes at the age of 4 months included four studies (814 children) comparing the MFGM-supplemented formulas and SF, and two trials (549 children) comparing the MFGM-supplemented formulas and breastfeeding. The primary outcomes were non-inferior in all the experimental MFGM formulas compared to SF, or even represented more similar results to breastfed infants. The promising effects, including a lower incidence of acute otitis media and improved cognitive development, cannot be firmly confirmed due to the small amount of existing evidence. No significant adverse effects were reported in any of the assessed products. (4) Conclusions: The available data signaled beneficial effects and a good safety profile, requiring future research with well-designed trials.
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Effect of long-chain polyunsaturated fatty acids in infant formula on long-term cognitive function in childhood: A systematic review and meta-analysis of randomised controlled trials.
Verfuerden, ML, Dib, S, Jerrim, J, Fewtrell, M, Gilbert, RE
PloS one. 2020;(11):e0241800
Abstract
PROSPERO registration numbers CRD42018105196 and CRD42018088868.
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3.
Comparison of different protein concentrations of human milk fortifier for promoting growth and neurological development in preterm infants.
Gao, C, Miller, J, Collins, CT, Rumbold, AR
The Cochrane database of systematic reviews. 2020;(11):CD007090
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Abstract
BACKGROUND Human milk alone may provide inadequate amounts of protein to meet the growth requirements of preterm infants because of restrictions in the amount of fluid they can tolerate. It has become common practice to feed preterm infants with breast milk fortified with protein and other nutrients but there is debate about the optimal concentration of protein in commercially available fortifiers. OBJECTIVES To compare the effects of different protein concentrations in human milk fortifier, fed to preterm infants, on growth and neurodevelopment. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 8), Ovid MEDLINE and CINAHL on 15 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA We included all published and unpublished randomised, quasi-randomised and cluster-randomised trials comparing two different concentrations of protein in human milk fortifier. We included preterm infants (less than 37 weeks' gestational age). Participants may have been exclusively fed human milk or have been supplemented with formula. The concentration of protein was classified as low (< 1g protein/100 mL expressed breast milk (EBM)), moderate (≥ 1g to < 1.4g protein/100 mL EBM) or high (≥ 1.4g protein/100 mL EBM). We excluded trials that compared two protein concentrations that fell within the same category. DATA COLLECTION AND ANALYSIS We undertook data collection and analyses using the standard methods of Cochrane Neonatal. Two review authors independently evaluated trials. Primary outcomes included growth, neurodevelopmental outcome and mortality. Data were synthesised using risk ratios (RR), risk differences and mean differences (MD), with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS We identified nine trials involving 861 infants. There is one trial awaiting classification, and nine ongoing trials. The trials were mostly conducted in infants born < 32 weeks' gestational age or < 1500 g birthweight, or both. All used a fortifier derived from bovine milk. Two trials fed infants exclusively with mother's own milk, three trials gave supplementary feeds with donor human milk and four trials supplemented with preterm infant formula. Overall, trials were small but generally at low or unclear risk of bias. High versus moderate protein concentration of human milk fortifier There was moderate certainty evidence that a high protein concentration likely increased in-hospital weight gain compared to moderate concentration of human milk fortifier (MD 0.66 g/kg/day, 95% CI 0.51 to 0.82; trials = 6, participants = 606). The evidence was very uncertain about the effect of high versus moderate protein concentration on length gain (MD 0.01 cm/week, 95% CI -0.01 to 0.03; trials = 5, participants = 547; very low certainty evidence) and head circumference gain (MD 0.00 cm/week, 95% CI -0.01 to 0.02; trials = 5, participants = 549; very low certainty evidence). Only one trial reported neonatal mortality, with no deaths in either group (participants = 45). Moderate versus low protein concentration of human milk fortifier A moderate versus low protein concentration fortifier may increase weight gain (MD 2.08 g/kg/day, 95% CI 0.38 to 3.77; trials = 2, participants = 176; very low certainty evidence) with little to no effect on head circumference gain (MD 0.13 cm/week, 95% CI 0.00 to 0.26; I² = 85%; trials = 3, participants = 217; very low certainty evidence), but the evidence is very uncertain. There was low certainty evidence that a moderate protein concentration may increase length gain (MD 0.09 cm/week, 95% CI 0.05 to 0.14; trials = 3, participants = 217). Only one trial reported mortality and found no difference between groups (RR 0.48, 95% CI 0.05 to 5.17; participants = 112). No trials reported long term growth or neurodevelopmental outcomes including cerebral palsy and developmental delay. AUTHORS' CONCLUSIONS Feeding preterm infants with a human milk fortifier containing high amounts of protein (≥ 1.4g/100 mL EBM) compared with a fortifier containing moderate protein concentration (≥ 1 g to < 1.4 g/100 mL EBM) results in small increases in weight gain during the neonatal admission. There may also be small increases in weight and length gain when infants are fed a fortifier containing moderate versus low protein concentration (< 1 g protein/100 mL EBM). The certainty of this evidence is very low to moderate; therefore, results may change when the findings of ongoing studies are available. There is insufficient evidence to assess the impact of protein concentration on adverse effects or long term outcomes such as neurodevelopment. Further trials are needed to determine whether modest increases in weight gain observed with higher protein concentration fortifiers are associated with benefits or harms to long term growth and neurodevelopment.
