Laurie Reyen

Excessive chromium intake in children receiving total parenteral nutrition

Various expert bodies have recommended that the daily parental intake of chromium in children receiving total parenteral nutrition (TPN) should be 0.20 micrograms/kg. To test whether this recommendation is appropriate, we assessed chromium intake, serum chromium concentrations, and renal function in 15 children receiving TPN. The median duration of TPN use was 9.5 (range 1.3-14) years. The childrens glomerular filtration rate (GFR), measured by plasma clearance of indium-111-DTPA was lower than that of non-TPN controls (70 [SD 17] vs 110 [10] ml/min per 1.73 m2). The daily chromium intake averaged 0.15 (0.09) micrograms/kg daily but the serum chromium concentration was 20 (4 to 42) times higher than that of the controls (2.1 [1.2] vs 0.10 [0.03] micrograms/l; p less than 0.0001). GFR was significantly inversely correlated with serum chromium concentration (r = -0.60, p less than 0.02), daily chromium intake (r = -0.69, p less than 0.01), cumulative parenteral chromium intake (r = -0.72, p less than 0.01), and TPN duration (r = -0.52, p less than 0.05). We discontinued chromium supplementation of TPN solutions and reassessed the children a year later. Contaminating chromium concentrations were 1.0-1.8 micrograms/l in TPN solutions and 0.9 micrograms/l in fat emulsions. Drinking water contained 4.3-5.7 micrograms/l. Thus, the chromium intake without supplementation was only 0.05 (0.01) micrograms/kg daily. The mean serum chromium concentration fell to 0.50 (0.30) micrograms/l but was still significantly higher than that in the controls (p less than 0.01). The GFR did not change significantly (65 [14] ml/min per 1.73 m2). No patient has shown signs of chromium deficiency. Although our patients were receiving less than the recommended chromium intake during supplementation, their high serum concentrations suggested excessive intake. The recommended parenteral chromium intake for children should be lowered.

Pediatric Intestinal Failure–Associated Liver Disease Is Reversed With 6 Months of Intravenous Fish Oil

BACKGROUND Studies have suggested that when intravenous (IV) soybean oil (SO) is replaced with fish oil (FO), direct hyperbilirubinemia is more likely to resolve. The necessary duration of FO has not been established. This study seeks to determine if 24 weeks of FO is an effective and safe therapy for intestinal failure-associated liver disease (IFALD). MATERIALS AND METHODS This is a clinical trial using patients with IFALD between the ages of 2 weeks and 18 years. SO was replaced with FO (1 g/kg/d) in 10 patients who were receiving most of their calories from parenteral nutrition (PN). Patients were compared with 20 historic controls receiving SO. SO for both groups was prescribed by the primary medical team at variable doses. The primary outcome was time to reversal of cholestasis. Secondary outcomes were death, transplant, and full enteral feeds. Safety measurements included growth, essential fatty acid deficiency, and laboratory markers to assess bleeding risk. RESULTS The Kaplan-Meier method estimated that 75% in the FO group would experience resolution of cholestasis by 17 weeks vs 6% in the SO group (P < .0001). When compared with the SO group, the FO group had decreased serum direct bilirubin concentrations at weeks 8 (P = .03) and 12, 16, 20, and 24 weeks (P < .0001). Although length z score at the end of the study increased in the FO group compared with baseline (P = .03), there were no significant differences in other outcomes. CONCLUSIONS A limited duration of FO appears to be safe and effective in reversing IFALD.

Long-term nutrition and predictors of growth and weight gain following pediatric intestinal transplantation.

Background. Advances in intestinal transplantation (ITx) have resulted in improved survival and the opportunity to examine nutritional outcomes. The aim of this study was to describe detailed, long-term nutritional results and identify positive predictors of growth and weight gain following pediatric ITx. Methods. A single-center retrospective, Institutional Review Board-approved review of a prospective database was conducted. Inclusion criteria were ITx recipients 18 years or younger with survival of 6 months or more. Outcomes included anthropometric measurements and biochemical markers at 6, 12, 24, 36, and 48 months post-ITx. More than 25 ITx-related variables were analyzed as potential predictors of growth and weight gain. Statistical analysis was performed using chi-square test, t test, and analysis of variance. Results. Between November 1991 and April 2007, 50 children received 55 ITx; 33 patients met eligibility criteria. Median age at ITx was 2.2 years, follow-up time was 3.8 years, and time from ITx to cessation of total parenteral nutrition was 31 days. The most common micronutrient deficiencies post-ITx were zinc, iron, and copper. Serum protein levels improved significantly over time. Weight gain occurred within 6 months and vertical growth within 12 months, although limited catch-up growth was seen. Early predictors of weight gain and growth included shorter hospitalization and absence of rejection. Long-term predictors were low steroid dosage, infrequent hospitalization, and the use of peptide-based formulas. Conclusions. This represents one of the largest and most comprehensive long-term studies on nutritional outcomes in pediatric ITx. Overall, positive growth and weight gain were seen as were micronutrient deficiencies. Numerous long-term nutritional challenges exist which require a multidisciplinary approach and future prospective studies.

