The influence of a maternal vegan diet on carnitine and vitamin B2 concentrations in human milk.

Background: The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the nutritional adequacy of their milk. Two important nutrients, vitamin B2 and carnitine, are mostly ingested via animal products. Objective: We investigated the influence of a vegan diet on the vitamin B2 and carnitine concentrations in milk and serum of lactating women. Methods: In this case-control study, 25 lactating mothers following an exclusive vegan diet were comparted to 25 healthy lactating mothers with an omnivorous diet without use of supplements. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to measure vitamin B2 and carnitine concentrations, respectively. A linear regression model was used to determine differences in human milk and serum concentrations between study groups. Results: Vitamin B2 concentrations in human milk and serum did not differ between study groups. While the human milk free carnitine (C0) and acetyl carnitine (C2) concentrations did not differ between study groups, serum carnitine concentrations were lower in participants following a vegan diet than in omnivorous women (p < 0.0001). Conclusion: A maternal vegan diet did not affect human milk concentration of vitamin B2 and carnitine. Breastfed infants of mothers following an exclusive vegan diet therefore are likely not at increased risk of developing a vitamin B2 or carnitine deficiency.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review.

Feeding preterm infants with mother's own milk is associated with a reduction in postnatal complications and an improved neurocognitive outcome. Therefore, the bioactive factor composition of human milk has been used as a tool for the development of nutritional supplements with a potential prophylactic or therapeutic effect. The aim of this systematic review was to provide an overview on bioactive factors which have been studied as supplement to enteral nutrition in randomized controlled trials, and to provide an overview of ongoing trials. MEDLINE, EMBASE, CENTRAL, and clinical trial registers were searched. Studies on the antimicrobial protein lactoferrin were excluded as these were summarized very recently in three separate systematic reviews. Studies on vitamins D, K and iron were also excluded as they are already incorporated in most international guidelines. We identified 17 different bioactive factors, which were investigated in 26 studies. Despite the encouraging potential effects of several bioactive factors, more high-quality studies with a sufficient number of preterm infants are required before a certain factor may be implemented into clinical practice. Three large trials (n > 500) that investigate the effects of either enteral insulin or vitamin A are currently ongoing and could provide more definite answers on these specific supplements.

Protein intakes to optimize outcomes for preterm infants.

Proteins are key structural components of all human cells and are also involved in key physiologic processes through their roles as enzymes, hormones and transport proteins. Protein requirements are substantially higher in preterm infants than those born at term, yet inadequate protein intakes are a common problem on many neonatal units. Very preterm infants (VPT, <32 weeks) commonly receive parenteral amino acid solutions which are typically commenced on admission, and increased over the next few days. Several recent studies have explored differing parenteral amino acid intakes in the first few days, and recommendations have recently been updated. Parenteral nutrition intakes are decreased as enteral feeds are tolerated, but human milk alone will not meet protein needs in most VPT and supplementation or fortification will be required. This review paper considers basic protein and amino acid physiology in the newborn period, and the evidence base for current recommendations.

Nutrient Fortification of Human Donor Milk Affects Intestinal Function and Protein Metabolism in Preterm Pigs.

Background: Nutrient fortification of human milk is often required to secure adequate growth and organ development for very preterm infants. There is concern that formula-based fortifiers (FFs) induce intestinal dysfunction, feeding intolerance, and necrotizing enterocolitis (NEC). Bovine colostrum (BC) may be an alternative nutrient fortifier, considering its high content of protein and milk bioactive factors. Objective: We investigated whether BC was superior to an FF product based on processed bovine milk and vegetable oil to fortify donor human milk (DHM) for preterm pigs, used as a model for infants. Methods: Sixty preterm pigs from 4 sows (Danish Landrace × Large White × Duroc, birth weight 944 ± 29 g) received decreasing volumes of parenteral nutrition (96-72 mL â‹… kg-1 â‹… d-1) and increasing volumes of enteral nutrition (24-132 mL â‹… kg-1 â‹… d-1) for 8 d. Pigs were fed donor porcine milk (DPM) and DHM with or without FF or BC fortification (+4.6 g protein â‹… kg-1 â‹… d-1). Results: DPM-fed pigs showed higher growth (10-fold), protein synthesis (+15-30%), villus heights, lactase and peptidase activities (+30%), and reduced intestinal cytokines (-50%) relative to DHM pigs (all P < 0.05). Fortification increased protein synthesis (+20-30%), but with higher weight gain and lower urea and cortisol concentrations for DHM+BC compared with DHM+FF pigs (2- to 3-fold differences, all P ≤ 0.06). DHM+FF pigs showed more diarrhea and reduced lactase and peptidase activities, hexose uptake, and villus heights relative to DHM+BC or DHM pigs (30-90% differences, P < 0.05). Fortification did not affect NEC incidence but DHM+BC pigs had lower colonic interleukin (IL)-6 and IL-8 concentrations relative to the remaining pigs (-30%, P = 0.06). DHM+FF pigs had higher stomach bacterial load than did DHM, and higher bacterial density along intestinal villi than did DHM and DHM+BC pigs (2- to 3-fold, P < 0.05). Conclusions: The FF product investigated in this study reduced growth, intestinal function, and protein utilization in DHM-fed preterm pigs, relative to BC as fortifier. The relevance of BC as an alternative nutrient fortifier for preterm infants should be tested.

