Parenteral Nutrition-associated Liver Disease Research Articles

Exogenous Secretin Improves Parenteral Nutrition-associated Liver Disease in Rats.

Intestinal failure-associated liver disease (IFALD) is a feared and life-threatening complication in neonates with intestinal failure (IF) receiving long-term total parenteral nutrition (TPN). This study aims to investigate the effect of exogenous secretin on liver pathology and hepatic function in a rat model of PN-associated liver disease (PNALD). Male Sprague-Dawley rats underwent right jugular venous catheterization to receive 14-day continuous TPN therapy. All rats were allocated into 3 groups: the Control group (n = 8) did not have surgery or TPN and was fed standard rat chow ad libitum; the TPN group (n = 8) underwent catheter insertion and TPN treatment; and the TPN/S group (n = 8) also underwent catheter insertion, TPN treatment, and exogenous secretin treatment (2.5 nmol · kg · day) daily. Fourteen days after initial surgery, we collected the animals' liver and blood samples for further test. The TPN/S group had diminished direct bilirubin (TPN, 2.1 ± 0.7 μmol/L; TPN/S, 1.5 ± 0.2 μmol/L) and liver total bile acid levels (TPN, 144.5 ± 21.2 μmol/L; TPN/S, 123.4 ± 10.4 μmol/L) and improved histological outcomes compared with those in the TPN group. Exogenous secretin also enhanced the canalicular transporter (BSEP, 0.5-fold, P = 0.011) and inhibited the basolateral transporter (OSTA, -0.48-fold, P = 0.002; OSTB, -0.6-fold, P = 0.013) of liver bile acid. In this animal model of PNALD, secretin may improve cholestasis by enhancing canalicular transport, inhibiting the basolateral export of liver bile acid, and eventually decreasing the total bile acid level in the liver. Exogenous secretin treatment may potentially prevent and treat IFALD in IF patients relying on long-term TPN therapy.

Differential Metabolomic Analysis of Liver Tissues from Rat Models of Parenteral Nutrition-Associated Liver Disease.

Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure, but parenteral nutrition-associated liver disease (PNALD) limits its long-term use. The present study is aimed at determining which pathways are altered most notably in a rat model of PNALD. We randomly assigned male Sprague-Dawley (SD) rats into two different groups, whereby they received either enteral nutrition (EN) or PN. Liver tissues were harvested from all rats 7 days later for metabolomic profiling. The composition of primary conjugated bile acids was altered, the synthesis of polyunsaturated fatty acids was reduced, the conversion of pyruvate to acetyl-CoA was blocked, and the synthesis of phosphatidylcholine was inhibited in rats with PNALD. Riboflavin, which is involved in the electron transfer process in the mitochondrial electron transport chain, was remarkably decreased in PNALD rats. A deficiency of polyunsaturated fatty acids, riboflavin, choline, and taurine might be involved in the progression of PNALD. The implications of these findings for the field of medicine are that supplementation with polyunsaturated fatty acids, riboflavin, choline, and taurine might have potential as therapeutic strategies for PNALD and also shed light on the mechanisms of PNALD.

Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp.

Parenteral Nutrition (PN) Associated Liver Disease (PNALD) affects up to 60% of neonates; however, techniques for diagnosing and monitoring disease progression remain limited. The neonatal baboon model may provide a unique opportunity to identify serologic markers associated with this disease. The purpose of this study was to investigate if Hyaluronic Acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP1), Amino-terminal Propeptide of Type-III Collagen (PIIINP) and Enhanced Liver Fibrosis (ELF) score associate with histological liver disease in neonatal baboons exposed to PN. Preterm baboons delivered via c-section at 67% gestation received PN for 14 days with or without Intralipid (PRT+IL, PRT-IL, respectively) or were sacrificed after birth (PRTCTR). Term baboons were sacrificed after birth (TERMCTR) or survived 14 days (TERM+14d). Serum HA, TIMP1, and PIIINP concentrations were measured by ELISA. A blinded pathologist assigned liver histological scores following necropsy. HA increased 9.1-fold, TIMP1 increased 2.2-fold, and ELF score increased 1.4-fold in PRT-IL compared to PRTCTR. ALT, AST, and GGT were within normal limits and did not vary between groups. A trend towards increased fibrosis was found in PRT-IL baboons. Microvesicular hepatocyte steatosis and Kupffer cell hypertrophy were elevated in PRT-IL vs PRTCTR. HA and TIMP1 were significantly elevated in preterm baboons with early histological findings of liver disease evidenced by hepatic steatosis, Kupffer cell hypertrophy and a trend towards fibrosis whereas traditional markers of liver disease remained normal. These novel markers could potentially be utilized for monitoring early hepatic injury in neonates.

