Taurine depletion in very low birth weight infants receiving prolonged total parenteral nutrition: role of renal immaturity

In a prospective, controlled study, plasma and urinary taurine concentrations were determined weekly, between postnatal weeks 3 and 18, in (1) seven sick infants (gestational age less than 28 weeks, birth weight less than or equal to 1000 gm) who received a taurine-free total parenteral nutrition solution for 32 to 49 days (group P) and who subsequently were formula fed and (2) eight sick infants matched by gestational age and birth weight, who received formula or human milk from day 3 to 4 of life (group E). Ten healthy full-term infants ranging in age from 1 to 18 weeks and fed with formula provided normal values (group C). Significantly lower mean plasma taurine values (range 1.59 to 3.43 mumol/dl) were found between postnatal weeks 3 and 7 in group P compared with group E (range 5.54 to 6.97 mumol/dl) and with group C (5.6 +/- 0.34 mumol/dl). After initiation of feeding, plasma taurine concentrations in group P increased to normal. Markedly elevated values of mean fractional excretion of taurine, 38% to 56%, were found between weeks 3 and 5 in group P and E compared with group C (15.5 +/- 3.2%). In contrast, during the same period, low urinary taurine values (4.9% to 6.7%) were found in two larger, older infants receiving total parenteral nutrition whose plasma taurine values were in the normal range. After week 5, urinary taurine values were in the control range in all groups. We conclude that the absence of taurine in total parenteral nutrition solutions administered to very low birth weight infants and the limited ability of the immature kidney to adapt to low taurine intake by "up-regulation" of tubular taurine reabsorption may result in depleted taurine body pools during the first weeks of life. This inability to conserve taurine by the immature nephron could potentially have a deleterious effect on the developing brain and retina in these infants, and indicates a possible need for taurine supplementation.     

Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of taurine metabolism in beagle pups: effects of taurine-free total parenteral nutrition

In beagle pups (from 5 to 84 days of age), plasma taurine concentration decreased between 5 and 21 days of age with no change thereafer; cerebral taurine concentration decreased throughout the period of study but cerebral taurine content increased between 5 and 21 days of age; hepatic taurine content (but not concentration) increased throughout. Both hepatic cysteinesulfinic acid decarboxylase (CSAD) activity and the concentration of taurine-conjugated bile acid of gallbladder bile increased during the period of study. Plasma and cerebral taurine pools were not affected by taurine-free total parenteral nutrition (TPN). Hepatic taurine content was also not affected, but taurine concentration decreased; however, this change resulted from an increase in hepatic size. Hepatic CSAD activity of animals that received TPN was greater than that of 35-day control animals while the concentration of taurine-conjugated bile acids in the gallbladder bile was less. Although plasma taurine concentration was not affected by intravenous glucose therapy, both the hepatic taurine concentration and content of these animals were less than those of 35-day control animals. Cerebral taurine concentration of these animals, on the other hand, were greater. Hepatic CSAD activity of the animals that received only intravenous glucose was similar to that of controls, but the taurine-conjugated bile acid concentration in the gallbladder bile, like that of animals that received TPN, was less than that observed in 35-day control animals.     

Taurine concentrations in plasma, blood cells, and urine of children undergoing long-term total parenteral nutrition

Taurine concentrations in plasma, platelets, lymphocytes, granulocytes, erythrocytes, and urine were measured in 19 children who were undergoing long-term home parenteral nutrition for 27.4 +/- 7.1 (SEM) months. The parenteral solutions contained methionine, but not taurine or cysteine. The patients' plasma, platelet, and urine taurine concentrations were significantly reduced to 54, 48, and 16%, respectively, of the values from normal children of similar ages. The most significant reductions in plasma and platelet taurine concentrations were observed in the children who were estimated to absorb less than 5% of their daily calorie needs from the enteral tract. Lymphocyte and erythrocyte taurine levels tended to be lower but were not significantly different from those in normal children. The patients' plasma methionine and cystine levels were not different from normal. There was a direct correlation between plasma and platelet taurine concentrations and between plasma and urine taurine. Both plasma and platelet taurine tended to be directly correlated with age and, after the 1st yr of total parenteral nutrition, with the duration of total parenteral nutrition therapy.     