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Higher versus lower protein intake in formula-fed low birth weight infants.
Fenton, TR, Al-Wassia, H, Premji, SS, Sauve, RS
The Cochrane database of systematic reviews. 2020;(6):CD003959
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Abstract
BACKGROUND The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate. Protein intake must be sufficient to achieve normal growth without leading to negative effects such as acidosis, uremia, and elevated levels of circulating amino acids. OBJECTIVES To determine whether higher (≥ 3.0 g/kg/d) versus lower (< 3.0 g/kg/d) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants (< 2.5 kilograms) results in improved growth and neurodevelopmental outcomes without evidence of short- or long-term morbidity. Specific objectives were to examine the following comparisons of interventions and to conduct subgroup analyses if possible. 1. Low protein intake if the amount was less than 3.0 g/kg/d. 2. High protein intake if the amount was equal to or greater than 3.0 g/kg/d but less than 4.0 g/kg/d. 3. Very high protein intake if the amount was equal to or greater than 4.0 g/kg/d. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), in the Cochrane Library (August 2, 2019); OVID MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R) (to August 2, 2019); MEDLINE via PubMed (to August 2, 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (to August 2, 2019). We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA We included RCTs contrasting levels of formula protein intake as low (< 3.0 g/kg/d), high (≥ 3.0 g/kg/d but < 4.0 g/kg/d), or very high (≥ 4.0 g/kg/d) in formula-fed hospitalized neonates weighing less than 2.5 kilograms. We excluded studies if infants received partial parenteral nutrition during the study period, or if infants were fed formula as a supplement to human milk. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane and the GRADE approach to assess the certainty of evidence. MAIN RESULTS We identified six eligible trials that enrolled 218 infants through searches updated to August 2, 2019. Five studies compared low (< 3 g/kg/d) versus high (3.0 to 4.0 g/kg/d) protein intake using formulas that kept other nutrients constant. The trials were small (n = 139), and almost all had methodological limitations; the most frequent uncertainty was about attrition. Low-certainty evidence suggests improved weight gain (mean difference [MD] 2.36 g/kg/d, 95% confidence interval [CI] 1.31 to 3.40) and higher nitrogen accretion in infants receiving formula with higher protein content (3.0 to 4.0 g/kg/d) versus lower protein content (< 3 g/kg/d), while other nutrients were kept constant. No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea. We are uncertain whether high versus low protein intake affects head growth (MD 0.37 cm/week, 95% CI 0.16 to 0.58; n = 18) and length gain (MD 0.16 cm/week, 95% CI -0.02 to 0.34; n = 48), but sample sizes were small for these comparisons. One study compared high (3.0 to 4.0 g/kg/d) versus very high (≥ 4 g/kg/d) protein intake (average intakes were 3.6 and 4.1 g/kg/d) during and after an initial hospital stay (n = 77). Moderate-certainty evidence shows no significant differences in weight gain or length gain to discharge, term, and 12 weeks corrected age from very high protein intake (4.1 versus 3.6 g/kg/d). Three of the 24 infants receiving very high protein intake developed uremia. AUTHORS' CONCLUSIONS Higher protein intake (≥ 3.0 g/kg/d but < 4.0 g/kg/d) from formula accelerates weight gain. However, limited information is available regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopment. Research is needed to investigate the safety and effectiveness of protein intake ≥ 4.0 g/kg/d.