Translational Advances in Pediatric Nutrition and Gastroenterology: New Insights from Pig Models.

Pigs are increasingly important animals for modeling human pediatric nutrition and gastroenterology and complementing mechanistic studies in rodents. The comparative advantages in size and physiology of the neonatal pig have led to new translational and clinically relevant models of important diseases of the gastrointestinal tract and liver in premature infants. Studies in pigs have established the essential roles of prematurity, microbial colonization, and enteral nutrition in the pathogenesis of necrotizing enterocolitis. Studies in neonatal pigs have demonstrated the intestinal trophic effects of akey gut hormone, glucagon-like peptide 2 (GLP-2), and its role in the intestinal adaptation process and efficacy in the treatment of short bowel syndrome. Further, pigs have been instrumental in elucidating the physiology of parenteral nutrition-associated liver disease and the means by which phytosterols, fibroblast growth factor 19, and a new generation of lipid emulsions may modify disease. The premature pig will continue to be a valuable model in the development of optimal infant diets (donor human milk, colostrum), specific milk bioactives (arginine, growth factors), gut microbiota modifiers (pre-, pro-, and antibiotics), pharmaceutical drugs (GLP-2 analogs, FXR agonists), and novel diagnostic tools (near-infrared spectroscopy) to prevent and treat these pediatric diseases.

Development of Parenteral Nutrition-Associated Liver Disease and Other Adverse Effects in Neonates Receiving SMOFlipid or Intralipid.

Intravenous lipid emulsions (ILEs) are a risk factor for parenteral nutrition-associated liver disease (PNALD) in the neonatal population. Current literature supports the use of SMOFlipid (4-oil ILE), a fish oil-containing lipid emulsion, for the reversal of PNALD. However, there is little information about the use of 4-oil ILEs for preventing PNALD. The purpose of this study is to examine the safety of a 4-oil ILE in neonates and its effectiveness in preventing PNALD among neonates compared with Intralipid (a soybean-oil, SO-ILE). This is an observational, cohort, comparative safety study, conducted in a level III neonatal intensive care unit. Participants include neonates who received a 4-oil ILE in their parenteral nutrition (PN) formula, who were matched with historical data of patients who received an SO-ILE, in a 1:3 fashion (4-oil ILE:SO-ILE). The primary outcome of this study is the presence of PNALD (defined as direct bilirubin > 2 mg/dL) after initiation of PN. A total of 1332 participants (333 4-oil ILE vs 999 SO-ILE) were included in the data analysis, and PNALD was found to occur in 1.8% of patients in the 4-oil ILE group and 3.6% of patients in the SO-ILE group (Relative risk (RR) 0.5; 95% CI, 0.21-1.18). The decrease in the incidence of PNALD among the 4-oil ILE group compared with the SO-ILE group indicates a 4-oil ILE may have a hepatoprotective effect.

Suppression of IRE1α Attenuated the Fatty Degeneration in Parenteral Nutrition-Related Liver Disease (PNALD) Cell Model.

