[Show abstract][Hide abstract] ABSTRACT: SMOFlipid 20% is an intravenous lipid emulsion (ILE) containing soybean oil, medium-chain triglycerides, olive oil, and fish oil developed to provide energy, essential fatty acids (FAs), and long-chain ω-3 FAs as a mixed emulsion containing α-tocopherol. The aim was to assess the efficacy and safety of this new ILE in pediatric patients receiving home parenteral nutrition (HPN) compared with soybean oil emulsion (SOE).
This single-center, randomized, double-blind study included 28 children on HPN allocated to receive either SMOFlipid 20% (n = 15) or a standard SOE (Intralipid 20%, n = 13). ILE was administered 4 to 5 times per week (goal dose, 2.0 g/kg/d) within a parenteral nutrition regimen. Assessments, including safety and efficacy parameters, were performed on day 0 and after the last study infusion (day 29). Lipid peroxidation was determined by measurement of thiobarbituric acid reactive substances (TBARS).
There were no significant differences in laboratory safety parameters, including liver enzymes, between the groups on day 29. The mean ± standard deviation changes in the total bilirubin concentration between the initial and final values (day 29 to day 0) were significantly different between groups: SMOFlipid group -1.5 ± 2.4 µmol/L vs SOE group 2.3 ± 3.5 µmol/L, P < .01; 95% confidence interval [CI], -6.2 to -1.4). In plasma and red blood cell (RBC) phospholipids, the ω-3 FAs C20:5ω-3 (eicosapentaenoic acid) and + C22:6ω-3 (docosahexaenoic acid) increased significantly in the SMOFlipid group on day 29. The ω-3:ω-6 FA ratio was significantly elevated with SMOFlipid 20% compared with SOE group (plasma, day 29: 0.15 ± 0.06 vs 0.07 ± 0.02, P < .01, 95% CI, 0.04-0.11; and RBC, day 29: 0.23 ± 0.07 vs 0.14 ± 0.04, P < .01, 95% CI, 0.04-0.13). Plasma α-tocopherol concentration increased significantly more with SMOFlipid 20% (15.7 ± 15.9 vs 5.4 ± 15.2 µmol/L, P < .05; 95% CI, -2.1 to 22.6). The low-density lipoprotein-TBARS concentrations were not significantly different between both groups, indicating that lipid peroxidation did not differ between groups.
SMOFlipid 20%, which contains 15% fish oil, was safe and well tolerated, decreased plasma bilirubin, and increased ω-3 FA and α-tocopherol status without changing lipid peroxidation.
Journal of Parenteral and Enteral Nutrition 09/2010; 34(5):485-95. · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This prospective study aimed to establish the effect of recombinant human growth hormone (rhGH) on intestinal function in children with short bowel syndrome (SBS). Eight children with neonatal SBS were included. All were dependent on parenteral nutrition (PN) for >3 years (range, 3.8-11.6 years), with PN providing >50% of recommended dietary allowance for age (range, 50%-65%). The subjects received rhGH (Humatrope) 0.13 mg/kg/d subcutaneously over a 12-week period. The follow-up was continued over a 12-month period after rhGH discontinuation. Clinical and biological assessments were performed at baseline, at the end of the treatment period, and 12 months after the end of treatment. No side effects related to rhGH were observed. PN requirements were decreased in all children during the course of rhGH treatment. Between baseline and the end of treatment, significant increases were observed in concentrations (mean ± standard deviation) of serum insulin-like growth factor 1 (103.1 ± 49.9 µg/L vs 153.5 ± 82.2 µg/L; P < .01), serum insulin-like growth factor-binding protein 3 (1.7 ± 0.6 mg/L vs 2.5 ± 0.9 mg/L; P < .001), and plasma citrulline (16.5 ± 14.8 µmol/L vs 25.2 ± 18.3 µmol/L; P < .05). A median 54% increase in enteral intake (range, 10%-244%) was observed (P < .001) and net energy balance improved significantly (P < .002). It was necessary for 6 children to be maintained on PN or restarted after discontinuation of rhGH treatment, and they remained on PN until the end of the follow-up period. A 12-week high-dose rhGH treatment allowed patients to decrease PN, but only 2 patients could be definitively weaned from PN. Indications and cost-effectiveness of rhGH treatment for SBS pediatric patients need further evaluation.
Journal of Parenteral and Enteral Nutrition 09/2010; 34(5):513-20. · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To point new insights in the cholestasis that is a complication of both intestinal failure and parenteral nutrition. View on liver disease has recently evolved with the onset of fish oil-based intravenous lipid emulsions (ILE).
