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This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

In den letzten Jahren brachten verschiedene Hersteller Milchgetranke fur Kleinkinder unter Bezeichnungen wie Kindermilch, Kleinkindmilch, Juniormilch oder im englischen Sprachraum „milk for kids“, „growing-up milk“ (GUM) oder „toddler milk“ auf den Markt, die aufgrund ihrer Zusammensetzung als vorteilhaft gegenuber Kuhmilch beworben werden. Die Ernahrungskommission der Deutschen Gesellschaft fur Kinder- und Jugendmedizin (DGKJ) stellt, wie bereits im Jahr 2001, fest, dass spezielle Milchgetranke einschlieslich Folgemilch fur die Ernahrung von Kleinkindern grundsatzlich nicht notwendig sind. Wenn jedoch Trinkmilch durch Kleinkindermilch ersetzt wird, sollten sich die Produkte in Bezug auf Kalzium-, Vitamin-A- und -B2-Gehalt an Vollmilch und in Bezug auf den Energiegehalt an teilentrahmter Kuhmilch orientieren. Wunschenswert ist, dass sie sich in Bezug auf den Jod- und Vitamin-D-Gehalt an den Vorgaben der Folgenahrung orientieren. Aromastoffe und Susungsmittel sollten moglichst vermieden werden. Die Produkte sollen aus Tasse oder Becher und nicht aus einer Saugflasche getrunken werden.

Background: We studied the impact of lifestyle, body composition, different insulin sensitivity indices and the first insulin response in healthy pre- and post-menopausal women with a low cardiovascular risk profile (the EU-RISC study, ‘Relationship between Insulin Sensitivity and Cardiovascular Disease’ ( n = 51, 47 ± 4 years, body mass index 23.6 ± 3.7 kg/m2, waist girth 79.2 ± 10.3 cm) on endothelial function (flow mediated arterial dilatation (FMD)), an early marker for atherosclerosis. Results: Waist circumference ( p = 0.06), tobacco consumption ( p = 0.02) and leucocyte count ( p = 0.09) were inversely related with FMD in both pre- and post-menopausal women. Neither insulin sensitivity nor first insulin response indices were correlated with FMD. In pre-menopausal women ( n = 24), waist ( p < 0.02), waist-to-hip ratio ( p < 0.02), HDL cholesterol ( p < 0.01) and smoking habits ( p < 0.03) were significantly correlated with endothelial function. In postmenopausal women ( n = 27) age ( r = −0.17, p = 0.04) was related with FMD. Conclusion: Smoking and waist circumference, a simple marker of visceral adiposity, were related with endothelial function in healthy pre- and post-menopausal women.

Background Accurate measurement of 17-hydroxyprogesterone (17-OHP) concentrations is essential for the correct diagnosis and treatment management of children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21 OHD). Methods We analysed 102 serum samples from 15 children with known 21 OHD twice using two different 17-OHP assays. 17-OHP concentrations were measured by an in-house radioimmunoassay (RIA) after recovery-corrected extraction and chromatographic purification and by a commercially available RIA without extraction (Immunotech). Results The correlation coefficient for results of pairs of 17-OHP concentrations was 0.974. The median ratio (17-OHP concentration measured with the commercial assay/17-OHP concentration measured with the in-house assay) was 0.593 with a 95% confidence interval ranging from 0.258 to 1.370. The ratio was constant throughout the average 17-OHP concentrations ranging from 0.24 to 149.2 nmol/L, as well as throughout the age range from 0.3 to 16.4 years. Conclusions Despite good overall correlation, absolute 17-OHP concentrations differed dramatically. This could lead to misclassification of patients suspected for 21 OHD on the basis of the hormonal profile and to a reduced quality during treatment monitoring of patients with 21 OHD with the risk of under- and overtreatment.

The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). We identified a homozygous mutation--c.215G--A (p.Gly72Glu)--in the alternatively spliced exon 3A of this enzyme in two siblings with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia who died within the 1st year of life. Functional investigation of intact mitochondria showed a deficiency of ATP synthesis in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts. The enzyme defect was confirmed by complementation analysis in yeast. This is the first report of patients with mitochondrial phosphate-carrier deficiency.

