Low‐Dose Parenteral Soybean Oil for the Prevention of Parenteral Nutrition–Associated Liver Disease in Neonates With Gastrointestinal Disorders

Background: Neonates with gastrointestinal disorders (GDs) are at high risk for parenteral nutrition–associated liver disease (PNALD). Soybean‐based intravenous lipid emulsions (S‐ILE) have been associated with PNALD. This study's objective was to determine if a lower dose compared with a higher dose of S‐ILE prevents cholestasis without compromising growth. Materials and Methods: This multicenter randomized controlled pilot study enrolled patients with GDs who were ≤5 days of age to a low dose (~1 g/kg/d) (LOW) or control dose of S‐ILE (~3 g/kg/d) (CON). The primary outcome was cholestasis (direct bilirubin [DB] >2 mg/dL) after the first 7 days of age. Secondary outcomes included growth, PN duration, and late‐onset sepsis. Results: Baseline characteristics were similar between the LOW (n = 20) and CON groups (n = 16). When the LOW group was compared with the CON group, there was no difference in cholestasis (30% vs 38%, P = .7) or secondary outcomes. However, mean ± SE DB rate of change over the first 8 weeks (0.07 ± 0.04 vs 0.3 ± 0.09 mg/dL/wk, P = .01) and entire study (0.008 ± 0.03 vs 0.2 ± 0.07 mg/dL/wk, P = .02) was lower in the LOW group compared with the CON group. Conclusion: In neonates with GDs who received a lower dose of S‐ILE, DB increased at a slower rate in comparison to neonates who received a higher dose of S‐ILE. Growth was comparable between the groups. This study demonstrates a need for a larger, randomized controlled trial comparing 2 different S‐ILE doses for cholestasis prevention in neonates at risk for PNALD.     

Vitamin E in New‐Generation Lipid Emulsions Protects Against Parenteral Nutrition–Associated Liver Disease in Parenteral Nutrition–Fed Preterm Pigs

Introduction: Parenteral nutrition (PN) in preterm infants leads to PN‐associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. Hypothesis: Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. Methods: We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d‐α‐tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, β‐sitosterol, campesterol, and stigmasterol). Results: Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low‐density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7‐hydroxylase and organic solute transporter–α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo ¹³C‐CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance‐associated protein 2, were higher in ILE, OV, and PS vs IL. Conclusions: α‐tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.     

Glucagon‐Like Peptide 2 Improves Cholestasis in Parenteral Nutrition–Associated Liver Disease

Background: Parenteral nutrition‐associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon‐like peptide‐2 (GLP‐2) is being advanced as therapy, the effect of GLP‐2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP‐2 administration on hepatic function in a neonatal piglet model of PNALD. Methods: Neonatal piglets (aged 2–6 days) underwent jugular venous catheterization to receive isonitrogenous, isocaloric parenteral nutrition (PN). Piglets were allocated to 2 groups: group 1 (n = 8) received saline while group 2 (n = 7) received GLP‐2 (at 11 nmol/kg/d). After 17 days, piglets underwent terminal laparotomy, and bile flow was measured. Liver specimens were analyzed histologically and with immunoperoxidase staining. Age‐matched sow‐reared control piglets (group 3, n = 8) were used for comparison. Results: Both groups 1 and 2 receiving PN developed cholestasis relative to sow‐reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared with group 1. Group 2 also had lower serum alanine aminotransferase levels, a marker of liver injury. Histologically, the liver specimens in group 1 had marked hepatocyte pigmentation, which was decreased in group 2 specimens. Conclusions: The exogenous administration of GLP‐2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP‐2 in improving PNALD in the setting of prolonged PN duration.     