Focused on the role of ILE in causing liver disease. Reversal of cholestasis was recently achieved in infants with short bowel syndrome, by replacing the 'reference' soybean oil-based ILE by fish oil-based ILE.
It is likely that this reversal involves several factors such as the change in n-6: n-3 ratio, the reduction in phytosterol load, the increased provision of alpha-tocopherol as antioxidant agent. Alternative issue might be based on the use of a new generation of ILE aiming to provide n-3 and to reduce n-6 fatty acids load while enhancing alpha-tocopherol intake. New data are based on the use of an ILE containing a balanced proportion of four types of oil as a physical mixture of 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil with amounts of alpha-tocopherol calculated according to the number of double bonds. This new emulsion was reported to be beneficial in reversing or preventing liver disease.
Current opinion in organ transplantation 07/2009; 14(3):256-61. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The supplementation of vitamin K is necessary for total parenteral nutrition (TPN) patient to avoid hemorrhagic risk. In home TPN and to simplify the children administration, the vitamin K could be added once or twice monthly in admixtures. The aim of this work was to evaluate the vitamin K stability (20mg/L) in usual conditions of administration (binary or ternary mixtures, at room temperature and at artificial light for 24hours) and at storage (binary mixtures protected from light, at 4°C for 12hours). Each step of the study was performed with quantification using HPLC method coupled with UV detection at 244nm on five TPN bags. The results of this study show that the vitamin K was stable for 24hours at light exposure and at room temperature in binary mixture (96.6%) also ternary (99.8%). The vitamin K was stable at 4°C for 12 days (98.4%). This work shows that vitamin K can be added directly in TPN and could avoid painful intramuscular injection. Such nutritional admixtures could be prepared beforehand and allow administration at home. This practice is actually consensual in gastro-enterology department at Necker University Hospital. A clinical and biologic monitoring is essential.
Nutrition Clinique Et Metabolisme - NUTR CLIN METAB. 01/2009; 23(3):113-117.
[Show abstract][Hide abstract] ABSTRACT: More information is needed regarding the prognosis of children receiving home parenteral nutrition (HPN). This article describes 20-year outcome data in children receiving HPN and provides separate profiles for the major pediatric diagnostic subgroups.
This retrospective study included children who started receiving HPN between January 1, 1980, and December 31, 1999, in a single pediatric HPN center.
A total of 302 children were recruited, 230 (76%) with primary digestive disorders and 72 (24%) with nonprimary digestive disorders. Median age at HPN onset was 1.5 years. Median duration of HPN was 1.3 years. By January 1, 2000, 54% had weaned from HPN, 26% were still receiving HPN, 16% had died, and 4% had undergone intestinal transplantation. The survival probabilities at 2, 5, 10, and 15 years were 97%, 89%, 81%, and 72%, respectively. The likelihood and cause of death depended on the underlying diagnosis. Nine percent of children with primary digestive disorders died, 24% from their primary disease and 48% from liver disease or sepsis. Children with intractable diarrhea of infancy had the highest mortality rate (25%) and the highest incidence of liver disease (48%; P = 0.0002). Thirty-eight percent of children with primary nondigestive diseases died, 94% from their primary disease and 6% from liver disease or sepsis.
Outcome and survival of children receiving HPN are mainly determined by their underlying diagnosis. Nearly all children with primary digestive disease survive if referred early to an expert center.
Journal of pediatric gastroenterology and nutrition 04/2007; 44(3):347-53. · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A better knowledge of intestinal adaptation after resection is required to improve the nutritional support that is given to patients. The aim of this study was to understand the metabolic changes underlying early adaptation after massive intestinal resection.
Rats were assigned to either 80% intestinal resection or transection. All animals received the same intragastric nutrition. On day 8, plasma glutamine turnover was measured. Substrate use was determined on isolated enterocytes that were incubated in the presence of D-[U-(14)C] glucose (2 mmol/L), L-[U-(14)C] glutamine (2 mmol/L), L-[U-(14)C] arginine (1 mmol/L), or L-[1-(14)C] ornithine (1 mmol/L).
Plasma glutamine turnover was similar in both groups. The rate of enterocyte glutamine use was significantly increased in the resection group, although the maximal glutaminase activity was unchanged. Glutathione generation was enhanced 3-fold in remnant intestine as compared with transected intestine (P <.05). L-ornithine decarboxylation was increased markedly in resected animals (P <.05), without any detectable change of maximal ornithine decarboxylase activity.