Aims To model the parenteral nutrition-associated liver disease (PNALD) in rat normal hepatocytes BRL and investigate the role of endoplasmic reticulum stress- (ERS-) related IRE1α signal in the process of PNALD. Methods The BRL cells were treated with different concentrations of soybean oil emulsion (SO) to induce hepatocyte fatty degeneration. The PNALD cell disease model was further confirmed by analysis of Oil Red O staining and biochemical parameters. Next, the IRE1α signal in the process of PNALD. α signal in the process of PNALD. α signal in the process of PNALD. α signal in the process of PNALD. Results The results of Oil Red O staining indicated that the PNALD was successfully established in BRL cells and the CCK-8 data indicated which 0.6% that SO was further applied to the experiment owing to its better induction of PNALD and less toxicity to the cells. Besides, the value of biochemical parameters (TBIL, DBIL, ALT, and AST) was also elevated in the SO group compared with the NG group. After knockdown of IRE1α signal in the process of PNALD. α signal in the process of PNALD. Conclusion IRE1α was induced in PNALD cell model and suppression of IRE1α resulted in reduced steatosis in this cell disease model. Taken together, our data suggested that the IRE1α pathway may be involved in the development of PNALD.α signal in the process of PNALD. α signal in the process of PNALD. α signal in the process of PNALD.

Parenteral Nutrition-Associated Liver Disease.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-nowak a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-nowak an interview with the author.

Early parenteral nutrition in neonates with congenital diaphragmatic hernia.

The ideal nutritive strategy for a neonate with congenital diaphragmatic hernia (CDH) has not been elucidated. The purpose of this study was to investigate the efficacy of early parenteral nutrition (PN) in CDH neonates. Thirty-five CDH neonates admitted to a single hospital from January 2005 to December 2014 were retrospectively reviewed. For the first 4 years of the study period, neonates received non-early PN (n-EPN) (2005-2008, amino acids [AA] <1.0g/kg/day, no lipids administered). After the transitional period (TP) (2009-2011, AA 1.0-2.5g/kg/day, lipid 1.0g/kg/day), early PN (EPN) (2011-2014, AA ≥3.0g/kg/day, lipid 1.0g/kg/day) was performed. We investigated the clinical effect of PN for growth-associated clinical variables and the outcomes. The first day of AA administration was late in the n-EPN period (6.0 ± 4.6, 0.0 ± 0.8, 0.1 ± 0.3 ; n-EPN, TP, EPN: in order). The final day of PN (11.0 ± 3.7, 9.2 ± 4.0, 12.4 ± 3.9) and the first day of enteral feeding (4.5 ± 1.9, 4.3 ± 1.4, 4.5 ± 3.2), the first day of full milk feeding (100 mL/kg/day) (10.8 ± 5.4, 9.2 ± 2.3, 11.5 ± 3.5) were statistically equal in every period. The date and body weight at discharge showed no significant differences among the three groups, but the weight-gain rate from birth to discharge was higher in the EPN group than in the n-EPN group (P = 0.023). The rate of inhaled nitric oxide (NO) gas administration and the duration of ventilation showed no significant differences among the three groups. Severe PN-associated liver disease was not noted during the observation period. Early PN for CDH neonates promotes weight gain in the neonatal intensive-care unit. The long-term efficacy and safety of EPN for CDH neonates should be elucidated by additional studies.

P128 INCIDENCE AND OUTCOMES OF HOME PARENTERAL NUTRITION IN PATIENTS WITH CROHN’S DISEASE IN OMLSTED COUNTY, MINNESOTA, USA