Insulin-like growth factor I (somatomedin C) in premature infants on total parenteral nutrition. Relations with nutritional status and protein-energy intakes]

Insulin-like growth factor I (IGF I) is like prealbumin and transferrin a marker of nutritional status. Its level increases with gestational age. The levels of IGF I (96 times), transferrin (86 times) and prealbumin (69 times) were measured in blood samples from 26 premature infants aged 8 to 78 days (gestational age: 28 to 34 weeks, birth weight: 840 to 1,800 g). At the time of sampling, all the infants were on total parenteral nutrition (360 +/- 42 kJ/kg/day and 2.5 +/- 0.3 g of proteins/kg/day). The results were analysed with reference to anthropometric parameters (weight, height, head circumference, skinfolds and arm circumference). There was no correlation between plasma IGF I and anthropometric measurements. There were significant correlations between IGF I and transferrin (p less than 0.01), prealbumin (p less than 0.05), protein intake (p less than 0.01) an energy intake (p less than 0.05). Plasma IGF I increased at the end of the first week of parenteral nutrition in all the 5 infants having initial low values. The plasma IGF I was not correlated with the duration of parenteral nutrition in the 26 infants after the second week of nutrition. IGF I measurement is useful for evaluating the protein nutritional status of premature infants on total parenteral nutrition.     

Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition

A mixture of amino acids designed to maintain normal plasma amino acid concentrations of infants and children requiring parenteral nutrition was evaluated in 40 infants and children receiving only parenteral nutrients (2.39 +/- 0.26 g/kg/d of amino acids and 110.3 +/- 10.4 kcal/kg/d) for five to 21 days. The children ranged in weight from 2.0 to 12.6 kg (median weight, 3.83 kg; fifth to 95th percentile, 2.06 to 11.1 kg) and in age from 1 week to 43.6 months (median age, 2.7 months; fifth to 95th percentile, 0.2 to 25.3 months). Mean weight gain was 11.0 +/- 5.0 g/kg/d; mean nitrogen balance was 242 +/- 70 mg/kg/d. Plasma concentrations of all amino acids except tyrosine were within the normal range (ie, within the 95% confidence limits of the two-hour postprandial plasma concentrations observed in 30-day-old, healthy, normally growing, breast-fed, term infants) throughout the period of study. Mean prestudy and poststudy serum total protein, albumin, and transthyretin (prealbumin) concentrations were not significantly different. However, plasma transthyretin concentration increased in all children with low prestudy concentrations. Mean poststudy serum total bilirubin concentration of the total population was not different from the mean prestudy concentration. This was true also for the 31 children who received the parenteral amino acid mixture for more than ten days. In contrast to the expected 30% to 50% incidence of cholestasis, only one of these 31 experienced an unexplained increase in serum total bilirubin concentration during study, suggesting that normalizing plasma amino acid concentrations and/or providing taurine during parenteral nutrition may decrease the incidence of cholestasis associated with this therapy.     

Nosocomial bacteremias in pediatrics]

OBJECTIVES: To identify pathogenic microorganisms responsible for hospital-acquired bloodstream infections and to evaluate the associated risk factors in pediatric units, in a case-control study over 30 months from January 1st 1997 to June 30th 1999. RESULTS: Forty-six of 855 (5.4%) positive blood cultures were attributed to nosocomial infections. They were related to 32 infectious episodes in 28 patients hospitalized for more than 48 hours. The incidence rate was 0.11 per 100 admissions. Gram-positive cocci (n = 14; 38.8%) were the most frequently isolated pathogens (7 cases of Staphylococcus aureus, 5 of coagulase-negative staphylococci), followed by enterobacteria (n = 9; 25%), Pseudomonas aeruginosa (n = 5; 13.8%) and yeasts (n = 5; 13.8%). The major risk factors for hospital-acquired bloodstream infections were: length of stay before positive blood culture (32 +/- 51 days in cases vs 15 +/- 43 days in controls, p < 0.01), presence of central venous catheter [odds ratio (OR): 6.05, 95% confidence interval (CI): 1.87-20.42], number of days with central venous catheter (p < 0.001) and parenteral nutrition (OR: 9.44, 95% CI: 2.03-50.05). CONCLUSION: Central venous catheter use, length of stay, parenteral nutrition and particularly intravenous lipids are major risk factors for the acquisition of bloodstream infection in hospitalized children.     

