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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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Is the body composition development in premature infants associated with a distinctive nuclear magnetic resonance metabolomic profiling of urine?
Morniroli, D, Dessì, A, Giannì, ML, Roggero, P, Noto, A, Atzori, L, Lussu, M, Fanos, V, Mosca, F
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(14):2310-2318
Abstract
OBJECTIVE Preterm infants' body composition at term-corrected age differs from that of term infants but appears to be similar at the age of 3 months. The aim of this study was to compare the metabolomic pattern of preterm infants at term and at 3 months with that of term infants and to determine its association with body composition development. METHOD We designed a pilot study. Growth and body composition were evaluated by an air displacement plethysmography system in 13 preterm infants and seven term newborns at term and at 3 months of corrected age. Urine samples were collected at the same time points and analysed by nuclear magnetic resonance. RESULTS At term-corrected age, preterm infants showed a higher fat mass percentage compared with that of term newborns, whereas at 3 months of corrected age, the body composition parameters were similar between the groups. At the first time point, nuclear magnetic resonance analysis showed a urinary increase in choline/phosphocholine, betaine and glucose in preterm infants. At the second time point, the preterm group exhibited a urinary increase in choline/phosphocholine and a decrease in betaine. CONCLUSIONS The increased urinary excretion of choline, a betaine precursor, could reflect a potential altered metabolism in preterm infants.
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Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences.
Chinoy, A, Mughal, MZ, Padidela, R
Archives of disease in childhood. Fetal and neonatal edition. 2019;(5):F560-F566
Abstract
Metabolic bone disease of prematurity (MBDP) is characterised by skeletal demineralisation, and in severe cases it can result in fragility fractures of long bones and ribs during routine handling. MBDP arises from prenatal and postnatal factors. Infants who are born preterm are deprived of fetal mineral accumulation, 80% of which occurs in the third trimester. Postnatally, it is difficult to maintain a comparable intake of minerals, and medications, such as corticosteroids and diuretic therapy, lead to bone resorption. With improvements in neonatal care and nutrition, the incidence of MBDP in preterm infants appears to have decreased, although the recent practice of administering phosphate supplements alone will result in secondary hyperparathyroidism and associated bone loss, worsening MBDP. Postnatal immobilisation and loss of placental supply of oestrogen also contribute to skeletal demineralisation. There is no single diagnostic or screening test for MBDP, with pitfalls existing for most radiological and biochemical investigations. By reviewing the pathophysiology of calcium and phosphate homeostasis, one can establish that plasma parathyroid hormone is important in determining the aetiology of MBDP - primarily calcipaenia or phosphopaenia. This will then direct treatment with the appropriate supplements while considering optimal physiological calcium to phosphate ratios.
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Plasma Citrulline Concentrations in Neonates With or Without Gastrointestinal Disease During Periods of Parenteral and Enteral Nutrition.
Herrera, OR, Talati, AJ, Helms, RA
JPEN. Journal of parenteral and enteral nutrition. 2019;(8):977-985
Abstract
INTRODUCTION Citrulline is synthesized primarily in enterocytes. Retrospective work revealed higher plasma concentrations in patients without gastrointestinal (GI) disease than in those with GI disease, regardless of bowel resection, leading us to speculate whether it could be used as a marker of gut function prospectively. Our purpose was to analyze plasma citrulline in these patients, comparing a period of exclusive parenteral nutrition (PN) vs both PN and enteral nutrition (PN/EN). METHODS Premature neonates were included in this study. Plasma samples were collected during 2 periods, PN and PN/EN. They were classified into groups: patients without GI disease (Group 1), patients with GI disease without resection (Group 2), and patients with GI disease and resection (Group 3). Plasma was analyzed by high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Data were described as median with ranges. RESULTS Fifty patients were recruited for this study, from which 164 samples were obtained and analyzed by LC-MS. Median plasma citrulline concentrations were 12.3 (5.6-39.4) µmol/L, 14.9 (6.8-39.8) µmol/L, and 10.8 (2.0-23.6) µmol/L for Groups 1, 2, and 3, respectively. After Bonferroni correction, only Group 3 had a significantly different median from the others. No differences were observed within periods of nutrition (PN vs PN/EN). Postconceptual age (PCA), among others, was assessed to determine differences for which the former demonstrated significance. CONCLUSION Premature neonates with bowel resection had lower plasma citrulline concentrations, confirming its role as gut mass marker, though without differences during transitional feeding. PCA may affect expression of this protein.
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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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Human milk protein vs. formula protein and their use in preterm infants.
Gianni, ML, Roggero, P, Mosca, F
Current opinion in clinical nutrition and metabolic care. 2019;(1):76-81
Abstract
PURPOSE OF REVIEW We review the current available evidence on the metabolic fate of human milk proteins and their potential clinical implications for growth and body composition development vs. those of formula proteins in preterm infants. RECENT FINDINGS The decreased content of human milk protein in preterm mothers throughout lactation might contribute to the reduced growth reported in exclusively human milk-fed infants compared with that of formula-fed infants. Recent studies have demonstrated that preterm infants are capable of degrading human milk proteins regardless of their degree of prematurity or postnatal age, with limited contribution from milk proteases to protein digestion. The nitrogen balance of fortified human milk-fed preterm infants is higher than that of formula-fed preterm infants. Moreover, the growth of human milk-fed preterm infants appears to be accompanied by fat-free mass deposition. SUMMARY Provided that adequate protein and energy intakes are delivered, human milk enhances protein use rather than oxidation as well as promotes tissue growth, leading to preferential fat-free mass deposition and contributing to the recovery of the body composition in preterm infants. Human milk feeding should be supported and promoted for all preterm mother-infant pairs.