In patients with propionic aciduria, the accumulating metabolite propionyl-CoA causes a disturbance of the urea cycle via the inhibition of N-acetylglutamate synthesis. Lack of this allosteric activator results in an inhibition of carbamoylphosphate synthase (CPS). This finally leads to hyperammonaemia. In two patients with decompensated propionic aciduria the CPS activator carbamylglutamate was tested for its ability to antagonize the propionyl-CoA associated hyperammonaemia. Oral carbamyl glutamate administration resulted in a significant increase in ammonia detoxification and could avoid further dialysis therapy. Safe, fast and easy to administer, carbamyl glutamate improves the acute therapy of decompensated propionic aciduria by increasing ammonia detoxification and avoiding hyperammonaemia.

Beim Versuch, die Inhaltsstoffe von Sauglingsmilchnahrungen jenen der Muttermilch anzupassen, ist eine Fulle von Einzelsubstanzen in den Bereichen von Aminosauren, Fettsauren, Polyaminen, Nukleotiden, Oligosacchariden, Funktionsproteinen, Hormonen, Vitaminen und Mineralien zu beachten, denen in besonderen Situationen eine Bedeutung zugewiesen werden kann. Es werden gedankliche Ansatze fur an definierte Problemsituationen angepasste "Supplementierungspakete" fur Formulamilchnahrungen entwickelt.

L-asparaginase is frequently used in combination therapy for the treatment of lymphoid malignancies. We report 5 children aged between 8 and 14 years with neurologic complications presenting with headache and seizures during the first three weeks of L-asparaginase treatment. Three patients had venous thrombosis, one presented a parenchymal hemorrhage, and one showed a peculiar encephalopathy with extended cortical and subcortical lesions suggesting a neurotoxic reaction. Decreased fibrinogen and antithrombin III levels were found. Early MRI is critical even in cases with mild neurologic symptoms. Diagnosis should be followed by early cessation of l-asparaginase application.

Ataxia telangiectasia (AT) is a pleiotropic genetic disorder characterized by progressive neurodegeneration, especially of cerebellar Purkinje cells, immunodeficiency, increased incidence of cancer, and premature aging. The disease is caused by functional inactivation of the ATM (AT-mutated) gene product, which is thought to act as a sensor of reactive oxygen species and oxidative damage of cellular macromolecules and DNA. The compound phenotype of AT might thus be linked to a continuous state of oxidative stress leading to an increase of programmed cell death (apoptosis). To assess this hypothesis, we analyzed lipid peroxidation products and the oxidative stress associated DNA base damage 8-hydroxy-2-deoxyguanosine in patients with AT. Oxidative damage to lipids and DNA was found to be markedly increased in AT patients. These results indicate that ATM might play an important role in the maintenance of cell homeostasis in response to oxidative damage. In this context, a better control of levels of reactive oxygen species could be a rational foundation of therapeutic intervention to help alleviate some of the symptoms associated with AT.

Objectives: Our purpose was to characterize the decisive pathophysiologic factors that lead to renal stone formation (nephrolithiasis) in patients with cystic fibrosis (CF). Methods: Patients with CF (n = 96) were investigated with respect to lithogenic and inhibitory factors of urolithiasis and compared with 30 healthy control patients. They were subdivided into 2 groups, 86 without renal stones and 10 with renal stones. Results: All stones were exclusively composed of calcium oxalate. As a major pathogenic factor, a urinary disequilibrium between promoting and inhibitory components of stone formation, characterized mainly by hypercalciuria, hyperoxaluria, and hypocitraturia, was found in the patients with nephrolithiasis. They tended to have lower plasma phosphate concentrations and an increased urinary phosphate excretion. The citrate/calcium ratio proved to be a valuable means to discriminate patients with renal stones from control patients. Patients with stones had ingested more cotrimoxazole and ceftazidim, cumulatively, than patients without stones. There was an inverse correlation between the amounts of antibiotics ingested and the percentage of tubular phosphate reabsorption ( r = –0.91, P Conclusion: Renal stone formation in patients with CF is caused by a disequilibrium between promoting and inhibitory components of stone formation, which is dominated by hypercalciuria, hyperoxaluria, and hypocitraturia. Treatment with cotrimoxazole and ceftazidim, primarily, may lead to renal proximal tubular damage with an ensuing sequence of phosphate loss, increase of parathyroid hormone secretion, increased 1,25-dihydroxyvitamin D3 formation, and absorptive hypercalciuria. (J Pediatr 2002;140:103-9)

Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells Background High-output levels of nitric oxide (NO) are produced by rat mesangial cells (MCs) in response to proinflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) by the inducible isoform of NO synthase (iNOS). We tested modulatory effects of NO on the expression and activities of matrix metalloproteinases-9 and -2 (MMP-9 and MMP-2), respectively. Temporal and spatial expression of these MMPs and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), seems to be critical in the extensive extracellular matrix (ECM) remodeling that accompanies sclerotic processes of the mesangium. Methods and Results. Using the NO donors S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) and DETA-NONOate, we found strong inhibitory effects of NO mainly on the IL-1β–induced MMP-9 mRNA levels. NO on its own had only weak effects on the expression of MMP-9 and MMP-2. The addition of the NOS inhibitor N G -monomethyl L-arginine (L-NMMA) dose dependently increased steady-state mRNA levels of cytokine-induced MMP-9, suggesting that endogenously produced NO exerts tonic inhibition of MMP-9 expression. MMP-9 activity in conditioned media from MCs costimulated with IL-1β and NO donor contained less gelatinolytic activity than media of cells treated with IL-1β alone. Exogenously added NO did not alter gelatinolytic activity of MMP-9 in cell-free zymographs. The expression levels of TIMP-1 were affected by NO similarly to the expression of MMP-9. Conclusion We conclude that NO modulates cytokine-mediated expression of MMP-9 and TIMP-1 in rat MCs in culture. Our results provide evidence that NO-mediated attenuation of MMP-9 gelatinolytic activity is primarily due to a reduced expression of MMP-9 mRNA, and not the result of direct inhibition of enzymatic activity.

Maple syrup urine disease is an autosomal recessive inherited disorder of branched-chain amino acid metabolism due to deficiency of the branched-chain alpha-keto acid dehydrogenase complex. The disease was originally named after the characteristic sweet aroma, reminiscent of maple syrup, present in the body fluids of affected patients. Until now, the substance responsible for the odour has not been positively identified. Using enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS), we could demonstrate that 4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone), a well-known flavour impact compound present in fenugreek and lovage, was present in urine from seven patients with maple syrup urine disease. Urine samples from healthy control persons lacked sotolone. We have shown that sotolone is responsible for the characteristic odour of maple syrup urine disease and, since maple syrup also contains sotolone, the naming of this disease appears to be correct.

We report the case of an 11-year-old girl presenting with a 1.5-year history of swan neck-like deformed joint contractures of both hands. A possible diagnosis was sought in a wide range of rheumatological, metabolic, and neurological disorders. After detailed diagnostic procedures to exclude an organic pathology, steps were taken to establish a psychogenic origin. She showed symptoms that were incongruent with an organic neurological disorder, for example, a paroxysmal fluctuating course, reaction to placebo, and complete remission with psychotherapy and physiotherapy. The psychosomatic evaluation revealed a highly emotional conflict. This bizarre case demonstrates that secondary contractures are by no means an exclusion criterion for a psychogenic dystonia.

Nahrstoffanteile sowie auch nahrstoffunabhangige trophische Faktoren beeinflussen sowohl die Proliferation als auch die Differenzierung unterschiedlicher Zellbestandteile der Darmwand. Die resorptive Mukosa mus dabei gedanklich von immunologisch wirksamen Zellen des Darm-assoziierten lymphatischen Gewebes (GALT) unterschieden werden. Glutamin ist das oxidative Hauptenergiesubstrat von Enterozyten und ein wesentlicher Lieferant von Synthesestickstoff. Diese Bedeutung von Glutamin wird v.a. bei Schwerkranken deutlich. Die Aminosauren Arginin und Ornithin haben v.a. als Ausgangssubstanzen der NO- und der Polyaminsynthese Bedeutung fur die Eutrophie immunkompetenter Darmzellen. Fermentable Kohlenhydrate werden in den unteren Darmabschnitten bakteriell zu hauptsachlich den kurzkettigen Fettsauren Azetat, Propionat und Butyrat vergoren. Diese uben u.a. uber eine Verbesserung des Blutflusses eine trophische Wirkung auf die Kolonschleimhaut aus. Unter den nahrungsunabhangigen Substanzen sind es v.a. die Hormone Gastrin und Enteroglukagon sowie auch unterschiedliche Wachstumsfaktoren, die zum Erhalt einer eutrophen Schleimhaut beitragen.

