Factors associated with enteral autonomy after reanastomosis in infants with intestinal failure and ostomy: A descriptive cohort study.

BACKGROUND: To determine variables associated with outcomes in infants with intestinal failure (IF) and ostomy following reanastomosis (RA). METHODS: A single-center, descriptive cohort study of 120 infants with IF and a stoma from January 2011 to December 2020 with subsequent RA during initial hospitalization. The primary outcome was achievement of enteral autonomy (EA) following RA. Other outcomes were duration of hospital stay, and mortality. Penalized logistic regression and linear regression were used for data analysis. RESULTS: The median gestational age was 26 weeks, and the median birth weight was 890 g. Three infants died. The median duration between ostomy creation and RA was 80 days (interquartile range; 62.5, 100.5). For each additional day of discontinuity, the odds of EA decreased by 2% (odds ratio [OR] = 0.980; 95% confidence interval [CI]: 0.962, 0.999; P = 0.038), and death increased by 4.2% (OR = 1.042; 95% CI: 1.010, 1.075; P = 0.009). For each additional mL/kg/day of enteral feeds at RA, the odds of EA increased by 7.5% (OR = 1.075; 95% CI: 1.027, 1.126, P = 0.002) and duration of hospital stay decreased by 0.35 days (slope coefficient = -0.351; 95% CI: -0.540, -0.163; P < 0.001). CONCLUSION: Shorter duration of intestinal discontinuity and enteral nutrition before RA could positively influence EA and duration of stay in infants with IF and ostomy following RA.

Cholestasis is associated with a higher rate of complications in both medical and surgical necrotizing enterocolitis.

OBJECTIVE: To evaluate the relationship between cholestasis and outcomes in medical and surgical necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective analysis of prospectively collected data from 1472 infants with NEC [455 medical (mNEC) and 1017 surgical (sNEC)] from the Children's Hospital Neonatal Database. RESULTS: The prevalence of cholestasis was lower in mNEC versus sNEC (38.2% vs 70.1%, p < 0.001). In both groups, cholestasis was associated with lower birth gestational age [mNEC: OR 0.79 (95% CI 0.68-0.92); sNEC: OR 0.86 (95% CI 0.79-0.95)] and increased days of parenteral nutrition [mNEC: OR 1.08 (95% CI 1.04-1.13); sNEC: OR 1.01 (95% CI 1.01-1.02)]. For both groups, the highest direct bilirubin was associated with the composite outcome mortality or length of stay >75th percentile [mNEC: OR 1.21 (95% CI 1.06-1.38); sNEC: OR 1.06 (95% CI 1.03-1.09)]. CONCLUSION: Cholestasis with both medical NEC and surgical NEC is associated with adverse patient outcomes including increased mortality or extreme length of stay.

Clinical Correlates of Cholestasis in Preterm Infants with Surgical Necrotizing Enterocolitis.

Background: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC). Methods: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not. Results: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%; p = 0.002), had higher mean C-reactive protein levels 2 weeks after NEC diagnosis (p = 0.009), had blood culture-positive sepsis [25 (40.3%) vs 4 (13.8%); p = 0.011], received parenteral nutrition (PN) for longer durations (108.4 ± 56.63 days vs 97.56 ± 56.05 days; p = 0.007), had higher weight-for-length z scores at 36 weeks' postmenstrual age [-1.0 (-1.73, -0.12) vs -1.32 (-1.76, -0.76); p = 0.025], had a longer length of hospital stay (153.7 ± 77.57 days vs 112.51 ± 85.22 days; p = 0.024), had intestinal failure more often (61% vs 25.0%, p = 0.003), had more surgical complications (50% vs 27.6%; p = 0.044), and had >1 complication (21% vs 3.4%; p = 0.031). Using linear regression, the number of days after surgery when feeds could be started [OR 15.4; confidence interval (CI) 3.71, 27.13; p = 0.009] and the postoperative ileus duration (OR 11.9, CI 1.1, 22.8; p = 0.03) were independently associated with direct bilirubin between 2 and 5 mg/dL (mild-moderate cholestasis) at 2 months of age. The duration of PN was independently associated with direct bilirubin >5 mg/dL (severe cholestasis) at 2 months of age in these patients. Conclusion: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer periods. Our data suggest that identification and prevention of risk factors such as sepsis and surgical complications and early feeds following NEC surgery may improve outcomes.