Two-Year Follow-up of a Randomized Controlled Nutrition Intervention Trial in Very Low-Birth-Weight Infants.

BACKGROUND: Very low-birth-weight (VLBW) infants are at risk for neurodevelopment impairment. This study assessed the effect of early aggressive parenteral nutrition (PN) on long-term outcome in VLBW infants. MATERIALS AND METHODS: Directly after birth, VLBW infants (birth weight <1500 g, n = 142) were randomized to 5 different PN regimes. Controls (n = 46) received glucose and standard-dose amino acids (AAs; 2.4 g/[kg·d]) from birth onward and pure soybean oil fat emulsion (SOY) on the second day of life. Two intervention groups received glucose, standard-dose AAs, and lipids from birth onward: SOY (n = 24) or mixed fat emulsion (MIX, n = 25). The 2 other intervention groups received glucose, high-dose AAs (3.6 g/[kg·d]), and lipids from birth onward: SOY (n = 24) or MIX (n = 23). The primary outcome of this follow-up study was the composite outcome of "death or major disability" at 2 years corrected age. Secondary outcomes were death, major disabilities, neurodevelopmental scores, and anthropometry. RESULTS: Follow-up rate was 92% (n = 134). Thirty-five (26%) infants had died or had a major disability, with no differences between intervention groups and controls. Increased odds for death were observed in the standard-dose AA-MIX group (odds ratio, 5.4; 95% confidence interval [CI], 1.1-27.0). Neurodevelopmental scores and incidence of major disabilities did not differ between groups. Growth in the high-dose AA-MIX group was enhanced compared with growth in controls at 2 years corrected age (+0.51 [0.01-1.02] weight SDS). CONCLUSION: This randomized controlled hypothesis-generating study demonstrated no beneficial effect of early high-dose AA administration and mixed fat emulsions on survival and neurodevelopmental outcome in VLBW infants, although growth was enhanced.

Defining Protein Requirements of Preterm Infants by Using Metabolic Studies in Fetuses and Preterm Infants.

Amino acids form one of the main building blocks for fetal and neonatal growth. Despite improvements in neonatal care, including postnatal nutrition, growth faltering and suboptimal outcome after premature birth are still frequently encountered. Nutrition can partly be held responsible. Over the years, there has been a trend in delivering amino acids earlier from birth on and in larger quantities. Unfortunately, little is known about the specific metabolism of proteins, especially during fetal life or during disease. This review gives an overview of different methods of studying metabolism during early life and what we have come to learn so far. Different examples are given on the complex interplay between the placenta and the fetus. From both ovine and human studies, we know that amino acids are not only used for protein synthesis in the fetus, they are also oxidized to a large extent. Postnatally, we have succeeded in improving the nitrogen balance in preterm infants, but the preconditions need also to be improved before concluding that today's policy is optimal. Only by gaining more knowledge on both fetal and neonatal physiology and disease will we be able to further optimize growth and functional outcome in premature infants.

Albumin synthesis in very low birth weight infants is enhanced by early parenteral lipid and high-dose amino acid administration.