Newborns (n = 84) from families with a positive history for atopic dermatitis were pro-spectively investigated. 71 children were exclusively breast fed (group A), whereas 13 (group B) received a partial whey protein hydrolysate (Beba HA; Nestle AG) for up to maximally the first six weeks of life and were also exclusively breast fed thereafter. All mothers were instructed to use only food stuffs of low allergen content. After 12 months, 12 children (17 %) in group A had developed atopic dematitis whereas none in group B showed any atopic signs. After 18 months 23% of the children in group A showed manifestations of atopic dermatitis. In group B still no child showed disease symptoms. These results support the idea of tolerance by ingestion of 2 to 10 kD proteins during the early weeks of life.

The composition of infant milk formula intends to mirror breast milk as close as possible. However, there are a variety of substances, like amino acids, fatty acids, polyamines, nucleotides, oligosaccharides, functional proteins, hormones, vitamins, and minerals, which are attributed effects in special situations. A concept is proposed to develop problem oriented "supplementation packages" for infant milk formula.

Patienten: Wir berichten uber Therapie und Verlauf bei 4 Patienten mit nonketotischer Hyperglyzinamie, 3 Madchen mit neonataler und 1 Junge mit infantiler Form. Trotz fruher Diagnosestellung und Mehrfachtherapie inklusive Dextromethorphan und Na-Benzoat kam es bei 2 Madchen mit neonataler Form zu einem therapierefraktaren Verlauf und zum Exitus im Alter von 16 bzw. 50 Monaten, die 3. Patientin uberlebte mit schwerster psychomotorischer Retardierung, Opisthotonus, Tetraspastik und Anfallsleiden. Na-Benzoat fuhrte zwar zu einer Absenkung der Glyzinkonzentration (bei stets pathologischer Liquor-Serum-Glyzin-Ratio), konnte den deletaren Verlauf jedoch nicht beeinflussen. Der Patient mit der infantilen Form ist schwer psychomotorisch retardiert, zeigt aber unter Dextromethorphan seit nunmehr uber 3 Jahren stete Entwicklungsfortschritte und Anfallsfreiheit. Diskussion: Bei der neonatalen nonketotischen Hyperglyzinamie kann derzeit nur eine symptomatische Therapie inklusive eines Grand-mal-Schutzes empfohlen werden, da die Hirnlasion bereits intrauterin erworben und keine effektive Therapie bekannt ist, bei der infantilen Form ist ein Therapieansatz mit Dextromethorphan gerechtfertigt. Eine Pranataldiagnose in „Risikofamilien” ist unverzichtbar.

The effect of daily human growth hormone (hGH) injections (3 I.U./m2/day) on tissue anabolism was determined in six patients with Ullrich-Turner syndrome (XO) (8.7-19 years of age) using novel techniques such as whole body leucine kinetics during continuous infusion of L-(Methyl-2H3)-leucine and urinary pseudouridine (5-ribosyluracil) excretion on the one hand and traditional methods like serum urea and amino acid concentrations on the other. Pseudouridine is only found in ribonucleic acid (RNA) and is neither reincorporated nor catabolically broken down and is therefore considered an ideal index of whole body RNA turnover. The mean L-(Methyl-2H3)-leucine turnover of the six XO patients before hGH was 1.90 +/- 0.15 mumoles/kg per minute. After 3 months of hGH-treatment it had increased in three patients, whereas it had decreased in the other three. The results obtained with the stable isotope technique were correlated with the urinary pseudouridine concentrations (r = 0.68; P0.01). The growth rates were positively correlated with leucine turnover (r = 0.63; P0.02) and urinary pseudouridine concentration (r = 0.73; P0.006) as well as negatively correlated with the serum urea concentrations r = -0.62; P0.03). The decrease in the individual serum urea concentrations were tightly correlated with the hGH induced change in growth rate (r = -0.90; P0.01). The individual bone ages were negatively correlated with the hGH induced changes in leucine turnover (r = -0.77; P0.003) as well as with the urinary pseudouridine concentrations (r = -0.87; P0.0002). The hGH effect on leucine and RNA turnover, showing effectiveness only until a developmental age between 11 and 12 years, leads the discussion of the ideal moment of oestrogen supplementation when girls with Ullrich-Turner syndrome are treated with hGH in early adolescence.The protein metabolism of patients with Ullrich-Turner syndrome is influenced by hGH in an age dependent manner. In a clinical setting, pseudouridine, an easily determined derivative of ribonucleic acids, may be able to replace the tedious work with expensive stable isotopes when questions related to tissue anabolism are to be answered.