Current Practices, Challenges, and Recommendations in Enteral Nutrition After Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a neonatal disease with high mortality and morbidity. There is a lack of evidence-based recommendations on nutritional rehabilitation following NEC, and much of the current practice is guided by institutional policies and expert opinions. After a diagnosis of NEC, infants are exposed to an extended period of bowel rest and a prolonged course of antibiotics. Recognizing the patient characteristics that predict nutritional tolerance, early initiation of enteral nutrition, minimizing periods of bowel rest and antibiotic exposure, and standardization of dietary practices are the mainstay of post-NEC nutrition.

Current Patterns of Probiotic Use in U.S. Neonatal Intensive Care Units: A Multi-Institution Survey.

OBJECTIVE: Probiotic supplementation is associated with health benefits in preterm infants. The 2021 American Academy of Pediatrics (AAP) statement on probiotic use advised caution, citing heterogeneity and absence of federal regulation. We assessed the impact of the AAP statement and current institution-wide patterns of probiotic use across neonatal intensive care units (NICU) across the United States. STUDY DESIGN: A cross-sectional web-based institutional survey using REDCap was emailed to 430 Children's Hospital Neonatal Consortium (CHNC) and Pediatrix Medical Group institutions. The survey captured data on probiotic formulations, supplementation, initiation and cessation criteria, reasons for discontinuation, interest in initiating, and AAP statement's impact. RESULTS: Ninety-five (22.1%) hospitals, including 42/46 (91%) CHNC and 53/384 (14%) Pediatrix institutions, completed the survey. Thirty-seven (39%) currently use probiotics. Fourteen different probiotic formulations were reported. The common criteria for initiation were birth weight <1,500 g and gestational age <32 weeks. Parental consent or assent was obtained at only 30% of institutions. Five hospitals (11%) with prior probiotic use discontinued solely due to the AAP statement. Overall, 23 (24%) of hospitals indicated that the AAP statement significantly influenced their decision regarding probiotic use. Nineteen of 51 nonusers (37%) are considering initiation. CONCLUSION: Probiotic use in preterm infants is likely increasing in NICUs across the United States, but significant variability exists. The 2021 AAP statement had variable impact on NICUs' decision regarding probiotic use. The growing interest in adopting probiotics and the significant interhospital variability highlight the need for better regulation and consensus guidelines to ensure standardized use. KEY POINTS: · Probiotic use in preterm infants is likely increasing in U.S. NICUs, but clinical variability exists.. · The AAP statement on probiotic use in preterm infants had a modest impact on current practices.. · There's a need for better product regulation and consensus guidelines to ensure standardized use..

Patterns of lipid-injectable emulsion use in neonatal intensive care units across the United States: A multi-institution survey.

BACKGROUND: Lipid-injectable emulsions (ILEs) are a necessity for neonates dependent on parenteral nutrition (PN). In this manuscript, we describe the patterns of ILE use in neonatal intensive care units (NICUs) in the United States (US). METHODS: An electronic survey was sent to 488 NICUs across the US between December 2020 and March 2021. Survey fields included availability and utilization of various ILE in neonates. RESULTS: The response rate was 22% (107 out of 488). Soybean oil ILE (SO-ILE) and soybean oil, medium-chain triglycerides, olive oil, fish oil ILE (SO, MCT, OO, FO-ILE) had similar availability (87% vs 86%, respectively), and SO, MCT, OO, FO-ILE was more commonly used (SO-ILE, 71% vs SO, MCT, OO, FO-ILE, 86%). Fish oil-ILE (FO-ILE) was used by 55% of centers. SO-ILE was most frequently used with PN and needs <4 weeks without cholestasis (79%). The most common reason for SO, MCT, OO, FO-ILE use was cholestasis (71%). ILE minimization was used by 28% of SO-ILE and 22% of SO, MCT, OO, FO-ILE users; 95% of these centers restrict SO, MCT, OO, FO-ILE to doses ≤2 g/kg/day. Twenty-two percent of centers started FO-ILE at direct bilirubin of >5 mg/dl. CONCLUSION: The results of this survey reveal significant variability in ILE usage across the US. Lipid minimization with SO, MCT, OO, FO-ILE and initiation of FO-ILE for cholestasis at higher bilirubin thresholds are prevalent. Such reports are crucial for a better understanding of ILE use in the NICU and in future ILE development.

Short Bowel Syndrome and Dysmotility.

Due to recent advances, the mortality due to short bowel syndrome (SBS) has significantly decreased, but the morbidities are still high. Morbidities arising specifically due to dysmotility in SBS include feeding intolerance, prolonged dependence on parenteral nutrition, and associated complications such as intestinal failure associated liver disease, and bloodstream infections. The understanding of the pathogenesis of dysmotility in SBS has improved vastly. However, the tools to diagnose dysmotility in SBS in infants are restrictive, and the medical therapies to treat dysmotility are limited. Surgical techniques available for the treatment after failure of conservative management of dysmotility offer hope but carry their associated risks. The evidence to support either the medical therapies or the surgical techniques to treat dysmotility in SBS in children is scarce and weak. Development of newer therapies and efforts to build evidence to support currently available treatments in treating dysmotility in SBS is needed.