Chronic liver disease in children on long‐term parenteral nutrition

Use of long‐term total parenteral nutrition (TPN) is often presumed to be associated with serious hepatic dysfunction. In this retrospective study, we reviewed the complete charts of patients who had received TPN for more than 2.5 years, starting in infancy or childhood, for evidence of liver dysfunction. There were 16 male and 10 female patients with a total of 254.5 patient years on TPN. Seventeen patients have been on TPN since birth or early infancy. Thirteen of 26 patients derive ≥90% of their calorie intake from TPN. Six patients had hepatomegaly; two of them also had splenomegaly. Twenty‐one patients had normal transaminases, nine have had past episodes of raised enzymes ranging from 2.5 to 7.5 times normal. Seventeen patients always had normal bilirubin levels, five had past episodes of hyperbilirubinaemia, while four patients had persistently raised bilirubin levels (range 1.5–20.7 g/dL). Alkaline phosphatase was normal for age in all patients except two. Hepatic synthetic function, as measured by albumin, pre‐albumin levels and prothrombin time, was within the normal range in all patients except one. Liver biopsies were performed in eight patients. Two biopsies showed cirrhosis, one showed chronic active hepatitis (CAH) with cholestasis, two patients had fibrosis, one showed cholestasis and two biopsies were normal. One patient with cirrhosis and one with CAH were positive for hepatitis C antibody. Another asymptomatic patient was positive for hepatitis B. Only the patient with CAH had hepatic decompensation. We conclude that clinical hepatic failure is uncommon in our group of patients on long‐term TPN for 2.5 years or more. Cirrhosis and fibrosis, when found, could not be solely attributed to TPN.

Iodine supplementation in children receiving long-term parenteral nutrition.

In 18 children receiving long-term total parenteral nutrition (TPN) without iodide supplements, thyroid function test results were normal but serum iodide levels were greater than in control subjects (p less than 0.01). Iodine contamination of TPN solutions and fat emulsions accounted for only half of the recommended parenteral intake. Skin absorption of topical iodinated disinfectant may explain the adequate, if not excessive, iodine intake. We conclude that iodine is an unnecessary supplement in TPN solutions.

Race affects outcome among infants with intestinal failure.

Objective: Intestinal failure (IF) is a rare, devastating condition associated with significant morbidity and mortality. We sought to determine whether ethnic and racial differences were associated with patient survival and likelihood of receiving an intestinal transplant in a contemporary cohort of children with IF. Methods: This was an analysis of a multicenter cohort study with data collected from chart review conducted by the Pediatric Intestinal Failure Consortium. Entry criteria included infants ⩽12 months receiving parenteral nutrition (PN) for ≥60 continuous days and studied for at least 2 years. Outcomes included death and intestinal transplantation (ITx). Race and ethnicity were recorded as they were in the medical record. For purposes of statistical comparisons and regression modeling, categories of race were consolidated into “white” and “nonwhite” children. Results: Of 272 subjects enrolled, 204 white and 46 nonwhite children were available for analysis. The 48-month cumulative incidence probability of death without ITx was 0.40 for nonwhite and 0.16 for white children (P < 0.001); the cumulative incidence probability of ITx was 0.07 for nonwhite versus 0.31 for white children (P = 0.003). The associations between race and outcomes remained after accounting for low birth weight, diagnosis, and being seen at a transplant center. Conclusions: Race is associated with death and receiving an ITx in a large cohort of children with IF. This study highlights the need to investigate reasons for this apparent racial disparity in outcome among children with IF.

Short-term intravenous fish oil and pediatric intestinal failure associated liver disease: 3-year follow-up on liver function and nutrition

Intravenous fish oil (FO) has changed the management of intestinal failure associated liver disease (IFALD). This report describes two IFALD patients who received FO for 5 and 10 months, respectively and reports on their 3-year follow-up.

Intravenous Fish Oil and Pediatric Intestinal Failure–Associated Liver Disease: Changes in Plasma Phytosterols, Cytokines, and Bile Acids and Erythrocyte Fatty Acids:

BACKGROUND Soybean oil (SO) emulsions are associated with intestinal failure-associated liver disease (IFALD); fish oil (FO) emulsions are used to treat IFALD. SO and FO differ with respect to their fatty acid and phytosterol content. In children with IFALD whose SO was replaced with FO, we aimed to (1) quantify changes in erythrocyte fatty acids and plasma phytosterols, cytokines, and bile acids and (2) correlate these changes with direct bilirubin (DB). DESIGN This study enrolled IFALD children who received 6 months of FO. Blood samples were collected prior to FO, and after 2 weeks and 3 and 6 months of FO. The primary outcome was 3-month vs baseline biomarker concentrations. RESULTS At study initiation, the median patient age was 3 months (interquartile range, 3-17 months), and mean ± standard deviation DB was 5.6 ± 0.7 mg/dL (n = 14). Cholestasis reversed in 79% of subjects. Eicosapentaenoic and docosahexaenoic acid was greater than baseline (P < .001, all time points). Linoleic and arachidonic acid and sitosterol and stigmasterol were less than baseline (P < .05, all time points). Three- and 6-month interleukin-8 (IL-8) and total and conjugated bile acids were less than baseline (P < .05). Baseline IL-8 was correlated with baseline DB (r = 0.71, P < .01). Early changes in stigmasterol and IL-8 were correlated with later DB changes (r = 0.68 and 0.75, P < .05). CONCLUSION Specific fat emulsion components may play a role in IFALD. Stigmasterol and IL-8 may predict FO treatment response.