The early phase of intestinal adaptation after resection induces changes in enterocyte glutamine and ornithine metabolism that may be related, in part, to increased de novo polyamine synthesis. This observation suggests that a supplementation of artificial nutrition by nutrients that lead to the generation of trophic agents may be of potential interest.
Surgery 06/2004; 135(6):649-56. · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intravenous administration of nutrition mixtures induces endothelial damage and arterial wall remodeling in animal models. To study endothelial function and common carotid artery mechanical properties in children receiving parenteral nutrition, we used noninvasive ultrasonic measurements in 18 children on parenteral nutrition and 18 controls. No difference appeared in the geometry of the common carotid artery (intima media thickness, systolic and diastolic diameters) between the patients on parenteral nutrition and the controls. The incremental elastic modulus was significantly higher in the patients on parenteral nutrition (1.8 +/- 0.4 versus 1.4 +/- 0.5 4 mm Hg x 10(3), p < 0.05) reflecting alteration of the elastic properties of the arterial wall independent of the vessel geometry. The flow-mediated dilatation of the brachial artery was significantly lower in the patients on parenteral nutrition (6 +/- 3 versus 8 +/- 3%, p < 0.05), whereas the dilatation after glyceryl trinitrate administration was similar (22 +/- 9 versus 25 +/- 9%). Children on parenteral nutrition exhibit endothelial dysfunction and altered stiffness of the common carotid artery. The noninvasive methods used in this study may prove useful for objectively determining the effects of various preventive methods.
Pediatric Research 06/2004; 55(5):789-93. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. – Metabolic bone disease (MBD) with a decrease in bone mineral density (BMD), osteoporosis, pain and fractures has been described in adults on long-term parenteral nutrition (LTPN), while a few data exists in children. The aim of the present study was to assess the prevalence and clinical features of MBD in children on LTPN.Patients and methods. –: All the children on LTPN (more than 6 months) who had undergone at least one dual energy X-ray absorptiometry (DEXA) before puberty onset were included. Criteria for exclusion were steroid treatment or endocrine disease. Blood chemistry, urinalysis, vitamin D metabolites, parathormone (PTH), and PN composition values at the date of each DEXA measure were retrospectively collected from clinical files.Results. – Twenty-one children on cyclic LTPN were studied. Underlying disease was short bowel syndrome (SBS, 16) and functional gut failure (FGF, 5). Forty-six DEXA were performed, with a mean two DEXA/patient (1–6). At the date of DEXA, ages ranged from 2 to 7 years and PN duration was 83 ± 38 months. The mean residual SB length (SBL) was 32 cm. Nutrient supplies matched recommendations for pediatric PN. Children presented neither with fractures nor with bone pains, from PN onset. The mean lumbar spine Z score for BMD was –0.71 ± 1.44 S.D. (whatever PN duration or underlying disease). No statistical relation existed between BMD and age at PN onset, PN duration or SBL in case of SBS. No biological abnormalities were observed at routine follow-up.Conclusions. – This study provides both cross-sectional and longitudinal Z score values in children while still on LTPN. Moderate MBD exists in children on LTPN, while it is clinically latent. Therefore, DEXA seems to be the only tool usable for both diagnosis and follow-up of MBD in children.
Nutrition Clinique Et Metabolisme - NUTR CLIN METAB. 01/2004; 18(2):66-72.
[Show abstract][Hide abstract] ABSTRACT: Large intestinal fermentation and nutrient metabolism in colonocytes were investigated in a rat model of enteral feeding. Male Wistar rats (240-280 g) were submitted to 7 or 14 days of treatment: intragastric feeding (elemental formula) versus oral feeding (isocaloric and isonitrogenous diet, containing 5% purified cellulose) in the control group. Fermentation products and bacterial populations were analyzed in cecal contents. Colonic cells were isolated and tested for their capacities to metabolize [1-(14)C] butyrate and [U-(14)C]glutamine. After 7 days of enteral nutrition, short-chain fatty acid concentrations represented 52% of those measured in the control group, but colonocyte metabolism remained unchanged. After 14 days of enteral nutrition, short-chain fatty acid concentrations were still decreasing, although bacterial counts remained unchanged. In parallel, ammonia and lactate concentrations were significantly increased. The capacities to utilize butyrate and glutamine in colonocytes were only slightly affected. However, there was a dramatic increase in the ratio of beta-OH-butyrate to acetoacetate fluxes, suggesting a more reduced redox mitochondrial state associated with enteral feeding.
Digestive Diseases and Sciences 08/2003; 48(7):1339-45. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition.
Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition.
The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1).
Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.