Essential fatty acid status of the premature infant during short-term fat-free parenteral nutrition

This study was designed to evaluate the effect of fat-free parenteral nutrition on the essential fatty acid status of a group of stable premature infants during the first 10 days of life. Nine infants had a gestational age of less than 32 weeks (Group 1), and 10 infants, 32-34 weeks (Group 2). Five of nine infants in Group 1 and two of 10 infants in Group 2 developed essential fatty acid deficiency (EFAD) (triene/tetraene ratio greater than 0.4). In three infants, EFAD was present by 5 days of age; and in four, between 5 and 10 days of age. The difference in frequency of EFAD between Groups 1 and 2 is statistically significant (p less than 0.05). The development of EFAD as a function of postnatal age could be predicted using a simple regression, y = -0.14 + 0.07x (r = 0.64, p less than 0.0001), where y represents the triene/tetraene ratio and x the postnatal age in days. We conclude that (a) EFAD may develop rapidly in the premature infant; (b) the more immature the infant, the greater the risk of EFAD; (c) the degree of EFAD increases with the duration of fat-free parenteral nutrition.     

Taurine requirement of premature infants in parenteral nutrition]

The aim of our studies was to clarify, which dose of taurine should be added to amino acid solutions, in order to achieve plasma levels in premature infants as they are found during nutrition with mother's milk. In 22 premature infants born in the 30th-35th week of gestation plasma taurine levels during parenteral nutrition were measured on the 5th-9th day of life before and after infusing an amino acid solution supplemented with taurine. For analysis the principle of chromatographical ion exchange was applied. The requirement of taurine was calculated by means of a linear regression between supply and blood level. The mean plasma taurine levels before substitution were 88.7 mumol (95%-range of tolerance: 32.8-240 mumol/l). In premature infants with cerebral haemorrhages significantly higher plasma taurine levels were observed. Continuous parenteral taurine supply of approximately 0.05 g/kg/day was able to raise the taurine level by about 70 mumol/l, which caused a plasma taurine level of above 100 mumol/l in any case. During parenteral nutrition it is possible to achieve taurine levels as high as in breastfed neonates by substituting taurine at an amount of 0.05 g taurine per kg body weight.     

Lipid clearing in premature infants during continuous heparin infusion: role of circulating lipases

The nature of the lipases released into the circulation during low level continuous infusion of heparin (1 unit/ml total parenteral nutrition) and after bolus heparin injection (10 units/kg) was investigated in a group of 11 low birth weight infants (gestational age 27-34 wk, and postnatal age of 7-26 days) receiving total parenteral nutrition with Intralipid (0.5 g/kg). Hepatic lipase and extra-hepatic lipoprotein lipase were differentiated with the aid of an antibody specific for human hepatic lipase. The data show that continuous low level heparin infusion leads to a constant baseline postheparin lipolytic activity of 0.77 +/- 0.18 mumol free fatty acids released per milliliter serum per hour. Bolus heparin injection leads to peak lipolytic activity levels of 3.77 +/- 0.46 mumol free fatty acids per milliliter serum per hour, 10 min after injection. About two-thirds of the total postheparin lipolytic activity was of the hepatic type during low level continuous infusion or after bolus injection of heparin.     

Thiamine, riboflavin, pyridoxine, and vitamin C status in premature infants receiving parenteral and enteral nutrition

