Akker, C.H.P. van den

Amino acid metabolism in the human fetus at term: Leucine, valine, and methionine kinetics (Article)

2011-12-01T00:00:00Z

Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.

Feeding very-low-birth-weight infants: Our aspirations versus the reality in practice (Article)

2011-06-01T00:00:00Z

Recently, new guidelines for enteral feedings in premature infants were issued by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition. Nevertheless, practice proves difficult to attain suggested intakes at all times, and occurrence of significant potential cumulative nutritional deficits 'lies in wait' in the neonatal intensive care unit. This review describes several aspects that are mandatory for optimizing nutritional intake in these vulnerable infants. These aspects range from optimal infrastructure to the initiation of parenteral nutrition with proper transition to enteral breast or formula feedings. Proper monitoring of nutritional tolerance includes serum biochemistry although proper specific markers are unknown and safety reference values are lacking. Although a lot of progress has been made through research during the last few decades, numerous questions still remain unanswered as to what would be the optimal quantity and quality of the various macronutrients. The inevitable suboptimal intake may, however, contribute significantly to the incidence of neonatal diseases, including impaired neurodevelopment. Therefore, it is pivotal that all hospital staff acknowledges that preterm birth is a nutritional emergency and that all must be done, both in clinical practice as well as in research, to reduce nutritional deficits. Copyright

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

2010-05-01T00:00:00Z

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.

Recent advances in our understanding of protein and amino acid metabolism in the human fetus (Article)

2010-01-01T00:00:00Z

PURPOSE OF REVIEW: Premature infants often suffer from suboptimal outcome, at least partially due to suboptimal nutrition. Gaining insight into human fetal amino acid metabolism might ultimately lead to an improved nutritional strategy for prematurely born infants. Our aim was, therefore, to discuss recent findings with regard to human fetal amino acid metabolism. RECENT FINDINGS: Human fetal protein and amino acid metabolism can be studied in vivo using stable isotope techniques. To date, however, only a few studies employing these techniques have been performed. For one, it was shown in vivo that essential amino acids are transported at different rates across the human placenta. In addition, tyrosine appears not to be a conditionally essential amino acid in the fetus at term, as phenylalanine is hydroxylated into tyrosine at considerable rates. Furthermore, albumin is synthesized at very high rates at two-thirds of gestation; higher than prematurely born infants do at a neonatal intensive care unit. This could indicate that postnatal nutrition of very immature infants can be improved. SUMMARY: Although technically challenging, more studies regarding human fetal amino acid metabolism should be performed. Premature infants could then benefit from this knowledge from new nutritional strategies.

Analysis of [U-13C6]glucose in human plasma using liquid chromatography/isotope ratio mass spectrometry compared with two other mass spectrometry techniques (Article)

2009-12-15T00:00:00Z

The use of stable isotope labelled glucose provides insight into glucose metabolism. The13C-isotopic enrichment of glucose is usually measured by gas chromatography/mass spectrometry (GC/MS) or gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). However, in both techniques the samples must be derivatized prior to analysis, which makes sample preparation more labour-intensive and increases the uncertainty of the measured isotopic composition. A novel method for the determination of isotopic enrichment of glucose in human plasma using liquid chromatography/ isotope ratio mass spectrometry (LC/IRMS) has been developed. Using this technique, for which hardly any sample preparation is needed, we showed that both the enrichment and the concentration could be measured with very high precision using only 20μL of plasma. In addition, a comparison with GC/MS and GC/IRMS showed that the best performance was achieved with the LC/IRMS method making it the method of choice for the measurement of13C-isotopic enrichment in plasma samples. Copyright

Initial nutritional management of the preterm infant (Article)

2009-11-01T00:00:00Z

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.

Human fetal amino acid metabolism at term gestation (Article)

2009-01-01T00:00:00Z

Background: Knowledge on human fetal amino acid (AA) metabolism, largely lacking thus far, is pivotal in improving nutritional strategies for prematurely born infants. Phenylalanine kinetics is of special interest as is debate as to whether neonates will adequately hydroxylate phenylalanine to the semiessential AA tyrosine. Objective: Our aim was to quantify human fetal phenylalanine and tyrosine metabolism. Design: Eight fasted, healthy, pregnant women undergoing elective cesarean delivery at term received primed continuous stable-isotope infusions of [1-13C]phenylalanine and [ring-D4]tyrosine starting before surgery. Umbilical blood flow was measured by ultrasound. Maternal and umbilical cord blood was collected and analyzed by gas chromatography-mass spectrometry for phenylalanine and tyrosine enrichments and concentrations. Data are expressed as medians (25th-75th percentile). Results: Women were in a catabolic state for which net fetal AA uptake was responsible for ≥25%. Maternal and fetal hydroxylation rates were 2.6 (2.2-2.9) and 7.5 (6.2-15.5) μmol phenylalanine/(kg·h), respectively. Fetal protein synthesis rates were higher than breakdown rates: 92 (84-116) and 73 (68-87) μmol phenylalanine/(kg·h), respectively, which indicated an anabolic state. The median metabolized fraction of available phenylalanine and tyrosine in the fetus was <20% for both AAs. Conclusions: At term gestation, fetuses still show considerable net AA uptake and AA accretion [converted to tissue ≈12 g/(kg·d)]. The low metabolic uptake (AA usage) implies a very large nutritional reserve capacity of nutrients delivered through the umbilical cord. Fetuses at term are quite capable of hydroxylating phenylalanine to tyrosine.

Fetal Food - Preemie's Prerequisite? Studies on human fetal and neonatal protein metabolism (Doctoral Thesis)

2008-12-11T00:00:00Z

In 1960, the terms ‘neonatology’ and ‘neonatologist’ were first coined in a textbook on newborns. In hindsight, that decade turned out to be the start of modern care for prematurely born babies. Since then, survival chances for premature infants improved dramatically: for 1-kg-weighing infants from hardly any to approximately 90% nowadays. In addition, due to ongoing research, many infants born too early now have good health outcome, although there is also a large group facing mild handicaps and a smaller group facing more severe handicaps. In the Netherlands, the incidence of all live births delivered preterm – that is before 37 weeks of gestation – was 7.3% in 2004. Infants born alive very preterm (<32 weeks) make up 1.1% of the 194.007 births in the Netherlands that same year. These very preterm infants spent on average 28 days on a neonatal intensive care unit (NICU). In the United States, the current incidence of births delivered preterm amounts 12.8% and is thus higher than in the Netherlands. Moreover, the percentage is on the rise: between 1981 and 2005 it increased with 35% (Figure 1). Although we are aware of several factors responsible for this increase (see below), prematurity is becoming a problem affecting society more and more.

Quality of amino acid solutions for preterm infants (Article)

2008-04-01T00:00:00Z

Parenteral amino acid and energy administration to premature infants in early life (Article)

2007-02-01T00:00:00Z

After birth, the nutritional supply through the umbilical cord ceases. Premature infants do not immediately tolerate full enteral feedings, yet they retain high nutritional needs for both growth and metabolic maintenance. Parenteral nutrition should therefore be initiated as quickly as possible after premature birth, thereby reducing the dependence on endogenous substrates. Intrauterine studies show very high amino acid uptake, clearly exceeding accretion rates. Studies covering the early neonatal period demonstrate that the initiation of high-dose amino acid administration directly after birth is safe and effective, even at low energy intakes. Future research should reveal whether usage could be improved through better amino acid solutions or by providing more energy via lipids from birth onwards as well.