Hester Vlaardingerbroek

Amino Acids and Proteins

Amino acids and protein are key factors for growth. The neonatal period requires the highest intake in life to meet the demands. Those demands include amino acids for growth, but proteins and amino acids also function as signalling molecules and function as neurotransmitters. Often the nutritional requirements are not met, resulting in a postnatal growth restriction. However, current knowledge on adequate levels of both amino acid as well as protein intake can avoid under nutrition in the direct postnatal phase, avoid the need for subsequent catch-up growth and improve later outcome.

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.

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fish oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fish oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7α-hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OSTα) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both OV and SL emulsions. Due to the presence of phytosterols in the SL emulsion, the differences in cholestasis and liver injury among lipid emulsion groups in vivo were weakly correlated with plasma and hepatic phytosterol content.

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.

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

Purpose of reviewObviously, 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 findingsAlthough 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. SummaryDespite 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.

Intravenous Lipids in Preterm Infants: Impact on Laboratory and Clinical Outcomes and Long-Term Consequences

Postnatal growth failure is still one of the most commonly observed morbidities in preterm infants. Intolerance of enteral nutrition is a common problem in these infants and in neonates with surgical conditions. Therefore, adequate parenteral nutrition is crucial to support organ development, including that of the brain. Short-term studies on the early introduction of parenteral lipids have demonstrated that early lipid administration seems safe and well tolerated and prevents essential fatty acid deficiency. Further well-designed and adequately powered studies are necessary to determine the optimal dose of lipid infusion and the long-term effects on morbidity, growth, and neurodevelopment. Administration of a pure soybean oil emulsion might result in excess formation of proinflammatory eicosanoids and peroxidation, and their use reduces the availability of the long-chain polyunsaturated fatty acids necessary for central nervous system development and immune function. Alternatives to the use of pure soybean oils include emulsions with partial replacement of soybean oil with medium-chain triglycerides, olive oil, and/or fish oil. These newer lipid emulsions offer many theoretical advantages. Future large-scale randomized controlled trials in premature infants should demonstrate whether these newer lipid emulsions are truly safe and result in improved short- and long-term outcomes. It seems safe to start lipid emulsions from birth onward at a rate of 2 g lipids/kg/day (based on short-term results only). Mixed lipid emulsions, including those containing fish oil, seem to reduce nosocomial infections in preterm infants and might reduce bile acid accumulation. Liver damage may be reduced by decreasing or removing lipids from parenteral nutrition or may be reduced by using fish oil-containing lipid emulsions containing high levels of vitamin E.

Commentary on "Fish Oil-Containing Lipid Emulsions in Adult Parenteral Nutrition: A Review of the Evidence" (https://doi.org/10.1177/0148607117721907)

BACKGROUND There is evidence from laboratory and animal studies that fish oil-containing intravenous lipid emulsions (FOC-IVLEs) have a beneficial effect on inflammation and the immune response, suggesting a possible clinical benefit. Clinical studies of FOC-IVLEs have reported mixed results. The aim of this review is to present findings from recent randomized controlled clinical trials and other quality clinical studies investigating the effects of administering intravenous fish oil alone or as part of a multilipid emulsion and to examine the quality of these studies in an objective, evidence-based manner. METHODS Studies comparing FOC-IVLEs with other IVLEs in adults were included. Thirty-four clinical studies were evaluated: 19 investigated levels of inflammatory and immune markers as an endpoint; 13 investigated rates of infection or sepsis; 3 investigated clinical outcomes in septic patients; and 29 investigated general clinical outcomes. RESULTS There was conflicting evidence for a beneficial effect of fish oil on levels of inflammatory and immune markers and some evidence that fish oil decreased the rate of postoperative atrial fibrillation. Studies generally reported few statistical differences in clinical outcomes and rates of infection and sepsis with FOC-IVLEs as compared with other IVLEs. The quality of reporting was generally poor, and the presented evidence for comparisons between FOC-IVLEs and other IVLEs was inconclusive or weak. CONCLUSIONS There is very little high-quality evidence that FOC-IVLEs have a more beneficial effect than other IVLEs on clinical outcomes in adult patients.

Multi-Omic Profiles of Hepatic Metabolism in TPN-fed Preterm Pigs Administered New Generation Lipid Emulsions

We aimed to characterize the lipidomic, metabolomic, and transcriptomic profiles in preterm piglets administered enteral (ENT) formula or three parenteral lipid emulsions [parenteral nutrition (PN)], Intralipid (IL), Omegaven (OV), or SMOFlipid (SL), for 14 days. Piglets in all parenteral lipid groups showed differential organ growth versus ENT piglets; whole body growth rate was lowest in IL piglets, yet there were no differences in either energy expenditure or 13C-palmitate oxidation. Plasma homeostatic model assessment of insulin resistance demonstrated insulin resistance in IL, but not OV or SL, compared with ENT. The fatty acid and acyl-CoA content of the liver, muscle, brain, and plasma fatty acids reflected the composition of the dietary lipids administered. Free carnitine and acylcarnitine (ACT) levels were markedly reduced in the PN groups compared with ENT piglets. Genes associated with oxidative stress and inflammation were increased, whereas those associated with alternative pathways of fatty acid oxidation were decreased in all PN groups. Our results show that new generation lipid emulsions directly enrich tissue fatty acids, especially in the brain, and lead to improved growth and insulin sensitivity compared with a soybean lipid emulsion. In all total PN groups, carnitine levels are limiting to the formation of ACTs and gene expression reflects the stress of excess lipid on liver function.

385 A Double Blind, Randomized Controlled Trial on the Resuscitation of Preterm Infants with 30% Versus 65% Oxygen at Birth

Background Resuscitation of term infants at birth with 100% oxygen increases oxidative stress with concomitant deleterious effects. Optimal levels for preterm infants are unknown. We hypothesized that resuscitation of preterms with initial FiO2 of 30% is safe, decreases oxidative stress and improves outcome compared to an initial FiO2 of 65%. Design Preterm infants (GA<32 weeks) were randomized to start resuscitation after birth with 30% or 65% oxygen. FiO2 was adjusted based on oxygen saturation and heart rate. Primary outcome was survival without bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Oxidative stress was determined by urinary DNA and protein oxidation markers, and plasma non protein bound iron. Results We included 194 infants, mean GA (284/7±21/7 weeks) and birth weight (1076±347 gram) were not different between groups. FiO2 was significantly different during the first 5 minutes following birth. Clinical outcomes (table) and oxidative stress markers were not statistically different between groups. Abstract 385 Table 1 Clinical outcome FiO2 30% (n=99) 65% (n=95) Mortality (%) 6.1 10.5 BPD (%) 23 15 Survival without BPD (%) 72 75 Intraventricular hemorrhage ≥stage 2 (%) 8.1 10.5 Retinopathy of prematurity ≥stage 2 (%) 6.1 5.3 Necrotizing enterocolitis ≥stage 2 (%) 4.0 3.2 Conclusion Resuscitation of preterm infants at birth with 30% oxygen is as safe as resuscitation with 65%, but does not offer benefits with regard to survival without BPD.