Nutritional Management of Short Bowel Syndrome.

Short bowel syndrome (SBS) of infancy is a cause of prolonged morbidity with intolerance to enteral feeding, specialized nutritional needs, and partial/total dependence on parenteral nutrition. These infants can benefit from individualized nutritional strategies to support and enhance the process of intestinal adaptation. Early introduction of enteral feeds during the period of intestinal adaptation is crucial, even though the enteral feedings may need to be supplemented with an effective, safe, and nutritionally adequate parenteral nutritional regimen. Newer generation intravenous lipid emulsions can be effective in preventing and treating intestinal failure-associated liver disease. Prevention of infection(s), pharmaceutical interventions to enhance bowel motility and prevent/mitigate bacteria overgrowth, and specialized multidisciplinary care to minimize the injury to other organs such as the liver, kidneys, and the brain can assist in nutritional rehabilitation and lower the morbidity in SBS.

Variability in antibiotic duration for necrotizing enterocolitis and outcomes in a large multicenter cohort.

OBJECTIVES: To evaluate variability in antibiotic duration for necrotizing enterocolitis (NEC) and associated clinical outcomes. STUDY DESIGN: Five-hundred ninety-one infants with NEC (315 medical; 276 surgical) were included from 22 centers participating in Children's Hospitals Neonatal Consortium (CHNC). Multivariable analyses were used to determine predictors of variability in time to full feeds (TFF) and length of stay (LOS). RESULTS: Median (IQR) antibiotic duration was 12 (9, 17) days for medical and 17 (14, 21) days for surgical NEC. Wide variability in antibiotic use existed both within and among centers. Duration of antibiotic therapy was associated with longer TFF in both medical (OR 1.04, 95% CI [1.01, 1.05], p < 0.001) and surgical NEC (OR 1.02 [1, 1.03] p = 0.046); and with longer LOS in medical (OR 1.03 [1.02, 1.04], p < 0.001) and surgical NEC (OR 1.01 [1.01, 1.02], p = 0.002). CONCLUSION: Antibiotic duration for both medical and surgical NEC remains variable within and among high level NICUs.

When the course deviates from expected: Misplacement of an epicutaneo-caval catheter in a neonate.

Central venous access, a common and essential component of the care of the critically ill neonate, is associated with complications such as infection, thrombosis, and bleeding. Unintentional arterial cannulation of a venous catheter is a rare but potentially dangerous complication. In the report, we describe the accidental cannulation of an artery with an epicutaneo-caval catheter in an extremely low birth weight infant. We discuss the physical and radiological findings that raise the suspicion of an arterial placement of a catheter, the diagnostic tools to confirm the misplacement, the potential complications, and strategies to prevent it.

In neonatal-onset surgical short bowel syndrome survival is high, and enteral autonomy is related to residual bowel length.

BACKGROUND: In an era of improved management and treatment options, this study aims to describe the long-term outcomes and factors predictive of outcomes of neonatal-onset intestinal failure (IF) due to surgical short bowel syndrome (SBS). METHODS: Retrospective, single-center cohort study of infants born between January 2011 and December 2018 with inclusion criteria: <44 weeks postmenstrual age at SBS diagnosis, <28 days on admission, parenteral nutrition dependence >60 days, and documented intestinal resection. Primary outcomes included survival and achievement of enteral autonomy (EA). Data analysis utilized Fisher.s exact test, Kruskal-Wallis test, survival analysis methods, Cox proportional hazards regression, linear regression and logistic regression. RESULTS: Ninety-five patients (males 56%) were studied with median follow-up of 38 months (IQR 19, 59). Survival at last follow-up was 96%, and EA was achieved in 85%. Forty-eight patients had documented residual bowel length (RBL) with median length of 49 cm (IQR 36, 80). Survival in patients with RBL of <30cm (n = 8), 30-59cm (n = 19), and >60cm (n = 21) was 100%, 95%, and 95% respectively. Shorter RBL was associated with longer time to achieve EA (p = 0.007), but not with survival (p = 0.81). Delay in achieving EA was associated with absence of ileocecal valve (p = 0.002) and bloodstream infections (p < 0.001). Peak conjugated bilirubin correlated with increased mortality (p = 0.002). CONCLUSION: Overall high rate of survival and achievement of EA was found in neonatal onset IF due to SBS. EA but not survival was correlated with RBL. Ileocecal valve, bloodstream infections, and conjugated bilirubin levels were the other predictive factors of outcomes.

