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Background Infants with intestinal failure (IF) and IF-associated liver disease (IFALD) are at risk for poor somatic growth because of increased metabolic demands, inadequate intake, intestinal malabsorption, chronic liver disease and other comorbidities. There are limited data on the nutritional adequacy of intravenous fish oil lipid emulsion (FOLE) compared with standard soybean oil lipid emulsion (SOLE) in the setting of intestinal failure. Aims To describe growth patterns in a large cohort of infants with IFALD treated with FOLE. Methods We compared growth data from infants enrolled in a single-center, prospective FOLE study to published norms, as well as to a multicenter, historical cohort of infants with IF treated with SOLE. Results One hundred thirty-eight infants with IFALD were treated with FOLE and 108 with SOLE. Compared with normative growth curves from WHO and published preterm data, infants in both groups from 6 to 11 months postmenstrual age exhibited declines in mean weight- and length-for-age z scores. At 24 months postmenstrual age compared with WHO growth data, infants treated with FOLE had a mean (95% confidence interval [CI]) weight-for-age z-score of 0.13 (-0.18 to 0.45) and length-for-age z-score of 0.07 (-0.33 to 0.47). In comparison, at 24 months postmenstrual age, infants treated with SOLE had a mean weight for age z-score of -0.93 (-1.20 to -0.67) and mean length for age z-score of -2.33 (-2.75 to -1.91). Independent predictors of higher weight, length and head circumference z-scores included older postmenstrual age at baseline, fewer central line-associated blood stream infections, resolution of cholestasis, type of intravenous fat emulsion (FOLE vs SOLE) and female sex. Conclusions Infants with IFALD treated with FOLE showed comparable somatic growth to those treated with SOLE in early infancy, and improved somatic growth up to 24 months of age, supporting its wider use in this patient population.

BACKGROUND: Vitamin K is a fat-soluble compound that plays important roles in coagulation. In children with intestinal failure associated liver disease (IFALD), the disrupted enterohepatic circulation can lead to intestinal loss of vitamin K. Fish oil-based lipid emulsion (FOLE) has proven effective in treating IFALD. As biliary excretion is restored during cholestasis reversal, the accelerated vitamin K loss can pose a risk for deficiency. METHODS: Ten neonates with IFALD receiving FOLE monotherapy were prospectively enrolled in the study from 2016 to 2018. In addition to weekly measurements of international normalized ratio (INR) and direct bilirubin (DB), ostomy output was collected for determination of fecal concentrations of phylloquinone (PK) with mass spectrometry. Trends of DB, INR, and fecal PK concentrations were summarized with locally estimated scatterplot smoothing. RESULTS: The median time (interquartile range) from FOLE initiation to cholestasis reversal was 59 (19–78) days. During cholestasis reversal, INR remained relatively unchanged while the mean (95% confidence interval; CI) daily fecal excretion of PK increased from 25.1 (5.0, 158.5) ng at the time of FOLE initiation to 158.5 (31.6, 1000.0) ng at complete reversal. Examination of individual trends in fecal PK excretion and INR also revealed little correlation between the two measurements (r = −0.10; P=0.50). CONCLUSION: Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone as it is a poor indicator of vitamin K status.

Intestinal failure-associated liver disease (IFALD) can be treated with parenteral fish oil (FO) monotherapy, but practitioners have raised concerns about a potential bleeding risk. This study aims to describe the incidence of clinically significant post-procedural bleeding (CSPPB) in children receiving FO monotherapy.A retrospective chart review was performed on patients at our institution treated with intravenous FO for IFALD. CSPPB was defined as bleeding leading to re-operation, transfer to the intensive care unit, re-admission, or death, up to one month after any invasive procedure.From 244 patients reviewed, 183 underwent ≥1 invasive procedure(s) (n = 732). Five (0.68%, 95% CI 0.22-1.59%) procedures resulted in CSPPB. FO therapy was never interrupted. No deaths due to bleeding occurred.Findings suggest that FO therapy is safe, with a CSPPB risk no greater than that reported in the general population. O3FA should not be held in preparation for procedures or in the event of bleeding.

There are few evidence-based guidelines to inform optimal design of complex clinical trials, such as those assessing the safety and efficacy of intravenous drugs administered daily with infusion times over many hours per day and treatment durations that may span years. This study is a retrospective review of inpatient administration deviation reports for an investigational drug that is administered daily with infusion times of 8–24 h, and variable treatment durations for each patient. We report study design modifications made in 2007–2008 aimed at minimizing deviations from an investigational drug infusion protocol approved by an institutional review board and the United States Food and Drug Administration. Modifications were specifically aimed at minimizing errors of infusion rate, incorrect dose, incorrect patient, or wrong drug administered. We found that the rate of these types of administration errors of the study drug was significantly decreased following adoption of the specific study design changes. This report provides guidance in the design of clinical trials testing the safety and efficacy of study drugs administered via intravenous infusion in an inpatient setting so as to minimize drug administration protocol deviations and optimize patient safety.

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, requir...

While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line-associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures.A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed.Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C-reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours.Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.

BACKGROUND: Home parenteral nutrition (HPN) is a life-sustaining therapy for short bowel syndrome (SBS) and other severe digestive diseases, but complications are common. We aimed to evaluate an intensive pre-discharge HPN hands-on training course to reduce complications in children with SBS, including hospital readmissions. METHODS: We conducted a prospective, non-randomized controlled research study between April 1, 2014 and April 30, 2017. Eligible subjects were children age

Elevated serum alkaline phosphatase (ALP) in infants with intestinal failure (IF) can be due to parenteral nutrition-associated liver disease (PNALD) or metabolic bone disease (MBD). The purpose of the study was to determine the utility of serum ALP in the diagnostic criteria for PNALD by measuring tissue-specific levels in infants with IF and PNALD.A retrospective review of patient data for 15 infants diagnosed with PNALD between December 2012 and August 2013 was performed. PNALD was defined as the presence of 2 consecutive direct bilirubin (DB) levels2 mg/dL. Fractionated serum alkaline phosphatase was measured in each patient, while the DB was2 mg/dL. Parathyroid hormone (PTH), vitamin D3, calcium, and phosphate levels were recorded where available.In 15 infants with PNALD, elevation in total ALP was due to marked elevations in bone-specific ALP. The median liver-specific ALP remained within the normal range. PTH, vitamin D3, calcium, and phosphate levels were within normal limits.While elevated ALP can reflect biliary stasis, the ALP elevation observed in infants with IF and PNALD is predominantly of bone rather than hepatic origin. An elevated unfractionated ALP in infants with PNALD should therefore raise suspicion of underlying bone disease, rather than being attributed to liver disease alone.

Objective. To assess the safety and efficacy of a fish oil–based intravenous fat emulsion (FIFE) in reducing the incidence of cholestasis in neonates compared with the traditional soybean oil–based intravenous fat emulsion (SIFE). Methods. A double-blind randomized controlled trial was conducted. Nineteen neonates were enrolled (10 SIFE; 9 FIFE). Nutrition assessments and laboratory studies were serially obtained for the duration of PN support or until 6 months’ corrected gestational age. Neurodevelopmental outcomes were assessed at 6 and 24 months’ corrected age. Results. There were no differences between groups in demographic characteristics, with an overall median age of 2 days, gestational age of 36 weeks, and birth weight of 2410 g. There were no differences between groups in baseline laboratory values other than alkaline phosphatase (lower in the FIFE group) or in the duration of parenteral nutrition (PN), amount of enteral intake, or the number of operative procedures. The incidence of cholestasis ...

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.Adult DILI criteria were applied at baseline, when treatment for IFALD (ie, direct bilirubin ≥2.0 mg/dL) was initiated.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.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.

Background Adhesions represent a major problem after abdominal and pelvic procedures. The purpose of the present study was to determine the effect of sunitinib (Sutent, SU11248), a Food and Drug Administration-approved receptor tyrosine kinase inhibitor, on recurrent pelvic adhesion formation after pelvic adhesiolysis in a rabbit model. Materials and methods A total of 20 New Zealand white rabbits underwent a uterine abrasion procedure, followed by an adhesiolysis procedure 4 weeks later. Before adhesiolysis, the rabbits were randomized to sunitinib at 10 mg/kg/d or placebo. These were administered as 1 dose preoperatively followed by 10 doses postoperatively. The rabbits were killed 30 d after the adhesiolysis procedure. At death, the adhesions were scored, and a total adhesion score (presented as the median and interquartile range [IQR]) was calculated according to the percentage of uterine involvement and the tenacity of the adhesions. Results All the rabbits survived the operative procedures without complications. The sunitinib-treated rabbits (n = 10) had a significantly lower uterine involvement score (median 2.0, IQR 1.0–3.0) than the placebo-treated rabbits (median 4.0, IQR 3.0–4.0; P = 0.02). The sunitinib-treated rabbits also had median tenacity score of 3.0 (IQR 3.0–4.0) compared with a median of 4.0 (IQR 4.0–4.0; P = 0.04) in the placebo-treated rabbits (n = 10). The median total score in the sunitinib-treated rabbits was 5.0 (IQR 4.0–6.25) compared with 8.0 (IQR 6.75, 8.0) in the placebo-treated rabbits (P = 0.01). Conclusions Sunitinib treatment might be an efficacious strategy to reduce recurrent adhesion formation after pelvic procedures.

Purpose The aim of this study was to determine the incidence of cholestasis and the correlation between cholestasis and weight-for-age z scores in parenteral nutrition–dependent neonates with gastroschisis. Methods A single-center retrospective review of 59 infants born with gastroschisis from January 2000 to June 2007 was conducted. Demographic and clinical data were collected and analyzed. Subjects were divided into cholestatic and noncholestatic groups. Statistical analyses included the Student t test, Wilcoxon rank sum test, Fisher exact test, and a general linear model. Results Fifty-nine neonates with gastroschisis were identified, and 16 (28%) of 58 patients developed cholestasis. Younger gestational age and cholestasis were found to be independently associated with weight-for-age z score in 30 of 58 patients with available long-term follow-up data. Conclusions Parenteral nutrition–dependent neonates with gastroschisis remain at considerable risk for the development of cholestasis. Both gestational age and cholestasis were found to be independent risk factors, predisposing these neonates to poor postnatal growth.

Background: Necrotizing enterocolitis (NEC) is one of the most devastating diseases in the neonatal population, with extremely low birth weight and extremely preterm infants at greatest risk. Method: A systematic review of the best available evidence to answer a series of questions regarding nutrition support of neonates at risk of NEC was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the A.S.P.E.N. Board of Directors. Results/Conclusions: (1) When and how should feeds be started in infants at high risk for NEC? We suggest that minimal enteral nutrition be initiated within the first 2 days of life and advanced by 30 mL/kg/d in infants ≥1000g. (Weak) (2) Does the provision of mother's milk reduce the risk of developing NEC? We suggest the exclusive use of mother's milk rather than bovine-based products or formula in infants at risk for NEC. (Weak) (3) Do probiotics reduce the risk of developing NEC? There are insufficient data to recommend the use of probiotics in infants at risk for NEC. (Further research needed.) (4) Do nutrients either prevent or predispose to the development of NEC? We do not recommend glutamine supplementation for infants at risk for NEC (Strong). There is insufficient evidence to recommend arginine and/or long chain polyunsaturated fatty acid supplementation for infants at risk for NEC. (Further research needed.) (5) When should feeds be reintroduced to infants with NEC? There are insufficient data to make a recommendation regarding time to reintroduce feedings to infants after NEC. (Further research needed.) (JPEN J Parenter Enteral Nutr. 2012;36:506-523)

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.

Purpose This study compares postoperative markers of liver injury in patients receiving intravenous fish oil (IFO) with parenteral nutrition (PN)–associated cholestasis (PNAC) to patients with resolved PNAC. Methods A retrospective review of all cholestatic-IFO patients undergoing abdominal laparotomy between March 1, 2007, and July 1, 2009, led to inclusion of 23 patients who collectively underwent 27 abdominal operations (13 pre-PNAC resolution and 14 post-PNAC resolution). Direct bilirubin (DB), total bilirubin, and alanine aminotransferase levels were examined over time in relation to operations. The time to resume presurgical trend of decreasing DB was calculated. Results Sixty-nine percent (9/13) of pre-PNAC resolution procedures were associated with postoperative increase in DB compared with 7% (1/14) of post-PNAC resolution procedures associated with a recurrence of cholestasis ( P = .02; odds ratio, 29.3; 95% confidence interval, 2.79-306.8). The median time to return to the preoperative downward trend of DB was 21 days. Conclusions Operations before PNAC resolution may be associated with an increased postoperative DB, possibly reflecting an exacerbation of liver injury. Operations post-PNAC resolution on IFO had a comparatively low incidence of postoperative cholestasis recurrence. Excepting clinical indication otherwise, it may be advisable to delay surgical intervention in the setting of PNAC in certain cases.

To assess forced expiratory tracheal collapsibility in healthy volunteers by using multidetector computed tomography and to compare the results with the current diagnostic criterion for tracheomalacia.An institutional review board approved this HIPAA-compliant study. After informed consent was obtained, 51 healthy volunteers (age range, 25-75 years) with normal spirometry results and no history of smoking or risk factors for tracheomalacia were prospectively studied. Volunteers were imaged with a 64-detector row scanner, with spirometric monitoring at total lung capacity and during forced exhalation, with 40 mAs, 120 kVp, and 0.625-mm detector collimation. Cross-sectional area and sagittal and coronal diameters of the trachea were measured 1 cm above the aortic arch and 1 cm above the carina. The percentage of expiratory collapse, the reduction in sagittal and coronal diameters, and the number of participants exceeding the current diagnostic criterion (50% expiratory reduction in cross-sectional area) for tracheomalacia were calculated.The final study population included 25 men and 26 women (mean age, 50 years). The mean percentage of expiratory reduction in tracheal lumen cross-sectional area was 54.34% +/- 18.6 (standard deviation) in the upper trachea and 56.14% +/- 19.3 in the lower trachea. Forty (78%) participants exceeded the current diagnostic criterion for tracheomalacia in the upper and/or lower trachea. Decreases in cross-sectional area of the upper and lower trachea correlated well with decreases in sagittal (r = 0.807 and 0.688, respectively) and coronal (r = 0.779 and 0.751, respectively) diameters (P.001 for each correlation).Healthy volunteers demonstrate a wide range of forced expiratory tracheal collapse, frequently exceeding the current diagnostic criterion for tracheomalacia.

Objectives Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. Methods The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. Results Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. Conclusions Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.

Importance The introduction of hepatoprotective strategies and multidisciplinary management has significantly improved the outcome of neonates with short bowel syndrome (SBS) who require parenteral nutrition (PN). Objective To determine the probability of weaning from PN based on intestinal length in neonates with SBS amidst the new era of hepatoprotective strategies and multidisciplinary management. Design, Setting, and Participants Retrospective medical record review at a single-center academic institution. Neonates with no more than 100 cm of small intestine at a corrected gestational age of no more than 30 days who were diagnosed with a surgical gastrointestinal disease and PN dependent for at least 2 weeks were included. Data were collected from January 1, 2004, through June 1, 2012. Exposure Neonates with SBS requiring PN. Main Outcomes and Measures The probability of wean from PN without reinitiation for at least 1 year, as determined by logistic regression. Predictors of wean were evaluated using exact conditional logistic regression. Predictors of time to wean were determined by Cox proportional hazards regression. Results Sixty-three patients with a median (25th percentile, 75th percentile [interquartile range (IQR)]) gestational age of 31 (27, 35) weeks, birth weight of 1423 (895, 2445) g, small intestinal length of 41.0 (24.0, 65.0) cm, and predicted length of 29.0% (17.1%, 45.5%) underwent analysis. Fifty-one patients (81%) received a fish oil–based lipid emulsion (1 g/kg/d), 40 (63%) were weaned, 11 (17%) remained PN dependent, 4 (6%) underwent transplant, and 8 (13%) died while on PN. Excluding patients who underwent transplant or died, the median (IQR) small intestinal length was 55.0 (28.0, 75.0) cm in weaned and 26.0 (14.0, 41.0) cm in PN-dependent patients ( P = .006), with 40 of 51 (78%) weaned by study end. The cumulative probability of wean for patients with at least 50 cm of small intestine was 88% after 12 and 96% after 24 months. Patients with less than 50 cm of small intestine had a cumulative probability of wean of 23% after 12, 38% after 24, and 71% after 57 months. Small intestinal length was found to be the primary predictor of wean. Notable predictors of time to wean included the amount of small intestine remaining (hazard ratio, 1.94 [95% CI, 1.45-2.58] per 20 cm of intestine; P P = .001), and intestinal lengthening procedure (0.19 [0.04-0.84]; P = .03). Conclusions and Relevance The majority of patients will wean from PN despite short intestinal length, likely as a result of new management strategies combined with a multidisciplinary team approach.

OBJECTIVE To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy. BACKGROUND Historically, cirrhosis from PNALD resulted in end-stage liver disease, often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to end-stage liver disease. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. METHODS Prospectively collected data were reviewed for children with cirrhosis because of PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. RESULTS Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (P < 0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from end-stage liver disease. Pediatric End-Stage Liver Disease scores decreased from 16 ± 4.6 to -1.2 ± 4.6, 12 months after resolution of cholestasis (P < 0.001). In children who remained PN-dependent, the Pediatric End-Stage Liver Disease score remained normal throughout the follow-up period. CONCLUSIONS Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent.

Background: Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. Method: A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation 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) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk? (JPEN J Parenter Enteral Nutr. 2013;37:570-598)

One of the most common and severe complications of long-term parenteral nutrition (PN) is PN-associated cholestasis. The soybean oil-based lipid emulsion administered with PN has been associated with cholestasis, leading to an interest in lipid reduction strategies. The purpose of this study was to determine whether the provision of a soybean oil-based lipid emulsion at 1 g/kg/d compared with 2-3 g/kg/d is associated with a reduced incidence of cholestasis.Retrospective review of neonates admitted between 2007 and 2011 with a gastrointestinal condition necessitating ≥ 21 days of PN support. Neonates were divided into 2 groups based on the intravenous lipid emulsion dose: 1-g group (1 g/kg/d) and 2- to 3-g group (2-3 g/kg/d). The primary outcome measure was the incidence of cholestasis.Sixty-one patients met inclusion criteria (n = 29, 1-g group; n = 32, 2- to 3-g group). The 2 groups did not differ in any baseline characteristics other than associated comorbidities that were more common in the 2- to 3-g group. The duration of PN, the number of operative procedures and bloodstream infections, and enteral nutrition (EN) were similar between groups. The incidence of cholestasis was not different between groups (51.7%, 1-g group; 43.8%, 2- to 3-g group; P = .61), and there was no difference between groups in the time to cholestasis (32.6 ± 24.1 days, 1-g group; 27.7 ± 10.6 days, 2- to 3-g group; P = .48). Overall, 44.8% of patients with cholestasis were transitioned to full EN, and 55.2% were transitioned to a fish oil-based lipid emulsion after which the direct bilirubin normalized in all patients.Lipid reduction to 1 g/kg/d does not prevent or delay the onset of cholestasis in neonates.

Background: Total parenteral nutrition (PN), including fat administered as a soybean oil–based lipid emulsion (SOLE), is a life-saving therapy but may be complicated by PN-induced cholestasis and dyslipidemia. A fish-oil–based lipid emulsion (FOLE) as a component of PN can reverse PN-cholestasis and has been shown to improve lipid profiles. Objective: The objective was to describe changes in the fatty acid and lipid profiles of children with PN-cholestasis who were treated with a FOLE. Design: Lipid and fatty acid profiles of 79 pediatric patients who developed PN-cholestasis while receiving standard PN with a SOLE were examined before and after the switch to a FOLE. All patients received PN with the FOLE at a dose of 1 g kg 21 d 21 for 1 mo. Results: The median (interquartile range) age at the start of the FOLE treatment was 91 (56–188) d. After a median (interquartile range) of 18.3 (9.4–41.4) wk of receiving the FOLE, the subjects’ median total and direct bilirubin improved from 7.9 and 5.4 mg/dL to 0.5 and 0.2 mg/dL, respectively (P , 0.0001). Serum triglyceride, total cholesterol, LDL, and VLDL concentrations significantly decreased by 51.7%, 17.4%, 23.7%, and 47.9%, respectively. Conclusions: The switch from a SOLE to a FOLE in PN-dependent children with cholestasis and dyslipidemia was associated with a dramatic improvement in serum triglyceride and VLDL concentrations, a significant increase in serum omega-3 (n23) fatty acids (EPA and DHA), and a decrease in serum omega-6 fatty acids (arachidonic acid). A FOLE may be the preferred lipid emulsion in patients with PN-cholestasis, dyslipidemia, or both. This trial is registered at clinicaltrials.gov as NCT00910104. Am J Clin Nutr doi: 10.3945/ajcn.110.008557.