BACKGROUND: There is a paucity of data about water soluble vitamin status in low birthweight infants. Therefore, the authors' objective was to assess current feeding protocols. METHODS: The authors measured serum concentrations for riboflavin, pyridoxine, and vitamin C and functional assays for thiamine and riboflavin longitudinally in 16 premature infants (birthweight, 1,336 +/- 351 g; gestational age, 30 +/- 2.5 weeks) before receiving nutrition (time 1, 2 +/- 1 days), during supplemental or parenteral nutrition (time 2, 16 +/- 10 days) and while receiving full oral feedings (time 3, 32 +/- 15 days). In plasma, vitamin C was measured colorimetrically, and riboflavin and pyridoxine were measured using high-performance liquid chromatography. The erythrocyte transketolase test as a functional evaluation of thiamine and the erythrocyte glutathione reductase test for riboflavin were measured colorimetrically. RESULTS: At time 1, nutrient intake of vitamins were negligible because infants were receiving intravenous glucose and electrolytes only. Intakes differed between time 2 and time 3 for thiamine (510 +/- 280 and 254 +/- 115 microg. kg-1. d-1, respectively), riboflavin (624 +/- 305 and 371 +/- 193 microg. kg-1. d-1, respectively), and pyridoxine (394 +/- 243 and 173 +/- 85 microg/100 kcal, respectively), but not for vitamin C (32 +/- 17 and 28 +/- 12 mg. kg-1. d-1, respectively). Blood levels at times 1, 2, and 3 were for thiamine (4.9 +/- 2.7%, 3.3 +/- 6.6%, and 4.1 +/- 9% erythrocyte transketolase test, respectively), riboflavin (0.91 +/- 0.31, 0.7 +/- 0.3, 0.91 +/- 0.18 erythrocyte glutathione reductase test, respectively), riboflavin (19.5 +/- 17, 23.3 +/- 8.6, 17.6 +/- 10 ng/mL, respectively), pyridoxine (32 +/- 25, 40 +/- 16, 37 +/- 26 ng/mL, respectively), and vitamin C (5.2 +/- 3, 5 +/- 2.2, 10 +/- 5 microg/mL, respectively) and did not differ at those times. CONCLUSIONS: Current intakes of these vitamins, except for possibly vitamin C, during parenteral and enteral nutrition seem to result in adequate plasma concentrations and normal functional indices.     

Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion

Very low birth weight infants have little storage of hepatic retinol and are, therefore, highly dependent upon an exogenous supply. The recent association between low serum retinol level and bronchopulmonary dysplasia and the persistently low serum levels of retinol during total parenteral nutrition prompted a prospective study to evaluate serial changes in serum retinol levels during 1 month of total parenteral nutrition (retinol dose 455 micrograms/d) and again during 1 month of total enteral feeding (retinol dose 200 to 300 micrograms/d) in the same infants. Infants were divided into two groups. Group 1 consisted of infants weighing less than 1,000 g (n = 24) and group 2 consisted of infants weighing 1,000 to 1,500 g (n = 17). Although initial mean levels of retinol were similar in both groups (14.8 +/- 0.9 and 13.5 +/- 0.7 micrograms/dL), there was wide variation between infants. In group 1 infants, there was a significant (P less than .01) decline in retinol level by the second week of life (to 9.2 +/- 1 micrograms/dL), which persisted during total parenteral nutrition, but increased to 13.4 +/- 2 after 1 week of enteral feeding. This level was maintained throughout enteral feeding. In group 2 infants, there was no significant change in serum retinol level throughout the study. During total parenteral nutrition, several infants had retinol levels below 10 micrograms/dL, a level associated with signs of retinol deficiency in older children. Because losses of retinol are known to occur in smaller volume total parenteral nutrition solutions, it was speculated that losses of retinol in our patients were due to retinol losses in the total parenteral nutrition delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma 1.25-dihydroxyvitamin D concentrations in preterm infants

1.25-Dihydroxyvitamin D concentrations were measured in 10 preterm infants (mean gestational age 29 weeks, range 26-32; mean birthweight 1226 g, range 980-1700). Total parenteral nutrition was begun after birth and partial enteral feeding was started at 1 week of age. Total enteral feeding was achieved at a mean age of 26 days (range 16-47). The daily vitamin D3 intake was about 400 I. U. No clinical, chemical or radiological signs of rickets were observed. The mean 1.25-dihydroxyvitamin D concentration +/- SEM was 103.2 +/- 24.0 pmol/l at 1 week (range 9.6-252.0), 141.6 +/- 26.4 at 3 weeks (range 31.2-324.0), 153.6 +/- 21.6 at 6 weeks (range 67.2- 256.8), 165.6 +/- 24.0 at 9 weeks (range 74.4-307.2) and 153.6 +/- 21.6 at 12 weeks (range 76.8-268.8) postnatal age. The mean values at 6, 9 and 12 weeks were significantly higher (p resp. less than 0.01, less than 0.002 and less than 0.005) than in adults (88.8 +/- 7.2; n = 27). 1.25-Dihydroxyvitamin D concentrations were highly variable and did not correlate with 25-hydroxyvitamin D concentrations, plasma calcium and phosphorus concentrations and plasma alkaline phosphatase levels, nor with illness nor postnatal age. The data demonstrate that preterm infants are capable of producing high plasma levels of 1.25-dihydroxyvitamin D.     

Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth-weight infants

BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive enteral and parenteral nutriture that provides greater daily riboflavin (vitamin B2) than does term infant nutriture, and elevated plasma riboflavin develops in these infants after birth. The purpose of this study was to measure plasma and urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition. Our hypothesis was that elevated plasma riboflavin develops in VLBW infants because of high daily intake and immature renal riboflavin elimination. METHODS: Eighteen clinically healthy VLBW infants received parenteral nutrition and preterm infant formula during the first postnatal month. On postnatal days 10 and 28, the infants received specially prepared riboflavin-free enteral and parenteral nutrition for the 24-hour study period. Serial collections of plasma were made at time 0 and at 12 and 24 hours. Urine was collected continuously for the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin concentration. RESULTS: During the 24-hour riboflavin-free study period on postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/- SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the 24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5 hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased 40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral nutrition and preterm infant formula had elevated plasma riboflavin on postnatal days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin elimination was greater on postnatal day 28 than on postnatal day 10. Plasma riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of plasma and urine riboflavin in VLBW infants suggests a lower daily intake would maintain plasma riboflavin close to normal.     

Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition in infants and children. I. Blood levels of water-soluble vitamins

This study represents the first attempt to evaluate the response to the only intravenous vitamin preparation (MVI Pediatric) for infants and children receiving total parenteral nutrition. Eighteen preterm infants (group 1), 26 term infants and children receiving total parenteral nutrition for 2 to 4 weeks (group 2A), and eight infants and children receiving total parenteral nutrition for 3 to 6 months (group 2B) were studied. Term gestation infants and children up to 11 years of age received daily vitamin doses that approximated the 1974 Recommended Dietary Allowances and coincided with the 1975 American Medical Association Nutrition Advisory Group total parenteral nutrition dosage guidelines for children weighing more than 10 kg. Preterm infants received 65% of these dosages. RBC transketolase (vitamin B1), glutathione reductase (B2), and glutamic oxaloacetic transaminase (B6) activities were maintained at normal levels, and niacin levels were maintained within the reference range (7.1 +/- 0.32 micrograms/mL) in all study patients. Pantothenate, biotin, and ascorbate were maintained at reference levels in groups 2A and 2B. In group 1, ascorbic acid was increased significantly during treatment from 1.53 +/- 0.16 to 3.60 by seven days and to 2.54 +/- 0.62 by day 28 of treatment (reference normals = 0.99 +/- 0.1 mg/dL). RBC folate was maintained within the reference range of 411 +/- 76 pg/mL; however, pantothenate and biotin levels increased significantly to more than 2 SD above reference values during treatment, and vitamin B12 levels, which were above the reference range initially, were maintained at more than 2 SD above the reference range throughout treatment. The elevation in vitamin B12 was seen in both group 1 and 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of total parenteral nutrition on lipase activity in the stomach of very low birth weight infants

Lipase activity was quantitated in gastric aspirates of 7 premature infants (gestational age 24-29 weeks) during periods of total parenteral nutrition (TPN), mixed parenteral nutrition and gavage feeding or exclusive gavage feeding. The infants were studied from birth until the establishment of exclusive gastric gavage feeding. Lipase activity in gastric aspirates (quantitated by the hydrolysis of 3H-triolein at pH 4.2 and expressed in nmol 3H-oleic acid released/min/ml gastric aspirate) did not differ significantly as a function of mode of feeding: 570 +/- 235 during TPN, 260 +/- 145 during mixed parenteral nutrition and gavage feeding, and 374 +/- 149 during exclusive gastric gavage feeding. The data suggest that, contrary to the intestine and pancreas, the digestive function of the stomach is not impaired during TPN in the very preterm infant.     

Renal function of children receiving long-term parenteral nutrition

Renal function was assessed in 13 children at a mean (+/- SD) age of 9 +/- 4.9 years who had been receiving total parenteral nutrition for 7.9 +/- 4.1 years. All children had normal blood pressure, urinary sediment, and serum creatinine concentrations (58.3 +/- 1.0 mumol/L). Glomerular filtration rate was measured by plasma clearance of diethylenetriaminepentaacetic acid labeled with indium 111. All 13 children had decreased glomerular filtration rate (65.5 +/- 11.9 ml/min per 1.73 m2; range 49.5 to 83.7). Creatinine clearance was 69.1 +/- 10.9 ml/min per 1.73 m2. No tubular damage, as assessed by beta 2-microglobulinuria, was detectable. Renal ultrasonography showed normal architecture with no evidence of nephrocalcinosis in all subjects. The kidney size was normal in seven children; six had reduced (less than -1 SD) size. No relationship was seen between the true glomerular filtration rate and diagnosis, number of episodes of infections, or antibiotics used. The duration of total parenteral nutrition was inversely correlated with the true glomerular filtration rate (r = -0.66, p less than 0.01). The decrease in glomerular filtration rate was not related to the underlying disease or to the nephrotoxic drugs used; the mechanism was not identified. We conclude that long-term total parenteral nutrition is associated with a decrease in glomerular filtration rate.     