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Effects of dietary nucleotide supplementation on growth in infants: a meta-analysis of randomized controlled trials.
Wang, L, Mu, S, Xu, X, Shi, Z, Shen, L
European journal of nutrition. 2019;(3):1213-1221
Abstract
PURPOSE Dietary nucleotides are thought to be conditionally essential nutrients in infancy. However, studies have reported inconsistent findings regarding the association between nucleotide supplementation and infant physical growth. We conducted this meta-analysis to examine the efficacy of nucleotide supplementation of infant formula in promoting early infant growth. METHODS Randomized controlled trials that evaluated the association between nucleotide supplementation and infant growth through June 2017 were included. Study quality was assessed using the Cochrane Collaboration's Risk of Bias tool. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Q and I2 tests. RESULTS Nucleotide supplementation significantly increased the rate of weight gain (SMD 0.26; 95% CI 0.06-0.47), but had no effect on weight (SMD - 0.16; 95% CI - 0.55-0.23), weight Z score (SMD, - 0.42; 95% CI - 1.64-0.81), length (SMD 0.01; 95% CI - 0.18-0.21) and length Z score (SMD 0.15; 95% CI - 0.10-0.40). Occipitofrontal head circumference (OFC) at 7-8 weeks (SMD 0.30; 95% CI 0.10-0.50) and the rate of OFC gain (SMD 0.34; 95% CI 0.09-0.58) were significantly improved with nucleotide supplementation, whereas, 16- and 20-week OFC values did not differ. CONCLUSIONS Our meta-analysis indicated that nucleotide supplementation can increase the rate of weight gain, OFC and rate of OFC gain; however, we cannot conclude that it affects weight, weight Z score, length or length Z score. Large-scale randomized controlled trials of long-term nucleotide supplementation are needed to reach definitive conclusions.
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Is Donated Breast Milk Better Than Formula for Feeding Very Low Birth Weight Infants? A Systematic Review and Meta-Analysis.
Yu, F, Cao, B, Wen, Z, Li, M, Chen, H, Xie, G
Worldviews on evidence-based nursing. 2019;(6):485-494
Abstract
BACKGROUND The role of donated breast milk and formula feeding in very low birth weight infants (VLBWIs) remains unclear. OBJECTIVE The objective for this study was to evaluate the efficacy and safety of breast milk and formula for feeding VLBWIs. METHODS A comprehensive search of PubMed databases was conducted on November 30, 2018, to identify related randomized controlled trials (RCTs). Pooled odds ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using either a fixed or random-effects model. RESULTS Seven RCTs with a total of 876 infants were included. The formula showed more advantages in increasing infant weight (MD = -6.58, 95% CI: -11.19 to -1.98) and length (MD = -0.30, 95% CI: -0.41 to -0.20) than donated breast milk, but formula could also significantly increase the risks of necrotizing enterocolitis (OR = 0.33, 95% CI: 0.18 to 0.59) and length of hospital stay (MD = -3.78, 95% CI: -6.84 to -0.72) when compared with donated breast milk. No significant differences on the head circumference gain (MD = -0.16, 95% CI: -0.33 to 0.01), sepsis (OR = 1.21, 95% CI: 0.84 to 1.75), retinopathy of prematurity (OR = 1.22, 95% CI: 0.73 to 2.05) and mortality (OR = 0.84, 95% CI: 0.47 to 1.52) were found. LINKING EVIDENCE TO ACTION The donated breast milk shows more advantages in reducing the incidence of NEC and length of hospital stay, but also more disadvantages in increasing the weight and length of VLBWIs and ELBWIs when compared with preterm formula feeding. Currently, there is no solid evidence demonstrating a significant advantage of donated breast milk over formula in the feeding of VLBWIs. Larger-scale RCTs with rigorous designs are needed to elucidate the feeding plans of VLBWIs.