Abstract Introduction Patients (pts) with Crohn’s disease (CD) undergoing multiple surgeries are at risk of extensive bowel resections, short bowel syndrome (SBS) and malnutrition and may need home parenteral nutrition (HPN). The aim of our study was to estimate the incidence of HPN use in pts with CD in a population-based cohort, and to assess clinical outcomes and complications associated with nutritional intervention. Methods This study was a retrospective population-based cohort using Rochester Epidemiology Project to identify pts who were diagnosed with CD between 1970 and 2011 in Olmsted County, MN. To identify the individuals who required HPN, these Pts were crossed against the list of those who enrolled in the local HPN program. Descriptive statistics were used to evaluate incidence and clinical outcomes. Results Four hundred twenty nine pts with CD were diagnosed in Olmsted County between 1970 and 2011. Of these, 14 received HPN between 1992 and 2018. The pts were followed for a median of 16.85 years after diagnosis of CD (interquartile (IQR), 12.25–24.70) and required HPN a median of 7.67 years after diagnosis (IQR,1.6–15.89). Among the 14 receiving HPN, 85.71% were females. Eleven (78.57%) had moderate to severe CD and 12 (85.71%) pts involved with fistulizing disease. Crohn’s disease involved the ileum in 92.86%, colon in 71.43%, and proximal GI in 14.29% of the pts. Thirteen (92.86%) pts underwent surgery primarily due to obstruction (84.62%). Other indication included: failure of medical therapy (46.15%), fistulizing disease (46.15%), severe pain (30.77%), abdominal abscess (23.08%), bleeding (15.38%), and necrosis (15.38%). Median number of bowel resections was 4 (range, 0–7). Twelve pts (85.71%) had a stoma placed. The median duration of HPN was 2.48 years (range, 0.11–16.36). Indications for HPN included SBS in 64.28%, malnutrition in 28.57% and bowel rest in 21.43%. The mean number of hospitalizations after the start of HPN was 5 (range, 0–20). Catheter-related bloodstream infections occurred in 10 (71.43%) pts, and 3 (21.43%) had a thrombosis. Four pts had osteoporosis and 2 had osteopenia. Parenteral nutrition-associated liver disease occurred in 2 (14.29%) of pts. The pts’ body weight increased a median of 2.5 kilograms (kg) 6 months after the start of HPN but decreased a median of 1 kg at 12 months. Four (30.77%) pts were on HPN at time of last follow-up. Five (35.71%) pts deceased mainly due to CD. Conclusion Less than 4% of pts with CD need HPN. Most pts on HPN have moderate to severe disease who have undergone extensive bowel resection with resultant SBS and malnutrition. Approximately 70% were able to discontinue HPN. Interestingly, after 6 months, pts lost most of the weight they gained during the first 6 months of HPN. It was possible that this was due to noncompliance, or increased metabolic needs because of active disease.

TGR5 signaling mitigates parenteral nutrition-associated liver disease.

Bile acid receptors regulate the metabolic and immune functions of circulating enterohepatic bile acids. This process is disrupted by administration of parenteral nutrition (PN), which may induce progressive hepatic injury for unclear reasons, especially in the newborn, leading to PN-associated liver disease. To explore the role of bile acid signaling on neonatal hepatic function, we initially observed that Takeda G protein receptor 5 (TGR5)-specific bile acids were negatively correlated with worsening clinical disease markers in the plasma of human newborns with prolonged PN exposure. To test our resulting hypothesis that TGR5 regulates critical liver functions to PN exposure, we used TGR5 receptor deficient mice (TGR5-/-). We observed PN significantly increased liver weight, cholestasis, and serum hepatic stress enzymes in TGR5-/- mice compared with controls. Mechanistically, PN reduced bile acid synthesis genes in TGR5-/-. Serum bile acid composition revealed that PN increased unconjugated primary bile acids and secondary bile acids in TGR5-/- mice, while increasing conjugated primary bile acid levels in TGR5-competent mice. Simultaneously, PN elevated hepatic IL-6 expression and infiltrating macrophages in TGR5-/- mice. However, the gut microbiota of TGR5-/- mice compared with WT mice following PN administration displayed highly elevated levels of Bacteroides and Parabacteroides, and possibly responsible for the elevated levels of secondary bile acids in TGR5-/- animals. Intestinal bile acid transporters expression was unchanged. Collectively, this suggests TGR5 signaling specifically regulates fundamental aspects of liver bile acid homeostasis during exposure to PN. Loss of TGR5 is associated with biochemical evidence of cholestasis in both humans and mice on PN.NEW & NOTEWORTHY Parenteral nutrition is associated with deleterious metabolic outcomes in patients with prolonged exposure. Here, we demonstrate that accelerated cholestasis and parental nutrition-associated liver disease (PNALD) may be associated with deficiency of Takeda G protein receptor 5 (TGR5) signaling. The microbiome is responsible for production of secondary bile acids that signal through TGR5. Therefore, collectively, these data support the hypothesis that a lack of established microbiome in early life or under prolonged parenteral nutrition may underpin disease development and PNALD.