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.

Small Proportion of Low-Birth-Weight Infants With Ostomy and Intestinal Failure Due to Short-Bowel Syndrome Achieve Enteral Autonomy Prior to Reanastomosis.

BACKGROUND: It is challenging to provide optimum nutrition in low-birth-weight (LBW) infants with short-bowel syndrome (SBS) and ostomy. This study aims to evaluate the clinical course of LBW infants with SBS and ostomy in response to enteral feeds, recognize characteristics associated with achievement of enteral autonomy prior to reanastomosis, and evaluate associated short-term outcomes. METHODS: A retrospective analysis of 52 LBW neonates with intestinal failure (IF) caused by SBS and ostomy treated in a neonatal intensive care unit from 2012 to 2018 was performed. Clinical characteristics and short-term outcomes were studied in relation to the location of the ostomy and the success with enteral feeding achieved prior to reanastomosis. RESULTS: Of the 52 infants with SBS, jejunostomy, ileostomy, and colostomy were present in 9, 40, and 3 infants, respectively. Fourteen (26.92%) infants achieved enteral autonomy transiently, and 7 (13.46%) sustained until reanastomosis. All 9 infants with jejunostomy were parenteral nutrition dependent, compared with 22 with ileostomy and none with colostomy (P = 0.002). Infants who achieved enteral autonomy showed lower incidence of cholestasis (P = 0.038) and better growth velocity (P = 0.02) prior to reanastomosis. CONCLUSIONS: A minority of LBW infants with SBS and ostomy achieved enteral autonomy prior to reanastomosis. Distal ostomy (ileostomy and colostomy), reduced cholestasis, and better growth were associated with achievement of enteral autonomy. Our report highlights the challenges in establishing enteral autonomy in LBW infants with IF and ostomy, and the feasibility of that approach in a minority of patients, with tangible benefits.

Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs.

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs [3/14 SO (21%), 3/14 MO15 (21%), and 2/14 FO100 (14%)] developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC versus no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC versus no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.NEW & NOTEWORTHY Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.

Incidence of spontaneous intestinal perforations exceeds necrotizing enterocolitis in extremely low birth weight infants fed an exclusive human milk-based diet: A single center experience.

BACKGROUND: Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are complications of extremely low birth weight (ELBW, ≤1000 g) infants. ELBW infants at Texas Children's Hospital receive an exclusive human milk-based diet, which has been associated with a reduction of NEC. OBJECTIVES: 1) Assess incidence of SIP and NEC (Stage II or greater) in ELBW infants receiving 100% human milk-based diet, 2) Describe mortality rates of ELBW infants with SIP and NEC. METHODS: Prospective single-center observational cohort study of ELBW infants born between 2010 and 2014 with SIP or NEC (exclusion: congenital anomalies and death within 48 h). RESULTS: Of 379 ELBW infants, 345 were eligible. Of these, 28 (8.1%) had SIP and 8 (2.3%) had NEC (medical n = 1, surgical n = 7). SIP infant mortality was 32% (n = 9) compared to 63% (n = 5) for NEC patients. Of SIP infants with PD (n = 25), 52% required subsequent exploratory laparotomy (LAP). Of NEC infants with peritoneal drainage (PD) (n = 2), both required subsequent LAP. CONCLUSION: Using an exclusive human milk-based diet, the incidence of SIP exceeds NEC in ELBW infants at our institution. This shows a changing trend in the incidence of these two diagnoses in the era of human milk, as NEC had previously been more prevalent in ELBW infants. More than half of infants who initially received PD later required LAP. There were no differences in survival outcomes in both SIP and NEC groups based on surgical management.

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.

Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs.

Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, and γ-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. The colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid-sensitive gram-positive bacteria.

Human Milk Supplements: Principles, Practices, and Current Controversies.

Human milk is the most optimal source of nutrition for preterm and term infants. However, in most preterm infants, breast milk fails to meet the energy needs of the newborn infant. Overwhelming evidence supports the fortification of breast milk in preterm infants to facilitate better short-term outcomes. Several single-nutrient and multinutrient breast milk supplements and fortifiers are used to improve the macronutrient and micronutrient content of breast milk. An individualized fortification strategy has the potential to offer better results compared with standard fortification strategies. Human milk-derived fortification is promising, but the benefits in exclusively human milk-fed preterm infants are unclear.

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.