BACKGROUND & AIMS: Albumin is one of the most important plasma proteins and plays a key role in many physiologic processes, such as preserving colloid osmotic pressure, scavenging radicals, and binding and transporting bilirubin, hormones, and drugs. However, albumin concentrations are often low in preterm infants during the first days of life. We hypothesized that early parenteral lipid and high-dose amino acid (AA) administration to very low birth weight (VLBW) infants from birth onwards increases hepatic albumin synthesis rates. METHODS: Inborn VLBW infants were randomized to receive from birth onwards either 2.4 g amino acids/(kg(·)d) (control group), 2.4 g amino acids/(kg(·)d) plus 2 g lipids/(kg(·)d) (AA + lipid group), or 3.6 g amino acids/(kg(·)d) plus 2 g lipids/(kg(·)d) (high AA + lipid group). On postnatal day 2, infants received a primed continuous infusion of [U-(13)C6,(15)N]leucine. Mass spectrometry was used to determine the fractional and absolute albumin synthesis rates (FSR and ASR, respectively). RESULTS: In total, 28 infants (median gestational age 27 weeks (IQR 25-28), median birth weight 810 g (IQR 679-998) were studied. The median FSR was 6.5%/d in the control group, 10.6%/d in the AA group, and 12.3%/d in the high AA + lipid group, while the median was 84 mg/(kg(·)d) in the control group, 138 mg/(kg(·)d) in the AA group, and 160 mg/(kg(·)d) in the high AA + lipid group. CONCLUSION: A group of VLBW infants given parenteral nutrition containing lipids and high-dose amino acids showed a higher rate of albumin synthesis compared to infants receiving no lipids and standard amounts of amino acids during the first two days of life.

Observational outcome results following a randomized controlled trial of early amino acid administration in preterm infants.

OBJECTIVE: Several reports have investigated amino acid administration in premature infants during the early postnatal phase. Most of these previous studies, however, have only evaluated short-term in-hospital outcomes. Our aim was to describe long-term outcomes in premature infants previously subjected to different nutritional regimens in a randomized controlled trial. The primary outcome was survival without major disabilities, and the secondary outcomes included anthropometry and mental development. METHODS: Infants born <32 weeks' gestation and <1500 g were randomized to receive glucose (n = 69) or glucose with 2.4 g · kg(-1) · day(-1 amino acids) (n = 63) from birth. From postnatal day 3 onward, the nutritional intake was similar. At 2 years of corrected age, the surviving infants were assessed for neurodevelopmental outcome and anthropometry. RESULTS: Ninety-seven percent of the surviving infants were examined at follow-up, with no overall effect on survival without major disabilities. Boys, however, had a normal outcome significantly more often if amino acids were administered from birth onward (crude odds ratio 3.8, 95% confidence interval 1.3-11.4) and following adjustment for confounders (odds ratio 6.2, 95% confidence interval 1.0-38.0). The secondary outcomes exhibited no differences in anthropometric data. The mental developmental index was lower in the small number of girls who survived without major disabilities following the early administration of amino acids. CONCLUSIONS: In this hypothesis-generating outcome study, premature boys, but not girls, benefited from amino acid administration directly following birth. The observed lower mental developmental index in a subgroup of girls, however, warrants further studies.

Growth and fatty acid profiles of VLBW infants receiving a multicomponent lipid emulsion from birth.

OBJECTIVES: Very-low-birth-weight (VLBW) infants are dependent on parenteral nutrition after birth. A parenteral lipid emulsion with a multicomponent composition may improve growth and neurodevelopment and may prevent liver injury, which is often observed in association with long-term parenteral nutrition with pure soybean oil. Our aim was to evaluate the safety and efficacy of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triacylglycerol, 25% olive oil, and 15% fish oil compared with a conventional pure soybean oil emulsion in VLBW infants. METHODS: We conducted a double-blind randomized controlled trial in VLBW infants randomized to parenteral nutrition with the multicomponent (study group) or pure soybean oil emulsion (control group) from birth at a dose of 2 to 3 g · kg(-1) · day(-1) until the infants were receiving full enteral nutrition. We assessed efficacy by growth rates and measuring plasma fatty acid profiles (representative subset). Safety was evaluated by assessing hematologic and biochemical parameters, potentially harmful phytosterol concentrations (same subset), and clinical neonatal outcome parameters. RESULTS: Ninety-six infants were included (subsets n = 21). The multicomponent emulsion was associated with higher weight and head circumference z scores during admission. Plasma eicosapentaenoic acid and docosahexaenoic acid concentrations were higher in the study group. The hematological, biochemical, and neonatal outcomes were not different between groups, whereas the plasma concentrations of phytosterols were higher in the control group. CONCLUSIONS: The multicomponent lipid emulsion was well tolerated and associated with improved growth and higher plasma fatty acid profiles in VLBW infants in comparison with the pure soybean oil emulsion.

Adaptive regulation of amino acid metabolism on early parenteral lipid and high-dose amino acid administration in VLBW infants - a randomized, controlled trial.