Incidence of Parenteral Nutrition-Associated Liver Disease in Infants on Prolonged Parenteral Nutrition with a Soybean-Based Lipid Emulsion: A 7-Year Experience

Parenteral nutrition associated liver disease (PNALD) is a significant complication in infants receiving long-term parenteral nutrition (PN). Chronic administration of PN has been associated with its development. Our purpose is to characterize our incidence of PNALD over an extended period and identify risk factors for its development, including administration of soybean-based injectable lipid emulsions (ILEs) as we transit to novel ILEs in our practice. Infants receiving 30 days or more of PN were included. PNALD was defined as a direct bilirubin ≥ 2 mg/dL. Data collected included: patient demographics, clinical and enteral feeding characteristics. Macronutrient intake was recorded using these cut-offs: glucose infusion rate (GIR) of ≤14 mg/kg/min or above, protein doses of ≤3 g/kg/day or above and lipid doses of ≤2 g/kg/day or above. A total of 349 infants were included, with an annual incidence of PNALD ranging between 34% - 54%. Infants with PNALD were younger by gestation (27 vs. 29.5 weeks) and smaller by birthweight (900 vs. 1248 grams). Sepsis, GI disease including necrotizing enterocolitis and bowel resection were significantly associated with an increased risk for development of PNALD. PNALD infants received lower protein doses (3.0 vs 3.3 g/kg/day, p = 0.014) while receiving higher GIR (11.4 vs 10.7 mg/kg/min, p = 0.012) compared to non-PNALD infants. Low birth weight, sepsis and bowel resection remain strong indicators of risk for PNALD. No single macronutrient increased our infants’ risk for PNALD. The use of newer ILEs when available should be evaluated for their impact on PNALD development.

Evaluation of parenteral nutrition-associated liver disease in surgical infants for necrotizing enterocolitis

The purpose of this study was to determine the factors associated with parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC) and followed up the postoperative outcomes for long term parenteral nutrition (PN).This study included a retrospective review of 87 infants with NEC and managed surgically from July 2007 to May 2017 at the Children's Hospital, Chongqing Medical University. Clinical data and procedure information were collected and analyzed.Among the infants included, 16.1% of patients developed PNALD. Multivariable logistic regression analysis revealed progressive clinical deterioration (OR, 5.47; 95% CI, 1.10–26.96; P = .037) was independent risk factor for PNALD whereas congenital heart disease (OR, 0.068; 95% CI, 0.008–0.55; P = .012) presentation served as a protective factor.The current data suggested the distinct disease process for cardiac patients with NEC, which might help in the prevention and treatment of PNALD for patients with NEC.

Review of parenteral nutrition-associated liver disease.

Parenteral nutrition has been widely used in patients whose gastrointestinal tract is anatomically or physiologically unavailable for sufficient food intake. It has been considered lifesaving but is not without adverse effects. It has been proven to cause liver injury through different mechanisms. We present a review of parenteral nutrition-associated liver disease.

Mechanisms of Parenteral Nutrition-Associated Liver and Gut Injury.

Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN-associated liver disease or intestinal failure-associated liver disease. Recent studies into gut-systemic cross talk via the bile acid-regulated farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5-glucagon-like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN-associated injury. It has also been shown that the composition of ω-6/ω-3 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies.

Effects of total parenteral nutrition on drug metabolism gene expression in mice

Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid® and omega-3 rich Omegaven® are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. In this study, either Intralipid®- or Omegaven®-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed, glutathione (GSH) levels were measured, and protein levels for two key drug metabolism genes were determined. Overall, the expression of most genes was downregulated by Intralipid®-based TPN (Gstp1, Gstm1, 3, 6, Nqo1, Ho-1, Mt-1, Gclc, Gclm, Cyp2d9, 2f2, 2b10, and 3a11). Omegaven® showed similar results as Intralipid® except for preserving the expression of Gstm1 and Cyp3a11, and increasing Ho-1. Total GSH levels were decreased by Intralipid®, but increased by Omegaven®. CYP3A11 protein levels were increased by Omegaven®. In conclusion, TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice. However, Omegaven® preserved expression of Cyp3a11, suggesting another beneficial effect of Omegaven® in protecting liver functions.