A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric crohn disease

OBJECTIVES: To evaluate the efficacy and toxicity of infliximab in children with severe Crohn disease (CD), the authors prospectively monitored 21 children aged 15 +/- 2 years with severe CD who they treated with infliximab (5 mg/kg) on days 0, 15, and 45. One patient received only one injection. Eighteen patients were corticosteroid dependent, and 6 were receiving parenteral nutrition. Three patients were corticoid resistant (1 mg/kg/d >15 days). Sixteen had perianal disease. RESULTS: The Harvey-Bradshaw index (HB) decreased from 8 +/- 3 on day 0 to 1 +/- 2 on day 45 (P = 0.001). The inflammation factors decreased (P = 0.001), and albumin increased (P = 0.002). Nineteen children were in complete remission (HB < 4) on day 45, and 2 had improved (HB = -6 points). Tumor necrosis factor-alpha (TNFalpha) in the stools (n = 16) decreased (P = 0.04). All perianal fistulas (n = 12) were closed by day 90. Fourteen of 21 patients had stopped taking steroids at 3 months, and all had stopped parenteral nutrition. Growth velocity was significantly greater after infliximab administration (Z score, +0.5) than before (-0.45; P = 0.004). Nineteen of 21 patients had relapsed (90%) at 1 year despite continued immunosuppressors. Seven had surgery because of an uncontrolled relapse ( 5), stenosis ( 1), or fistula ( 1). Six patients developed antinuclear antibodies (1/40-1/640e), and two had anti-DNA antibodies. Epstein-Barr virus (EBV) polymerase chain reaction (PCR) values increased (>100-fold) in eight patients. One child developed an anaphylactic reaction to the medication, and one had a catheter-related sepsis. CONCLUSION: Infliximab produces spectacular results for children with severe CD and is well tolerated. However, its effect is transitory for many (90%), with frequent relapses despite continued immunosuppressors. Long-term management with infliximab should be tested despite its worrying side effects.     

Discordant amino acid profiles in monochorionic twins with twin-twin transfusion syndrome

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0. 001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 +/- 64 versus 396 +/- 23 microM; p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.     

Randomised controlled study of clinical outcome following trophic feeding

AIMS: To determine the effect of trophic feeding on clinical outcome in ill preterm infants. METHODS: A randomised, controlled, prospective study of 100 preterm infants, weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition, was performed. Group TF (48 infants) received trophic feeding from day 3 (0.5-1 ml/h) along with parenteral nutrition until ventilatory support finished. Group C (52 infants) received parenteral nutrition alone. "Nutritive" milk feeding was then introduced to both groups. Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks, sepsis incidence, liver function, milk tolerance, duration of respiratory support, duration of hospital stay and complication incidence. RESULTS: Groups were well matched for birthweight, gestation and CRIB scores. Infants in group TF had significantly greater energy intake, mean difference 41.4 (95% confidence interval 9, 73.7) kcal/kg p=0.02; weight gain, 130 (CI 1, 250) g p = 0.02; head circumference gain, mean difference 0.7 (CI 0.1, 1.3) cm, p = 0.04; fewer episodes of culture confirmed sepsis, mean difference -0.7 (-1.3, -0.2) episodes, p = 0.04; less parenteral nutrition, mean difference -11.5 (CI -20, -3) days, p = 0. 03; tolerated full milk feeds (165 ml/kg/day) earlier, mean difference -11.2 (CI -19, -3) days, p = 0.03; reduced requirement for supplemental oxygen, mean difference -22.4 (CI-41.5, -3.3) days, p = 0.02; and were discharged home earlier, mean difference -22.1 (CI -42.1, -2.2) days, p = 0.04. There was no significant difference in the relative risk of any complication. CONCLUSIONS: Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition.