Outcomes in preterm infants who received a lipid emulsion with fish oil: An observational study.

BACKGROUND: 100% soybean oil emulsions (SO100) are associated with poor docosahexaenoic acid (DHA) and arachidonic acid (ARA) status in extremely low birth weight (ELBW) infants. A multi-oil emulsion with 15% fish oil (FO15) contains more DHA and ARA than SO100. This study compares clinical outcomes, namely growth and fatty acids, in ELBW infants who received S0100 or FO15. METHODS: This observational study included ELBW infants born between 2014 and 2019 who received SO100 or FO15 for >7 days. Gas chromatography/mass spectrometry was used to measure erythrocyte fatty acids. RESULTS: The mean ± SD gestational age was 27 ± 3 and 26 ± 2 weeks for SO100 (n = 43) and FO15 (n = 43), respectively (P = 0.2). DHA (-0.3 ± 0.10% per week, P = 0.026, for FO15 vs -0.2 ± 0.05% per week, P < 0.001, for SO100) and ARA (-0.8 ± 0.21% per week for FO15 vs -0.9 ± 0.17% per week for SO100; P < 0.001 for both) declined in both groups with no difference between groups (P interaction > 0.7 for both). After controlling for days to reach full feeds, the mean difference in weight z score trajectories was similar (Est = -0.08; 95% CI, -0.82 to 0.04; P = 0.2), and SO100 was associated with a nonsignificant increased odds for cholestasis (odds ratio, 3.1; 95% CI, 0.96-10.2; P = 0.059). There was no difference in other clinical comorbidities. CONCLUSIONS: In comparison with ELBW infants who received SO100, infants who received FO15 still demonstrated a decline in DHA and ARA. Growth and other clinical outcomes were unchanged.

Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events.

OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study.

OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil.

BACKGROUND: There is evidence that microRNA (MIR) 122 is a biomarker for various liver diseases in adults and children. To date, MIR122 has not been explored in children with intestinal failure-associated liver disease (IFALD, or hyperbilirubinemia associated with prolonged parenteral nutrition). OBJECTIVES: This study's purpose was to investigate changes in plasma miR-122, correlate miR-122 with serum liver function tests and enzymes, and investigate changes in whole blood transcripts including miR-122 targets in a group of children with IFALD who received pure intravenous fish oil (FO) as a treatment for cholestasis. METHODS: This was a prospective, observational study that enrolled children with IFALD who received intravenous FO (1 g/kg/d) and whose cholestasis resolved with FO. Plasma miR-122 was measured using reverse transcription-quantitative real-time PCR, and whole blood miR-122 targets were quantified using RNA sequencing. RESULTS: Fourteen subjects with median age 6 mo (IQR: 3-65 mo) were enrolled. RNA sequence data were available for 4 subjects. When compared with the start of FO, median miR-122 concentrations at 6 mo of FO therapy decreased [1.0 (IQR: 1.0-1.0) compared with 0.04 (IQR: 0.01-0.6), P = 0.009]. At the start of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.038). At ∼3 mo of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.045). Reactive oxygen species, heme metabolism, coagulation, adipogenesis, IL-6-Janus kinase-signal transducer and activator of transcription (JAK-STAT) 3, IL-2-STAT5, transforming growth factor-ß, TNF-α, inflammatory response, mammalian target of rapamycin gene families (normalized enrichment scores < -1.4), and miR-122 target genes were significantly downregulated with FO. CONCLUSIONS: In this small cohort of young children with IFALD, miR-122 decreased with FO therapy and correlated with conjugated bilirubin. Key pathways involving oxidation, inflammation, cellular differentiation, and nutrient regulation were downregulated. Data from this study provide information about IFALD and FO. This trial was registered at www.clinicaltrials.gov as NCT00969332.

Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease.

OBJECTIVE: To compare growth in children with intestinal failure-associated liver disease (IFALD) who received a fish oil intravenous lipid emulsion (FOLE) to those who received a soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: This multisite, retrospective study pair-matched FOLE (n = 82) to SOLE recipients (n = 41) using baseline serum direct bilirubin levels and postmenstrual age. Study subjects received open-label FOLE (1 g/kg/day) until IFALD resolved or parenteral nutrition was stopped. Historical control subjects received SOLE (up to 3 g/kg/day). Growth measures (changes in body weight, height/length, and head circumference), prealbumin, triglycerides, and glucose were compared between groups over time using the Wilcoxon rank-sum test. RESULTS: Although changes in all of the growth measures were similar for both groups (P > .05), FOLE recipients demonstrated an overall improved growth trajectory. After 28 weeks, FOLE recipients had a mean body weight within a z score range of -1 to 1 indicating age-appropriate growth. FOLE recipients consistently had higher prealbumin, lower triglyceride, and more normal glucose concentrations over time compared with SOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had similar growth and fewer metabolic abnormalities compared with those who received SOLE. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

Use of Fish Oil Intravenous Lipid Emulsions as Monotherapy in the Pediatric Intestinal Failure Patient: Beyond the Package Insert.

In July 2018, an intravenous lipid emulsion (ILE) composed of 100% fish oil (Omegaven, Fresenius Kabi, Bad Homburg, Germany) received Food and Drug Administration (FDA) approval as a source of fatty acids and calories for infants and children with parenteral nutrition-associated cholestasis. This soy-free fat source is rich in ω-3 fatty acids and α-tocopherol and contains few phytosterols. In comparison to conventional soybean oil ILE, this emulsion appears to be less hepatotoxic. The purpose of this paper is to guide the practitioner on the use of this alternative fat source in clinical practice and augment the material contained in the current package insert. This paper addresses various topics including the identification of which patients would benefit from fish oil ILE, dosing, administration, monitoring, potential adverse effects, and management strategies for fish oil ILE.

Adherence to and outcomes of a University-Consortium gastroschisis pathway.

BACKGROUND: Our multi-institutional university consortium implemented a gastroschisis pathway in 2015 to standardize and improve care by promoting avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics/narcotics within 48 h of closure, and early initiation/advancement of feeds. METHODS: Adherence to the gastroschisis pathway was prospectively monitored. Outcomes for the contemporary cohort (2015-2018) were compared with a historical cohort (2007-2012). RESULTS: Good adherence to the pathway was observed for 70 cases of inborn uncomplicated gastroschisis. The contemporary cohort had significantly lower median mechanical ventilator days (2 versus 5; p < 0.01) and antibiotic days (5.5 versus 9; p < 0.01) as well as earlier days to initiation of feeds (12 versus 15; p < 0.01). However, no differences were observed in length of stay (28 versus 29 days; p = 0.70). A skin closure technique was performed in 66% of the patients, of which 46% were performed at bedside without intubation, the assistance of an operating-room team, or general anesthesia. CONCLUSION: In this study, adherence to a clinical pathway for gastroschisis across different facilities was feasible and led to reduction in exposure to mechanical ventilation and antibiotics. The adoption of a bedside skin closure technique appears to facilitate compliance with the pathway. LEVEL OF EVIDENCE: Level II/III TYPE OF STUDY: Prospective comparative study with historical cohort.

Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease.

BACKGROUND: Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ω-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. METHODS: Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. RESULTS: Subjects (n = 17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P < 0.001 for all). Triene-tetraene ratios remained unchanged (P = 1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P < 0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P = 0.08). CONCLUSION: In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.

Long-Term Outcomes in Children With Intestinal Failure-Associated Liver Disease Treated With 6 Months of Intravenous Fish Oil Followed by Resumption of Intravenous Soybean Oil.

BACKGROUND: Intravenous soybean oil (SO) is a commonly used lipid emulsion for children with intestinal failure (IF); however, it is associated with IF-associated liver disease (IFALD). Studies have demonstrated that intravenous fish oil (FO) is an effective treatment for IFALD. However, there is a lack of long-term data on children who stop FO and resume SO. This study's objective was to investigate our institution's outcomes for children with IFALD treated with 6 months of FO and who then restarted SO. METHODS: Inclusion criteria for FO included children with IFALD. Parenteral nutrition (PN)-dependent children resumed SO after FO and were prospectively followed for 4.5 years or until death, transplant, or PN discontinuation. The primary outcome was the cumulative incidence rate (CIR) for cholestasis after FO. RESULTS: Forty-eight subjects received FO, and conjugated bilirubin decreased over time (-0.22 mg/dL/week; 95% confidence interval [CI]: -0.25, -0.19; P < .001). The CIR for cholestasis resolution after 6 months of FO was 71% (95% CI: 54%, 82%). Twenty-seven subjects resumed SO and were followed for a median of 16 months (range 3-51 months). While the CIR for enteral autonomy after 3 years of follow-up was 40% (95% CI: 17%, 26%), the CIR for cholestasis and transplant was 26% (95% CI: 8%, 47%) and 6% (95% CI: 0.3%, 25%), respectively. CONCLUSION: In this study, FO effectively treated cholestasis, and SO resumption was associated with cholestasis redevelopment in nearly one-fourth of subjects. Long-term FO may be warranted to prevent end-stage liver disease.

Early dietary restriction in rats alters skeletal muscle tuberous sclerosis complex, ribosomal s6 and mitogen-activated protein kinase.

Intrauterine growth restriction is linked to decreased lean body mass and insulin resistance. The mammalian target of rapamycin (mTOR) regulates muscle mass and glucose metabolism; however, little is known about maternal dietary restriction and skeletal muscle mTOR in offspring. We hypothesized that early dietary restriction would decrease skeletal muscle mass and mTOR in the suckling rat. To test this hypothesis, ab libitum access to food or dietary restriction during gestation followed by postnatal cross-fostering to a dietary-restricted or ad libitum-fed rat dam during lactation generated 4 groups: control (CON), intrauterine dietary restricted (IUDR), postnatal dietary restricted (PNDR), and IUDR+PNDR (IPDR). At day 21, when compared to CON, the IUDR group demonstrated "catchup" growth, but no changes were observed in the mTOR pathway. Despite having less muscle mass than CON and IUDR (P < .001), in IPDR and PNDR rats mTOR remained unchanged. IPDR and PNDR (p)-tuberous sclerosis complex 2 was less than the IUDR group (P < .05). Downstream, IPDR's and PNDR's phosphorylated (p)-ribosomal s6 (rs6)/rs6 was less than that of CON (P < .05). However, male IPDR's and PNDR's p-mitogen activated protein kinase MAPK/MAPK was greater than CON (P < .05) without a change in p90 ribosomal s6 kinase (p90RSK). In contrast, in females, MAPK was unchanged, but IPDR p-p90RSK/p90RSK was less than CON (P = .01). In conclusion, IPDR and PNDR reduced skeletal muscle mass but did not decrease mTOR. In IPDR and PNDR, a reduction in tuberous sclerosis complex 2 may explain why mTOR was unchanged, whereas, in males, an increase in MAPK with a decrease in rs6 may suggest a block in MAPK signaling.

Two-Year Neurodevelopment and Growth Outcomes for Preterm Neonates Who Received Low-Dose Intravenous Soybean Oil.

BACKGROUND: In some studies, the dose of intravenous soybean oil (SO) has been associated with a decreased incidence of intestinal failure-associated liver disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains unknown. This study investigated the impact of SO dose on ND and growth over the first 2 years of age in preterm neonates. MATERIALS AND METHODS: This is a single-site prospective follow-up study. Neonates with a gestational age ≤29 weeks were randomized to low-dose (LOW) or standard-dose (CON) SO. Bayley Scales of Infant Development III and anthropometric measurements were collected at approximately 6, 12, and 24 months corrected gestational age. RESULTS: Subjects were premature, with a mean (±SD) gestational age of 28 ± 1 and 27 ± 1 weeks (P = .3) for LOW and CON, respectively. Thirty subjects completed follow-up (LOW = 15, CON = 15). There were no differences for ND and growth outcomes when LOW was compared with CON, with the exception of a higher 12-month follow-up cognitive scaled score in the LOW group (P = .02). CONCLUSION: A reduced SO dose did not adversely affect ND or growth in this cohort of preterm neonates. However, larger studies are needed to determine the long-term safety of SO dose reduction before this strategy can be adopted.

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.

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.

Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double-Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates.

BACKGROUND: This study's objective was to determine if parenteral cysteine when compared with isonitrogenous noncysteine supplementation increases erythrocyte reduced glutathione (GSH) in neonates at high risk for inflammatory injury. MATERIAL AND METHODS: Neonates with a score for neonatal acute physiology >10 requiring mechanical ventilation and parenteral nutrition (PN) were randomized in a double-blinded, placebo-controlled study to receive parenteral cysteine-HCl (CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/d for ≥7 days. A 6-hour [(13)C2] glycine IV infusion was administered at study week 1 to determine the fractional synthetic rate of GSH (FSR-GSH). RESULTS: Baseline characteristics were similar between the CYS (n = 17) and ISO groups (n = 21). Erythrocyte GSH and total glutathione concentrations, GSH:oxidized GSH (GSSG), and FSR-GSH after treatment were not different between groups. However, the CYS group had a larger individual positive change in GSH and total glutathione (infusion day - baseline) compared with the ISO group (P = .02 for each). After adjusting for treatment, a lower enrollment weight and rate of red blood cell transfusion were associated with a decreased change in total glutathione and GSH (P < .05 for each). CONCLUSION: When compared with isonitrogenous noncysteine supplementation, high-dose cysteine supplementation for at least 1 week in critically ill neonates resulted in a larger and more positive individual change in GSH. Smaller infants and those who received transfused blood demonstrated less effective change in GSH with cysteine supplementation. The benefit of cysteine remains promising and deserves further investigation.

Low-Dose Intravenous Soybean Oil Emulsion for Prevention of Cholestasis in Preterm Neonates.

BACKGROUND: Premature infants depend on intravenous fat emulsions to supply essential fatty acids and calories. The dose of soybean-based intravenous fat emulsions (S-IFE) has been associated with parenteral nutrition (PN)-associated liver disease. This study's purpose was to determine if low-dose S-IFE is a safe and effective preventive strategy for cholestasis in preterm neonates. MATERIALS AND METHODS: This is a multicenter randomized controlled trial in infants with a gestational age (GA) ≤29 weeks. Patients <48 hours of life were randomized to receive a low (1 g/kg/d) or control dose (approximately 3 g/kg/d) of S-IFE. The primary outcome was cholestasis, defined as a direct bilirubin ≥15% of the total bilirubin at 28 days of life (DOL) or full enteral feeds, whichever was later, after 14 days of PN. Secondary outcomes included growth, length of hospital stay, death, and major neonatal morbidities. RESULTS: In total, 136 neonates (67 and 69 in the low and control groups, respectively) were enrolled. Baseline characteristics were similar for the 2 groups. When the low group was compared with the control group, there was no difference in the primary outcome (69% vs 63%; 95% confidence interval, -0.1 to 0.22; P = .45). While the low group received less S-IFE and total calories over time compared with the control group (P < .001 and P = .03, respectively), weight, length, and head circumference at 28 DOL, discharge, and over time were not different (P > .2 for all). CONCLUSION: Compared with the control dose, low-dose S-IFE was not associated with a reduction in cholestasis or growth.

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.

Does hospital transfer predict mortality in very low birth weight infants requiring surgery for necrotizing enterocolitis?

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of infant mortality, and the most common reason for emergent surgery in very low birth weight (VLBW, < 1,500 g) infants. We investigated whether transfer for higher level of surgical care affects mortality in this population. METHODS: VLBW infants who underwent NEC surgery were reviewed retrospectively from the California Patient Discharge Linked Birth Cohort Database (1999-2007). Transfer for emergent operation was defined as surgery ≤2 days after transfer. Mortality was analyzed with multivariate logistic regression. RESULTS: Overall, 1,272 VLBW infants with surgical NEC were identified, with a 39% mortality. Transfer for operative care occurred in 406 (32%) infants. Unadjusted mortality was not increased for infants who were transferred compared with not transferred (37% vs. 40%; P = .25). Adjusted mortality for infants transferred for operative care did not differ from those who received operative care at their primary neonatal intensive care unit (odds ratio 0.75, 95% confidence interval 0.42-1.32). Lower birth weight, lack of prenatal care, peritoneal drainage as sole surgical intervention, and pulmonary interstitial emphysema/pulmonary hemorrhage were associated with increased odds of mortality (P < .05). CONCLUSION: VLBW infants with surgical NEC do not demonstrate increased risk of mortality when transferred emergently for operative care. Future efforts must engage health professionals caring for this vulnerable population to maximize resource allocation and safety.