Supplemental Parenteral Vitamin E Into Conventional Soybean Lipid Emulsion Does Not Prevent Parenteral Nutrition–Associated Liver Disease in Full‐Term Neonatal Piglets

Background: Parenteral nutrition–associated liver disease (PNALD) continues to cause morbidity and mortality for neonates with intestinal failure. Lipid peroxidation is one potential etiological factor. This study was designed to test if supplementing vitamin E into conventional soy‐based lipid would reduce the risk of PNALD. Methods: Sixteen piglets, aged 2–5 days and weighing 1.8–2.5 kg, were randomized to parenteral nutrition (PN) with soy lipid (SO, n = 8) or the same lipid plus α‐tocopherol, the most bioactive form of vitamin E (SO+E, n = 8). After 17 days, bile flow, liver chemistry, gene expression associated with bile acid metabolism, and bile acid composition were assessed. C‐reactive protein (CRP) and oxidative stress markers, including plasma 8‐isoprostane, were measured. All results were compared with a sow‐reared control group (CON). Results: Comparing PN‐treated groups, SO vs SO+E mean bile flow (5.91 vs 5.54 µL/g liver; P = .83), serum bile acid concentration (39.2 vs 26.6 µmol/L; P = .12), and total bilirubin (35.2 vs 26.9 µmol/L; P = .56) were not different. Gene expression related to bile acid metabolism and bile composition was not different between PN groups. There was no difference in CRP (41.8 vs 36.8 µg/mL; P = .22) or in plasma 8‐isoprostane (27.9 vs 26.1 pg/mL; P = .77). Conclusions: In term neonatal piglets, supplemental vitamin E did not prevent cholestasis. Additional vitamin E was not associated with reduced inflammation or oxidative stress. The benefit of supplementing vitamin E into conventional lipid, vs adding fish oil, to prevent early onset of PNALD requires further clarification.     

Long‐Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure–Associated Liver Disease

Background: Fish oil lipid emulsion (FOLE) and multidisciplinary care for infants with intestinal failure (IF) have been associated with reduced morbidity and mortality due to IF‐associated liver disease (IFALD). With increased survival, a greater proportion of infants with IF are now able to remain on parenteral nutrition (PN) in the long term. The purpose of this study was to examine outcomes in children with IFALD who have required long‐term PN and FOLE therapy due to chronic IF. Materials and Methods: A review of prospectively collected data was performed for children with IFALD who required at least 3 years of PN and FOLE therapy due to chronic IF. Outcomes examined include the incidence of death, transplantation, and essential fatty acid deficiency (EFAD), as well as growth parameters and the biochemical markers of liver disease. Results: Of 215 patients with IFALD treated from 2004–2015, 30 required PN and FOLE therapy for at least 3 years (median, 4.6 years). To date, no patients have died, required transplantation, or developed EFAD. Biochemical markers of liver disease normalized within the first year of therapy with no recurrent elevations in the long term. Weight‐for age and length‐for‐age z scores improved and PN dependence decreased in the first year of therapy, with a stable rate of growth in the long term. Conclusions: Children with IFALD who required long‐term PN and FOLE for chronic IF had no mortality, need for transplantation, EFAD, or recurrence of liver disease in the long term, allowing for continued intestinal rehabilitation.     

极低出生体重早产儿血清磷、骨碱性磷酸酶、25-羟基维生素D水平动态变化分析

目的 调查分析极低出生体重早产儿血清磷(P)、骨碱性磷酸酶(BALP)、25-羟基维生素D[25-(OH)D₃]水平动态变化,为临床早产儿代谢性骨病的早期预防提供指导。方法 选择入住烟台山医院新生儿科病房且符合入选标准的110例新生儿为研究对象,其中极低出生体重早产儿60例(病例组),足月产儿50例(对照组),分别于出生后1、4、12周空腹采取静脉血2 ml,测定血清P、BALP、25-(OH)D₃水平,分析骨代谢指标的变化情况。结果 病例组25-(OH)D₃水平增长速度低于对照组;两组血清P水平无明显变化。与对照组比较,病例组出生后1、4、12周血清BALP水平均显著性偏高;出生后第12周25-(OH)D₃水平的差异有统计学意义,其中病例组异常率达26.7%,对照组异常率为0。结论 极低出生体重早产儿(病例组)出生后追赶性生长过程中血清BALP、25-(OH)D₃水平与足月儿(对照组)有明显差异,提示该两项指标检测有助于极低出生体重儿代谢性骨病的早期发现及干预,其中以血清BALP指标敏感性较好。     