The effects of sodium citrate supplementation to improve aspartic acid supply in a 5-year-old girl with argininosuccinate lyase deficiency were studied over a period of 5 years under constant and total parenteral nutrition. Daily increasing doses of sodium citrate (0-8 mmol/kg) were continuously infused i.v.. Her standard therapy with arginine hydrochloride (4 mmol/kg/day) and sodium benzoate (200 mg/kg/day) was continued. Serum citrulline concentrations were reduced by citrate supplementation (161.8-41.7 mumol/l). Correspondingly serum concentrations of argininosuccinate and its anhydrides rose (270-458 mumol/l), positively correlated with the doses of sodium citrate. Renal elimination of argininosuccinate did not change measurably. There was no improvement in plasma ammonia concentration, which remained between 88 and 136 mumol/l. A long-standing hepatomegaly did not improve. The patient developed a significant alkalosis with blood pH-values increasing up to 7.55. The alkalosis lead to a reduction in renal ammonium elimination by at least 5.3 mmol/kg per day; the portion of ammonium-nitrogen decreased from 54.2% to finally 9% of total urinary nitrogen. Nevertheless total urinary nitrogen elimination, as measured by pyrochemiluminescence, improved by 24.5% during the 5 days and rose from 2065 mg nitrogen/day to 2570 mg/day. This improvement could not be explained by the metabolites determined and corresponded with an increase in chemically undefined nitrogen excretion, which rose from 0% to 65.9% of total urinary nitrogen. Further investigations are necessary to elucidate the nature of these unexplained nitrogen-containing compounds. CONCLUSION. Sodium citrate supplementation improved renal nitrogen elimination in a patient with argininosuccinate lyase deficiency in the observation period of 5 days by up to 24.5%.

The purpose of our study was to evaluate the influence of serum carnitine levels on the metabolic status and lipid profile of patients on continuous ambulatory peritoneal dialysis (CAPD).We studied the lipid profile, the metabolic status (triceps, skinfold thickness, midarm muscle circumference, relative body weight, serum total protein, albumin), and serum carnitine levels in 22 patients (11 male, 11 female) on CAPD.The results are summarized as follows: mean serum total camitine (TC) was normal, free carnitine (FC) was reduced, while acylcarnitine (AC) was elevated in our patients (pNo correlation was found between carnitine and midarm muscle circumference, triceps skinfold thickness, albumin, total cholesterol, and HDL. or LDL-cholesterol.Further studies are needed to confirm our results.

Summary Background: Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids (LCPUFA) has been related to visual and cognitive development in healthy children in several studies. Children with phenylketonuria (PKU) consume diets with very low contents of preformed LCPUFA. We studied prospectively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life. Subjects and methods: Infants with PKU were enrolled at diagnosis (

Congenital disorders of glycosylation are a group of inherited metabolic multisystem disorders characterized by defects in the glycosylation of proteins and lipids. In most cases, neuromuscular disease is present. The purpose of this study was to characterize the cardiological aspects in this disorder.From the literature, we identified six children with congenital disorders of glycosylation associated with cardiac disease. We then screened for cardiovascular manifestations 20 patients diagnosed with congenital disorders of glycosylation at our own institution.Of the 6 patients identified in the literature, 4 had hypertrophic cardiomyopathy, while in the other 2 the cardiac diagnosis was unclear. The mean age at cardiac diagnosis was 5 months, with a range from 34 weeks to 24 months. Of the patients, five had died at a mean age of 3.5 months, with a range from 1.5 to 6 months, with one documented cardiac death. Three of our 20 patients (15%) had coexistent cardiomyopathy, and in three additional patients presenting with cardiomyopathy we made the diagnosis of a congenital disorder of glycosylation. In our cohort, dilated cardiomyopathy was found in two-thirds of the patients, with hypertrophic cardiomyopathy in the other third. The mean age at cardiac diagnosis was 19 months, with a range from 0.5 to 84 months. Of these patients, two died in infancy at a mean age of 4 months, specifically at 1.5 and 7 months, due to cardiac disease, with one dying suddenly. The remaining four patients are alive with minor to severe cardiac dysfunction.We conclude that congenital disorders of glycosylation have to be considered in the differential diagnosis of children presenting with cardiomyopathy, and that all patients with congenital disorders of glycosylation should be screened for an associated cardiomyopathy. Cardiac involvement contributes significantly to morbidity and mortality, and probably to sudden cardiac death in this disorder.