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The effects of kangaroo mother care on the time to breastfeeding initiation among preterm and LBW infants: a meta-analysis of published studies.
Mekonnen, AG, Yehualashet, SS, Bayleyegn, AD
International breastfeeding journal. 2019;:12
Abstract
BACKGROUND Kangaroo mother care is a comprehensive intervention given for all newborns especially for premature and low birthweight infants. It is the most feasible and preferred intervention for decreasing neonatal morbidity and mortality. Even though time to initiating breastfeeding has been examined by randomized controlled trials, varying findings have been reported. Therefore, the main objective of this meta-analysis was to estimate the pooled mean time to initiate breastfeeding among preterm and low birthweight infants. METHODS The authors searched for randomized controlled trial studies conducted on the effects of kangaroo mother care on the time to breastfeeding initiation among preterm and low birthweight infants. Published articles were identified through a computerized search of electronic databases that includes MEDLINE via PubMed, EMBASE, CINAHL and CENTRAL. The search terms were kangaroo mother care or (skin to skin), or conventional care, newborns, preterm infants, low birthweight infants and randomized controlled trial. A total of 467 eligible titles were identified and eight studies met the inclusion criteria. The extracted data were entered and analyzed using Cochrane Review Manager-5-3 software. Heterogeneity across studies was evaluated by Chi2 test and inconsistency index (I2). Publication bias was assessed using a funnel plot. The random effect model was applied to estimate the pooled mean time to initiate breastfeeding with 95% confidence interval. RESULTS In this meta-analysis, the overall pooled mean time to initiate breastfeeding was 2.6 days (95% CI 1.23, 3.96). Preterm and low birthweight infants receiving kangaroo mother care intervention initiated breastfeeding 2 days 14 h 24 min earlier than conventional care of radiant warmer/incubator method. CONCLUSIONS Kangaroo mother care promotes early initiation of breastfeeding as compared to conventional care method. Therefore, health facilities need to implement the kangaroo mother care for preterm and low birthweight infants.
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Antenatal Magnesium Sulfate Exposure and Ponderal Index in Preterm Infants.
Deihl, TE, Simhan, HN
American journal of perinatology. 2019;(3):329-334
Abstract
OBJECTIVE Antenatal magnesium sulfate (MgSO4) is known to affect the central nervous system of preterm infants, and there is biologic rationale for influence on other phenotypes. This study investigated the effect of MgSO4 exposure on the trajectory of ponderal index (PI, kg/m3) from birth to 2 years of age. STUDY DESIGN A secondary analysis of a U.S. randomized controlled trial investigating MgSO4 versus placebo administration among women at high risk for preterm delivery was performed. Multivariable logistic regression was used to assess the relationship between PI from birth to 2 years of age and exposure to MgSO4 versus placebo. RESULTS There was a larger decrement in PI from birth to 2 years of age in infants exposed to MgSO4 compared with placebo (p = 0.032). There was a statistically significant one-way interaction between newborn sex and treatment group (p = 0.019). Change in PI in males exhibited a greater decrement in those exposed to MgSO4 versus placebo (p = 0.227), whereas female infants exposed to MgSO4 had a smaller decrement (p = 0.04). CONCLUSION MgSO4 exposure in preterm infants is associated with a larger decrease in PI from birth to 2 years of age. In addition, the direction of effect of MgSO4 on the change in PI over the first 2 years of life is different by sex.
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Choline and choline-related nutrients in regular and preterm infant growth.
Bernhard, W, Poets, CF, Franz, AR
European journal of nutrition. 2019;(3):931-945
Abstract
BACKGROUND Choline is an essential nutrient, with increased requirements during development. It forms the headgroup of phosphatidylcholine and sphingomyelin in all membranes and many secretions. Phosphatidylcholine is linked to cell signaling as a phosphocholine donor to synthesize sphingomyelin from ceramide, a trigger of apoptosis, and is the major carrier of arachidonic and docosahexaenoic acid in plasma. Acetylcholine is important for neurodevelopment and the placental storage form for fetal choline supply. Betaine, a choline metabolite, functions as osmolyte and methyl donor. Their concentrations are all tightly regulated in tissues. CLINCAL IMPACT During the fetal growth spurt at 24-34-week postmenstrual age, plasma choline is higher than beyond 34 weeks, and threefold higher than in pregnant women [45 (36-60) µmol/L vs. 14 (10-17) µmol/L]. The rapid decrease in plasma choline after premature birth suggests an untimely reduction in choline supply, as cellular uptake is proportional to plasma concentration. Supply via breast milk, with phosphocholine and α-glycerophosphocholine as its major choline components, does not prevent such postnatal decrease. Moreover, high amounts of liver PC are secreted via bile, causing rapid hepatic choline turnover via the enterohepatic cycle, and deficiency in case of pancreatic phospholipase A2 deficiency or intestinal resection. Choline deficiency causes hepatic damage and choline accretion at the expense of the lungs and other tissues. CONCLUSION Choline deficiency may contribute to the impaired lean body mass growth and pulmonary and neurocognitive development of preterm infants despite adequate macronutrient supply and weight gain. In this context, a reconsideration of current recommendations for choline supply to preterm infants is required.
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A Review of Bioactive Factors in Human Breastmilk: A Focus on Prematurity.
Gila-Diaz, A, Arribas, SM, Algara, A, Martín-Cabrejas, MA, López de Pablo, ÁL, Sáenz de Pipaón, M, Ramiro-Cortijo, D
Nutrients. 2019;(6)
Abstract
Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.