BACKGROUND & AIMS: An anabolic state can be achieved upon intravenous amino acid administration during the immediate postnatal phase despite a low energy intake. The optimal dosing of amino acid and energy intake has yet to be established. The aim was to quantify the efficacy of early initiation of parenteral lipids and increased amounts of amino acids on metabolism and protein accretion in very low birth weight infants. METHODS: 28 very low birth weight infants were randomized to receive parenteral nutrition with glucose and either 2.4 g amino acids/(kg·d) (control group), 2.4 g amino acids/(kg·d) plus 2-3 g lipid/(kg·d) (AA + lipid group), or 3.6 g amino acids/(kg·d) plus 2-3 g lipid/(kg·d) (high AA + lipid group) from birth onward. On postnatal day 2, we performed a stable isotope study with [1-(13)C]phenylalanine, [ring-D4]tyrosine, [U-(13)C6,(15)N]leucine, and [methyl-D3]α-ketoisocaproic acid to quantify intermediate amino acid metabolism. RESULTS: The addition of lipids only had no effect on phenylalanine metabolism, whereas the addition of both lipids and additional amino acids increased the amount of phenylalanine used for protein synthesis. In addition, high amino acid intake significantly increased the rate of hydroxylation of phenylalanine to tyrosine, increasing the availability of tyrosine for protein synthesis. However, it also increased urea concentrations. Increasing energy intake from 40 to 60 kcal/(kg·d) did not increase protein efficiency as measured by phenylalanine kinetics. The leucine data were difficult to interpret due to the wide range of results and inconsistency in the data between the phenylalanine and leucine models. CONCLUSIONS: High amino acid and energy intakes from birth onwards result in a more anabolic state in very low birth weight infants, but at the expense of higher urea concentrations, which reflects a higher amino acid oxidation. Long-term outcome data should reveal whether this policy deserves routine implementation. This trial was registered at www.trialregister.nl, trial number NTR1445, name Nutritional Intervention for Preterm Infants-2.

Safety and efficacy of early parenteral lipid and high-dose amino acid administration to very low birth weight infants.

OBJECTIVE: To assess the efficacy and safety of early parenteral lipid and high-dose amino acid (AA) administration from birth onwards in very low birth weight (VLBW, birth weight <1500 g) infants. STUDY DESIGN: VLBW infants (n = 144; birth weight 862 ± 218 g; gestational age 27.4 ± 2.2 weeks) were randomized to receive 2.4 g of AA kg(-1) · d(-1) (control group), or 2.4 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (AA + lipid group), or 3.6 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (high AA + lipid group) from birth onwards. The primary outcome was nitrogen balance. The secondary outcomes were biochemical variables, urea rate of appearance, growth rates, and clinical outcome. RESULTS: The nitrogen balance on day 2 was significantly greater in both intervention groups compared with the control group. Greater amounts of AA administration did not further improve nitrogen balance compared with standard AA dose plus lipids and was associated with high plasma urea concentrations and high rates of urea appearance. No differences in other biochemical variables, growth, or clinical outcomes were observed. CONCLUSIONS: In VLBW infants, the administration of parenteral AA combined with lipids from birth onwards improved conditions for anabolism and growth, as shown by improved nitrogen balance. Greater levels of AA administration did not further improve the nitrogen balance but led to increased AA oxidation. Early lipid initiation and high-dose AA were well tolerated.

Parenteral lipid administration to very-low-birth-weight infants--early introduction of lipids and use of new lipid emulsions: a systematic review and meta-analysis.

BACKGROUND: The use of intravenous lipid emulsions in preterm infants has been limited by concerns regarding impaired lipid tolerance. As a result, the time of initiation of parenteral lipid infusion to very-low-birth-weight (VLBW) infants varies widely among different neonatal intensive care units. However, lipids provide energy for protein synthesis and supply essential fatty acids that are necessary for central nervous system development. OBJECTIVE: The objective was to summarize the effects of initiation of lipids within the first 2 d of life and the effects of different lipid compositions on growth and morbidities in VLBW infants. DESIGN: A systematic review and meta-analysis of publications identified in a search of PubMed, EMBASE, and Cochrane databases was undertaken. Randomized controlled studies were eligible if information on growth was available. RESULTS: The search yielded 14 studies. No differences were observed in growth or morbidity with early lipid initiation. We found a weak favorable association of non-purely soybean-based emulsions with the incidence of sepsis (RR: 0.75; 95% CI: 0.56, 1.00). CONCLUSIONS: The initiation of lipids within the first 2 d of life in VLBW infants appears to be safe and well tolerated; however, beneficial effects on growth could not be shown for this treatment nor for the type of lipid emulsion. Emulsions that are not purely soybean oil-based might be associated with a lower incidence of sepsis. Large-scale randomized controlled trials in preterm infants are warranted to determine whether early initiation of lipids and lipid emulsions that are not purely soybean oil-based results in improved long-term outcomes.