To evaluate in premature infants a new parenteral lipid emulsion based on olive and soybean oils (ratio 4:1), with less polyunsaturated fatty acids (PUFA) and more alpha-tocopherol than standard soybean oil emulsion.Premature infants (gestational age, 28-37 weeks) were randomized to receive one of the two emulsions within the first 72 hours of life. The triglyceride dose was increased to 2 g/kg/day within 3 days. Plasma phospholipid fatty acids, alpha-tocopherol/lipid ratio, and urinary malondialdehyde (MDA) excretion were determined at baseline and after 7 days.Of 45 recruited infants, 33 completed the study per protocol (15 soybean oil, 18 olive oil emulsion). At study end, groups did not differ in plasma phospholipid arachidonic acid, total n-6 and n-3 metabolites, but the olive oil group showed higher values of the PUFA intermediates C18:3n-6 (0.19% +/- 0.01% vs. 0.13% +/- 0.02%, P0.05) and C20:3n-6 (2.92% +/- 0.12% vs. 2.21% +/- 0.17%, P = 0.005). The plasma alpha-tocopherol/total lipd ratio was higher in the olive oil group (2.45 +/- 0.27 micromol/mmol vs. 1.90 +/- 0.08 micromol/mmol, P = 0.001), whereas urinary MDA excretion did not differ.The lower PUFA supply with the olive/soybean oil emulsion appears to enhance linoleic acid conversion. The reduced PUFA content, combined with a higher antioxidant intake in the olive oil group, results in an improved vitamin E status. The olive oil-based emulsion is a valuable alternative for parenteral feeding of preterm infants who are often exposed to oxidative stress, while their antioxidative defense is weak.

The chiral metabolite 2-hydroxysebacic acid (2-HS) is considered to be an important diagnostic marker for peroxisomal disorders. The pathway of formation of 2-HS, excreted in increased amounts in patients with peroxisomal diseases, is not absolutely clear. Moreover, there is no information about the enantiomeric distribution of 2-HS in human urine. Here, we describe the stereodifferentiation of 2-HS in urine samples of nine patients with Zellweger syndrome (ZS), and for the first time in urine samples of premature infants fed a medium-chain triglyceride (MCT)-containing diet. Using enantioselective multidimensional gas chromatography-mass spectrometry, an increased excretion of 2R-HS was observed in all investigated ZS patients. 2-HS was also present in urine samples of premature infants fed MCT. Analogously to the ZS patients, a dominant 2R-HS excretion in the urine samples of the premature infants was identified. The formation of 2-HS is expected to result from the same or similar pathways as described for ZS patients. Additionally, we determined the absolute configuration of urinary 3-hydroxysebacic acid (3-HS) in the cases investigated. The enantioselective analysis provides further information for the diagnosis and treatment of patients with impaired peroxisomal fatty acid oxidation. Further insight into the metabolic origin and the biochemical pathway leading to these urinary metabolites is provided.

Long-chain polyunsaturated fatty acids (LCP) are considered conditionally essential nutrients for the infant born prematurely, and attempts are being made to match fatty acid profiles of formula and breast fed infants. In this double-blind, randomized study we investigated the effects of a formula enriched with both n-6 and n-3 LCP on plasma fatty acid profiles, antioxidant status and growth of premature infants. 29 infants received either a formula devoid of LCP or a LCP supplemented formula (0.5 g/100 g fat linoleic acid metabolites, 0.8 g/100 g fat alpha-linolenic acid metabolites). 17 breast fed infants served as a control group. At study entry as well as two and four weeks later, plasma and urine samples were collected, growth data obtained and food tolerance was documented. At the end of the four week study period, plasma docosahexaenoic acid (DHA) levels of supplemented infants were significantly higher than those of unsupplemented infants and similar to those of infants fed human milk. Plasma n-6 LCP concentrations including arachidonic acid (AA) were similar between groups. The plasma alpha-tocopherol levels of breast fed and supplemented infants were similar and tended to be lower than in infants fed the formula devoid of LCP. Urinary malondialdehyde (MDA) excretion of formula fed infants was significantly higher compared to infants fed human milk, but did not differ between the two formula groups. Parameters of growth and milk tolerance did not differ between groups. Our results demonstrate that plasma LCP levels similar to those of breast fed infants can be achieved with the LCP supplemented formula used in this trial, without evidence of adverse effects of the LCP enrichment.