Journal of Pediatric Gastroenterology and Nutrition 05/2003; 36(4):448-53. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In children who depend on long-term parenteral nutrition (PN), a major goal is to obtain optimal growth. The aim of this retrospective study was to analyze growth in children on long-term cyclic nocturnal home PN, over at least 8 years before puberty. Nine boys and 7 girls were studied. Their mean age at the time of study was 11 years with a mean PN duration of 10.5 (8.6-16.4) years. Diseases were short bowel syndrome (5), intractable diarrhea (4), chronic intestinal pseudo-obstruction (4) and long segment Hirschsprung's disease (3). In each child, periods of at least 2 years were analyzed: either periods of regular growth (R: height gain >50th percentile), or slow growth (S: height gain < or =25th percentile). Results were expressed as mean +/- SD. Comparisons were performed using either Student's test for unpaired data or Wilcoxon's test for paired data. PN provided a mean of 224 +/- 80 mg nitrogen/kg/day and 43 +/- 14 kcal/kg/day equivalent to 50% of recommended supplies. At the time of study, the population presented with weight (W) = -0.7 +/- 0.8 SD and height (H) = -1.5 +/- 1.3 SD. The difference between W and expected W for H (W/H) was significant (p < 0.002). W/H ratio was 105 +/- 11%. For the total PN duration, weight gain was +0.2 +/- 1.5 SD and height loss was -0.75 +/- 1.4 SD. An excess weight gain occurred in parallel with the deflection of height gain. Of the 16 children, regular prepubertal growth was achieved in 4 only. The other 12 showed alternate periods of R and S. In 8 of them, 26.5 years of R and 33.5 years of S were compared, each child being his own control. PN nitrogen and energy supplies were significantly higher during R periods than during S periods. In the absence of any disease or treatment explaining the failure to thrive, inadequate PN supplies, especially in terms of nitrogen supply, are thought to be responsible for a negative nitrogen balance and slowed growth. In case of any deflection away from the individual growth curve, it is recommended to adjust the PN supply early, especially nitrogen supply.
Hormone Research 01/2002; 58 Suppl 1:2-6. · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present selected XAS applications, focused towards practical hospital questions of drug administration and bioavailability, where the technique is driven up to its limits of sensitivity. i) XAS was used to study the interactions between the components of parenteral nutrition solutions, in particular zinc and aminoacids, possibly modifying their bioavailability. ii) We studied by EXAFS a series of binary and ternary copper-aminoacid complexes, in view of the development of an efficient oral drug against copper deficiencies in Menkes disease. iii) EXAFS and XANES analysis allowed us to characterise the solution form of a new arsenic containing drug against leukaemia. In parallel to the XAS measurements, we analysed trace elements levels along patients' hairs, using X-ray fluorescence excited by synchrotron radiation. The measurements along the hair allow for a monitoring of essential trace elements during therapy.
[Show abstract][Hide abstract] ABSTRACT: A new intravenous lipid emulsion (ILE) prepared from a mixture of soybean and olive oils contains only long-chain triacylglycerols, with a low proportion (20%) of polyunsaturated fatty acids and 60% monounsaturated fatty acids.
The goal of this randomized, double-blind clinical trial was to assess in children the efficacy and safety of this new ILE compared with a control group receiving a soybean-oil emulsion.
Eighteen children received for 2 mo 24% of nonprotein energy (1.80 g kg (-)(1) d(-)(1)) either as the new ILE or a soybean oil-based emulsion. Assessments were performed on days -30, 0, 30, and 60 and the changes (day 60 - day 0) assessed by analysis of variance.
There were no significant differences in triacylglycerol, apolipoproteins A-I and B, or HDL cholesterol between the 2 groups, whereas total and LDL cholesterol were higher in the soybean oil group on day 60. The pattern of 20:4n-6 in erythrocyte membranes did not change significantly, nor did the ratio of 20:3n-9 to 20:4n-6. On day 60, 18:1n-9 was significantly higher in the olive oil group, the ratio of Sigma(n)-6 > C(18) + 18:3n-6 to 18:2n-6 was 2.20 +/- 0.09 in the olive oil group and 1.33 +/- 0.16 in the soybean-oil group, and Sigma(n)-3 > C(18) was 3.83 +/- 0.30 in the olive oil group and 4. 03 +/- 0.33 in the soybean-oil group. The peroxidation index was lower after the olive oil treatment.
The olive oil-based emulsion was well tolerated, maintained a normal EFA status, and may be more suitable for prevention of lipid peroxidation than the soybean-oil-based emulsion.
American Journal of Clinical Nutrition 09/1999; 70(3):338-45. · 6.50 Impact Factor