Nutritional support for extremely low-birth weight infants: abandoning catabolism in the neonatal intensive care unit.

PURPOSE OF REVIEW: Obviously, the ultimate goal in neonatology is to achieve a functional outcome in premature infants that is comparable to healthy term-born infants. As nutrition is one of the key factors for normal cell growth, providing the right amount and quality of nutrients could prove pivotal for normal development. However, many premature infants are catabolic during the first week of life, which has directly been linked to growth failure, disease, and suboptimal long-term outcome. This review describes the progress in research on parenteral nutrition for premature infants with a focus on amino acids and the influence of nutrition on later outcome. RECENT FINDINGS: Although randomized clinical trials on early nutrition for premature infants remain relatively sparse, evidence is accumulating on its beneficial effects both on the short-term and long-term. However, some research also warns for adverse effects. SUMMARY: Despite the fact that substantially improved nutritional therapies for preterm neonates have been implemented, still, some reluctance exists when it comes to providing high amounts of nutrition to the most immature infants. Pros and cons are outlined, as well as deficits in knowledge, when it comes to providing the optimal nutrient strategy in the first postnatal phase.

Initial nutritional management of the preterm infant.

Postnatal nutrition has a large impact on long-term outcome of preterm infants. Evidence is accumulating showing even a relationship between nutrient supply in the first week of life and later cognitive development in extremely low birth weight infants. Since enteral nutrition is often not tolerated following birth, parenteral nutrition is necessary. Yet, optimal parenteral intakes of both energy and amino acids are not well established. Subsequently, many preterm infants fail to grow well, with long-term consequences. Early and high dose amino acid administration has been shown to be effective and safe in very low birth weight infants, but the effect of additional lipid administration needs to be defined.

Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life.

BACKGROUND: We recently showed that parenteral administration of amino acids to premature infants immediately after birth is safe and results in a positive nitrogen balance and increased whole-body protein synthesis. However, we did not determine organ-specific effects; albumin, produced by the liver, is an important protein, but its concentration is often low in premature neonates during the first few days after birth. OBJECTIVE: The objective of the study was to test the hypothesis that the fractional and absolute albumin synthesis rates would increase with the administration of amino acids after birth, even at low nonprotein energy intake. DESIGN: Premature infants (<1500 g birth weight), who were on ventilation, received from birth onward either glucose only (control group, n = 7) or glucose and 2.4 g amino acid kg(-1) d(-1) (intervention group, n = 8). On postnatal day 2, all infants received a primed continuous infusion of [1-(13)C]leucine, and mass spectrometry techniques were used to determine the incorporation of the leucine into albumin. Results are expressed as medians and 25th and 75th percentiles. RESULTS: Albumin fractional synthesis rates in the intervention group were significantly higher than those in the control group [22.9% (17.6-28.0%)/d and 12.6% (11.0-19.4%)/d, respectively; P = 0.029]. Likewise, the albumin absolute synthesis rates in the intervention group were significantly higher than those in the control group [228 (187-289) mg kg(-1) d(-1) and 168 (118-203) mg kg(-1) d(-1), respectively; P = 0.030]. CONCLUSION: Amino acid administration increases albumin synthesis rates in premature neonates even at a low energy intake.

Amino acid administration to premature infants directly after birth.

OBJECTIVES: To test the hypothesis that the administration of 2.4 g amino acids (AA)/(kg.d) to very low birth weight infants is safe and results in a positive nitrogen balance. STUDY DESIGN: We conducted a randomized, clinical trial. Preterm infants with birth weights <1500 g received either glucose and 2.4 g AA/(kg.d) from birth onward (n=66) or solely glucose during the first day with a stepwise increase in AA intake to 2.4 g AA/(kg.d) on day 3 (n=69). Blood gas analysis was performed daily during the first 6 postnatal days; blood urea nitrogen levels were determined on days 2, 4, and 6; AA plasma concentrations and nitrogen balances were determined on days 2 and 4. Student t tests, Mann-Whitney tests, and chi2 tests were performed to compare groups. RESULTS: Infants supplemented with AA had no major adverse side effects. Their blood urea nitrogen levels were higher, nitrogen balance turned positive upon AA administration, and more AA concentrations were within reference ranges. CONCLUSIONS: High-dose AA administration to very low birth weight infants can be introduced safely from birth onward and results in an anabolic state.