Pediatric Intestinal Failure–Associated Liver Disease: Challenges in Identifying Clinically Relevant Biomarkers

Background: Intestinal failure–associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug‐induced liver injury (DILI), those diagnostic criteria could potentially be used in this population. Using a preexisting database of children treated for IFALD, our aim was to determine if a similar composite biomarker could be applied to this population. Study Design: Adult DILI criteria were applied at baseline, when treatment for IFALD (ie, direct bilirubin ≥2.0 mg/dL) was initiated. Results: A total of 214 patients with IFALD treated at Boston Children’s Hospital were identified; 168 patients were eligible for analysis. Most patients analyzed were male (61%) and preterm (87%). Alkaline phosphatase (ALP) ≥2× upper limit of normal (ULN) captured the least amount of DILI (11%), while γ‐glutamyltransferase (GGT) ≥1× ULN accounted for the most (62%). Using adult DILI criteria, 60 (39%) patients with IFALD were found to have DILI. Substituting GGT ≥1× ULN for ALP ≥2× ULN improved the sensitivity, with 105 (69%) of patients meeting at least 1 criterion for DILI. Conclusion: Numerous challenges made it difficult to apply the DILI criteria to children with IFALD. Direct bilirubin, fractionated ALP, and perhaps GGT may be more suitable. Given its complex etiology and the age‐based differences due to hepatic immaturity and growth, a more suitable composite marker needs to be developed to assess IFALD in this population.     

Modified Serum ALP Values and Timing of Apparition of Knee Epiphyseal Ossification Centers in Preterm Infants with Cholestasis and Risk of Concomitant Metabolic Bone Disease of Prematurity

The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns <32 weeks. A significant correlation existed between serum ALP and direct bilirubin (DB), expressed by the regression equation: M-ALP (IU/L) = 302.1 + 96.9 (DB (mg/dL)). The ratio ALP/M-ALP > 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis.     

Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients

Background: Hypovitaminosis D exists postburn. However, evidence‐based guidelines for vitamin D repletion are unknown. This investigation examined differences between D₂ and D₃ supplementation on outcome in children with burn injuries. Methods: Fifty patients with total body surface area burn of 55.7% ± 2.6% and full‐thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7–18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D₂, D₃, or placebo was administered daily during hospitalization using a randomized, double‐blinded study design. Assay of total 25‐hydroxyvitamin D (D25), 1,25‐dihydroxyvitamin D (D1,25), 25‐hydroxyvitamin D₂ (25‐OH‐D₂), 25‐hydroxyvitamin D₃ (25‐OH‐D₃), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval. Results: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low D25 at discharge, and percent deficiency worsened by the 1‐year follow up for the placebo (75%), D₂ (56%), and D₃ (25%) groups. There were no statistical differences in PTH or clinical outcomes between treatment groups, although vitamin D supplementation demonstrated nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation. Conclusions: The high incidence of low serum D25 levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D₃ beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity.     

Fish Oil–Based Lipid Emulsions in the Treatment of Parenteral Nutrition-Associated Liver Disease: An Ongoing Positive Experience

We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children’s Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1–26). The median time to resolution of cholestasis was 40 d (range 3–158). Compared with infants with mild cholestasis (CB of 2.1–5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates.     

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.     

Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico

Abstract

This study examined the prevalence of vitamin D deficiency in mothers and infants in Tijuana, Mexico and determined the effect of a single oral dose of 50?000?IU vitamin D₃ at birth on 25-hydroxyvitamin D (25[OH]D) levels during infancy. Healthy infants were randomized to receive vitamin D₃ or placebo at birth. At birth 23% of infants were vitamin D deficient and 77% had vitamin D insufficiency (mean 25[OH]D level 18.9?ng/ml); 10% of mothers were vitamin D deficient and 61% were insufficient. Infants receiving vitamin D₃ had higher 25(OH)D levels at two months (N?=?29; 33.9 versus 24.2?ng/ml) and six months (N?=?21; 36.5 versus 27.4?ng/ml). Exclusively breastfed infants had lower 25(OH)D levels at two months (14.9 versus 33.4?ng/ml). Vitamin D deficiency is common in infants and mothers in Tijuana, Mexico. A single dose of vitamin D₃ at birth was safe and significantly increased 25(OH)D levels during infancy.     

Hormonal Relationships to Bone Mass in Elderly Spanish Men as Influenced by Dietary Calcium and Vitamin D

We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D₃) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D₃ were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D₃ levels ≥ 30 ng/mL (75 nmol/L) and a calcium intake of 800–1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL). The highest PTH levels (75.60 ± 14.16 ng/mL) were observed in the <30 ng/mL group 25-OH-Vitamin D₃ with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800–1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D₃ in the entire patient sample (r = −0.288, p = 0.019). No differences in any of the three densitometry techniques were observed between any of the age groups in the 800–1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D₃ levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters.     

Parenteral Plant Sterols Accumulate in the Liver Reflecting Their Increased Serum Levels and Portal Inflammation in Children With Intestinal Failure

Background: Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported. Materials and Methods: We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil–based lipid emulsions. Results: Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4‐fold to 5.6‐fold higher in PN‐dependent patients (P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol (r = 0.83–0.89, P = .02–.04), while serum and liver total PS levels were positively interrelated (r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN‐dependent patients. All liver PS fractions correlated positively with histologic portal inflammation (r = 0.53–0.66, P < .05), and their total concentration was significantly (P = .01) higher among patients with versus without portal inflammation. In PN‐dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels (r = 0.79–0.87, P ≤ .03). Conclusion: Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.     

不同年龄段小儿血清骨碱性磷酸酶水平的测定

目的:测定不同年龄段骨碱性磷酸酶的水平,并探讨其变化规律。方法:在儿科门诊查体或因某些感染性疾病如上呼吸道感染、心肌炎、肺炎等原因住院的166例患儿和高中、初中健康检体的学生154例作为研究对象。按照传统分组分别将男女研究对象分为6组,采用ELISA法测定骨碱性磷酸酶及总碱性磷酸酶。结果:在生长发育过程的不同阶段,男孩血清骨碱性磷酸酶的水平不同,6个年龄段分组的血清骨碱性磷酸酶水平有差别(F=6.722,P<0.01)。女孩6个年龄段分组之间的血清骨碱性磷酸酶水平无差别(F=2.089,P=0.071>0.05)。结论:小儿血清骨碱性磷酸酶的浓度变化与年龄有关,监测血清骨碱性磷酸酶的水平变化可以准确地判断小儿各阶段生长发育状况。     

Treatment of Parenteral Nutrition-Associated Liver Disease: The Role of Lipid Emulsions

Parenteral nutrition is a life-saving therapy for infants with intestinal failure. However, long-term parenteral nutrition carries the risk of progressive liver disease. Substantial data has implicated components of parenteral soybean oil in the pathogenesis of parenteral nutrition-associated liver disease (PNALD). Elevated serum concentrations of phytosterols, an abundance of omega-6 polyunsaturated fatty acids, and a relative paucity of α-tocopherol have been associated with the risk of cholestasis and hepatic injury observed in PNALD. Currently available treatment strategies include the reduction of the dose of administered parenteral soybean oil and/or the replacement of parenteral soybean oil with alternative parenteral lipid emulsions. The purpose of this review is to provide an overview of the pathogenetic mechanisms associated with the development of PNALD and the data evaluating currently available treatment strategies.     