Incidence and risk factors of parenteral nutrition-associated liver disease in hospitalized adults: A prospective cohort study

Parenteral nutrition-associated liver disease (PNALD) is a common complication in patients receiving parenteral nutrition (PN). Few studies have investigated the incidence and risk factors of PNALD in adult patients receiving PN with newer generation intravenous lipid emulsions. The aim of this study was to investigate the incidence and risk factors of PNALD in hospitalized adult patients. Patients expected to receive PN for more than 14 days and have normal liver tests at baseline during September 2016 to February 2017 were enrolled. All patients were followed until there were liver test abnormalities. Incidence, onset and characteristics of PNALD, calories intake, amount of fat and carbohydrate, types of fat, nutrition status, and incidence of infection were evaluated. Forty-four adults were recruited. The incidence of PNALD was 59.1% (22.7% steatosis, 34.1% cholestasis, and 2.3% mixed type). Median onset of PNALD was 12.5 days (range: 4-42) and the onset was not significantly different between each subtype. In multiple regression analysis, severe malnutrition and amount of carbohydrate were independent risk factors for PNALD with an odds ratio of 13.25 (95% CI: 1.37-128.24; p=0.026) and 21.61 (95% CI: 1.81-258.56; p=0.015), respectively. PNALD was common in this group of patients. In contrast to previous studies, cholestasis was more common than steatosis, and the median onset was not different between each subtype. In severely malnourished patients, physicians need to exercise caution and monitor for PNALD intensively, and overfeeding of carbohydrate should be avoided to prevent PNALD from occurring.

Modified Rat-Tail-Fixed Model of Parenteral Nutrition to Study Liver Injury

For patients with intestinal failure, parenteral nutrition (PN) is a life-saving therapy. Unfortunately, PN does have serious adverse effects. The purpose of our study was to establish a tail-fixed and reproducible animal model of PNALD in which to explore the pathogenesis and evaluate various potential therapeutic manipulations as potential methods of treatment or prevention. Forty SD rats were randomly assigned to parenteral nutrition group or control group. A central venous catheter was inserted for intravenous infusion of a total parenteral nutrition solution (TPN group) or saline (control group) for 1 week or 2 weeks. Survival rate, hepatic biochemical tests, and liver pathology were analyzed. There was no significant difference in survival rate between the two groups at 1 and 2 weeks. The TPN group showed significant increases in direct bilirubin, total bilirubin, and serum aminotransferase than the control group (P < 0.05). Livers in the TPN group had severe, diffuse involvement of hepatocytes by macrovesicular and microvesicular steatosis. The pathological scores were significantly higher in the TPN group than the control group (P < 0.05). The model provides the opportunity to further investigate pathogenesis and treatment of parenteral nutrition–associated liver disease.

Safety and efficacy of mucous fistula refeeding in low-birth-weight infants with enterostomies.

To investigate the safety and efficacy of mucous fistula refeeding (MFR) in low-birth-weight infants. Between December 2006 and December 2018, medical records of low-birth-weight infants who underwent small bowel enterostomy formation in the neonatal period and subsequent stoma closure at our institution were retrospectively reviewed. Patients were assigned to "refeeding" (RF) and "non-refeeding" (NRF) groups, which were compared for patient characteristics and clinical outcomes. We also cultured the proximal stoma output over time in the RF group and reviewed changes in the flora to evaluate the safety of refeeding. In the RF group, compared with that before refeeding, there was significantly more rapid weight gain after refeeding (17.7 vs 10.6g/day; P = 0.002). Median total time of parenteral nutrition (PN) was 25 and 87days in the RF and NRF groups, respectively (P = 0.001). The number of patients who developed PN-associated liver disease (PNALD) was smaller in the RF group (P = 0.12). No complications of MFR were noted and no pathogenic bacteria were cultured. MFR was able to diminish the need for PN, which potentially decreased the incidence of PNALD, and was safe as there were no complications of the refeeding process.

Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants

Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants

Re-feeding versus discarding gastric residuals to improve growth in preterm infants.

Routine monitoring of gastric residuals in preterm infants on gavage feeds is a common practice in many neonatal intensive care units and is used to guide the initiation and advancement of feeds. No guidelines or consensus is available on whether to re-feed or discard the aspirated gastric residuals. Although re-feeding gastric residuals may replace partially digested milk, gastrointestinal enzymes, hormones, and trophic substances that aid in digestion and promote gastrointestinal motility and maturation, re-feeding abnormal residuals may result in emesis, necrotising enterocolitis, or sepsis. To assess the efficacy and safety of re-feeding compared to discarding gastric residuals in preterm infants. The allocation should have been started in the first week of life and should have been continued at least until the baby reached full enteral feeds. The investigator could have chosen to discard the gastric residual in the re-feeding group, if the gastric residual quality was not satisfactory. However, the criteria for discarding gastric residual should have been predefined.To conduct subgroup analysis based on gestational age (≤ 27 weeks, 28 weeks to 31 weeks, ≥ 32 weeks), birth weight (< 1000 g, 1000 g to 1499 g, ≥ 1500 g), type of milk (human milk or formula milk), quality of the gastric residual (fresh milk, curded milk, or bile-stained gastric residual), volume of gastric residual replaced (total volume, 50% of the volume, volume of the next feed, or prespecified volume, irrespective of the volume of the aspirate, e.g. 2 mL, 3 mL), and whether the volume of gastric residual that is re-fed is included in or excluded from the volume of the next feed (see "Subgroup analysis and investigation of heterogeneity"). We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE via PubMed (1966 to 19 February 2018), Embase (1980 to 19 February 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 19 February 2018). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised controlled trials that compared re-feeding versus discarding gastric residuals in preterm infants. Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported the risk ratio and risk difference for dichotomous data, and the mean difference for continuous data, with respective 95% confidence intervals. We used the GRADE approach to assess the quality of evidence. We found one eligible trial that included 72 preterm infants. This trial was not blinded.We are uncertain as to the effect of re-feeding gastric residual on efficacy outcomes such as time to regain birth weight (mean difference (MD) 0.40 days, 95% confidence interval (CI) -2.89 to 3.69 days; very low quality evidence), time to reach enteral feeds ≥ 120 mL/kg/d (MD -1.30 days, 95% CI -2.93 to 0.33 days; very low quality evidence), number of infants with extrauterine growth restriction at discharge (risk ratio (RR) 1.29, 95% CI 0.38 to 4.34; very low quality evidence), duration of total parenteral nutrition (MD -0.30 days, 95% CI -2.07 to 1.47 days; very low quality evidence), and length of hospital stay (MD -1.90 days, 95% CI -25.27 to 21.47 days; very low quality evidence).Similarly, we are uncertain as to the effect of re-feeding gastric residual on safety outcomes such as incidence of stage 2 or 3 necrotising enterocolitis and/or spontaneous intestinal perforation (RR 0.71, 95% CI 0.25 to 2.04; very low quality evidence), number of episodes of feed interruption lasting ≥ 12 hours (RR 0.80, 95% CI 0.42 to 1.52; very low quality evidence), or mortality before discharge (RR 0.50, 95% CI 0.14 to 1.85; low-quality evidence). We are uncertain as to the effect of re-feeding gastric residual in the subgroups of human milk-fed and formula-fed infants. We found no data on other outcomes such as linear and head growth during hospital stay, postdischarge growth, number of infants with parenteral nutrition-associated liver disease, and neurodevelopmental outcomes. We found only limited data from one small unblinded trial on the efficacy and safety of re-feeding gastric residuals in preterm infants. The quality of evidence was low to very low. Hence, available evidence is insufficient to support or refute re-feeding of gastric residuals in preterm infants. A large, randomised controlled trial is needed to provide data of sufficient quality and precision to inform policy and practice.