Vitamin D Deficiency in Children With Intestinal Failure Receiving Home Parenteral Nutrition

Background: Vitamin D plays important roles in both skeletal and nonskeletal health. Limited data suggest that patients with intestinal failure (IF) receiving home parenteral nutrition (PN) are at risk for vitamin D deficiency due to inadequate oral intake, poor absorption, and chronic illness. The purpose of this study was to document vitamin D status in pediatric patients with IF receiving home PN. Materials and Methods: We performed a 2‐year retrospective review of children with IF followed at our center who had been on home PN for ≥6 months and had ≥1 serum 25‐hydroxyvitamin D (25‐OHD) level checked as part of routine clinical care. Patients were then categorized as deficient (<20 ng/mL), insufficient (20–29 ng/mL), or normal (≥30 ng/mL) based on their lowest vitamin D level. Demographic data and clinical characteristics were also assessed. Results: Eleven of 27 children (41%) had ≥1 insufficient 25‐OHD level, including one child with vitamin D deficiency. Diagnosis of short bowel syndrome (compared with dysmotility or malabsorption syndromes) was associated with decreased likelihood of suboptimal vitamin D status, with an odds ratio of 0.12 (95% confidence interval, 0.02–0.8, P = .028). Osteopenia was noted in 59% of the cohort. There was a trend toward higher risk for osteopenia in patients with low 25‐OHD levels compared with those with normal 25‐OHD levels (82% vs 44%, P = .109). Conclusion: Suboptimal 25‐OHD levels are common in children with IF on home PN. This emphasizes the critical importance of routine surveillance of serum vitamin D levels and consideration of enteral supplementation when indicated.     

A.S.P.E.N. Clinical Guidelines

Background: Children with severe intestinal failure and prolonged dependence on parenteral nutrition are susceptible to the development of parenteral nutrition–associated liver disease (PNALD). The purpose of this clinical guideline is to develop recommendations for the care of children with PN‐dependent intestinal failure that have the potential to prevent PNALD or improve its treatment. Method: A systematic review of the best available evidence to answer a series of questions regarding clinical management of children with intestinal failure receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. Questions: (1) Is ethanol lock effective in preventing bloodstream infection and catheter removal in children at risk of PNALD? (2) What fat emulsion strategies can be used in pediatric patients with intestinal failure to reduce the risk of or treat PNALD? (3) Can enteral ursodeoxycholic acid improve the treatment of PNALD in pediatric patients with intestinal failure? (4) Are PNALD outcomes improved when patients are managed by a multidisciplinary intestinal rehabilitation team?     

An evaluation of the model for end-stage liver disease and serum C-reactive protein as prognostic markers in intestinal failure patients on parenteral nutrition

Background: Intestinal failure (IF) patients require parenteral nutrition (PN) to avoid malnutrition and death. However, they face complications of recurrent sepsis and liver failure. By the time liver failure is discovered, it is often too late for intervention and prognosis on the waiting list is grim. The Model for End‐Stage Liver Disease (MELD) has traditionally been used to predict mortality in patients with liver failure but has never been analyzed in IF patients who are at risk for liver complications. C‐reactive protein (CRP) is an acute inflammatory marker that has been shown to reflect disease progression in nonalcoholic steatohepatitis, a disease that in many ways resembles PN‐associated liver disease. MELD and CRP are promising clinical markers of disease progression in IF patients on PN. Methods: The authors performed a retrospective, case‐control study to compare levels of MELD and CRP within the entire population of 133 adult patients referred to Northwestern Memorial Hospital for IF from 1999 to 2006. Results: Elevated MELD score is strongly predictive of increased mortality over the subsequent 6 months. Elevated CRP is strongly predictive over a smaller 3‐month window. One‐year mortality was significantly greater in patients who have either elevated MELD scores or serum CRP levels. Conclusions: In this study, the authors evaluated for the first time use of MELD and serum CRP as predictive markers of mortality in IF patients. Both seem to be promising clinical tools to identify which patients are at highest risk for complication.