Impact of disease-specific volume and hospital transfer on outcomes in gastroschisis.

BACKGROUND: Gastroschisis, a surgical condition requiring complex interdisciplinary care, may benefit from treatment at higher volume centers. Recent studies on surgical volume and outcomes have conflicting findings. METHODS: Data were collected prospectively on newborns ≥1500 g with gastroschisis born 2009-2015, admitted to 159 US centers, and separated into terciles based on number of annual gastroschisis repairs. Infants transferred after gastroschisis repair were excluded. RESULTS: There were 4663 infants included: 307 from 53 low, 1201 from 55 medium, and 3155 from 51 high volume centers. Infants at high volume centers had higher rates of intestinal atresia (P = 0.04) and outborn status (P < 0.0001). Outborn infants (N = 1134) had higher rates of gastrostomy/jejunostomy placement (P < 0.001). Mortality was universally low (2.0% low, 2.4% medium, and 1.7% high; 2.0% outborn and 1.9% inborn). On multivariate analysis, mortality, sepsis rates, and length of stay did not differ by center volume. Outborn status was associated with longer length of stay (P = 0.001), not mortality or sepsis. CONCLUSION: Infant characteristics and management vary based on gastroschisis surgical volume and transfer status. Center volume and early transfers were not associated with mortality. Further investigation to identify subsets of gastroschisis infants who would benefit from care at higher volume centers is warranted. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level II.

Growth morbidity in extremely low birth weight survivors of necrotizing enterocolitis at discharge and two-year follow-up.

PURPOSE: The purpose of this study was to examine postnatal growth outcomes and predictors of growth failure at 18-24months corrected age among extremely low birth weight (ELBW) survivors of necrotizing enterocolitis (NEC) compared to survivors without NEC. METHODS: Data were collected prospectively on ELBW (22-27weeks gestation or 401-1000g birth weight) infants born 2000-2013 at 46 centers participating in the Vermont Oxford Network follow-up project. Severe growth failure was defined as <3rd percentile weight-for-age. RESULTS: There were 9171 evaluated infants without NEC, 416 with medical NEC, and 462 with surgical NEC. Rates of severe growth failure at discharge were higher among infants with medical NEC (56%) and surgical NEC (61%), compared to those without NEC (36%). At 18-24months follow-up, rates of severe growth failure decreased and were similar between without NEC (24%), medical NEC (24%), and surgical NEC (28%). On multivariable analysis, small for gestational age, chronic lung disease, severe intraventricular hemorrhage or cystic periventricular leukomalacia, severe growth failure at discharge, and postdischarge tube feeding predicted <3rd percentile weight-for-age at follow-up. CONCLUSIONS: ELBW survivors of NEC have higher rates of severe growth failure at discharge. While NEC is not associated with severe growth failure at follow-up, one quarter of ELBW infants have severe growth failure at 18-24months. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: II.

High Rates of Positive Severe Combined Immunodeficiency Screening Among Newborns with Severe Intestinal Failure.

PURPOSE: Severe combined immunodeficiency (SCID) screening by T-cell receptor excision circles (TREC) has been part of Massachusetts routine newborn screening since 2009. Tetratricopeptide repeat domain 7A gene (TTC7A) mutations responsible for hereditary multiple intestinal atresia with combined immunodeficiency (MIA-CID) were also recently identified. We reviewed newborn SCID screening among infants with intestinal failure and correlated results with patient characteristics and outcomes. METHODS: Records of infants with severe intestinal failure and available newborn screen results treated at a single center 2009-2016 were reviewed retrospectively. Patients with 1 or more positive SCID screens (<252 TREC copies/µL) were compared with those without positive screens. TREC copies/µL were compared with population norms. RESULTS: Of 70 included infants, 34% had newborn screens with TREC <252 copies/µL, compared with 0.3% of the general population; TREC levels for the cohort were lower than the general population (p<0.001). Of those with positive screens, 42% had prior or subsequent negative screening, 8% had no further workup, and 50% had flow cytometry showing: severe T-cell lymphopenia (absolute CD3+ <1500 cells/mcL) in 8, 3 of whom had TTC7A mutation-associated MIA-CID. Four had CD3+ >1500 cells/mcL. MIA-CID patients had the lowest serum citrulline in the cohort; 4 of the 8 patients with CD3+ <1500 cells/mcL on flow cytometry had newborn screening notable for severe hypocitrullinemia (<3 µM). CONCLUSION: Infants with intestinal failure have lower TREC copies/µL than the general population; one-third had levels concerning for SCID, and 11% were diagnosed with severe T-cell lymphopenia. The clinical implications and etiology of this phenomenon remain unknown, but may be related to hypocitrullinemia.

Whole Body Protein Turnover and Net Protein Balance After Pediatric Thoracic Surgery: A Noninvasive Single-Dose 15 N Glycine Stable Isotope Protocol With End-Product Enrichment.

BACKGROUND: We used the 15 N glycine urinary end-product enrichment technique to quantify whole body protein turnover following thoracic surgery. MATERIALS AND METHODS: A single dose of 15 N glycine (2 mg/kg) was administered orally on postoperative day 1 to children (1-18 years) following thoracic surgery. 15 N enrichment of ammonia and urea was measured in mixed urine after 12 and 24 hours, respectively, and protein synthesis, breakdown, and net balance determined. Nitrogen balance (dietary intake minus urinary excretion) was calculated. Urinary 3-methylhistidine:creatinine ratio was measured as a marker of skeletal muscle protein breakdown. RESULTS: We enrolled 19 subjects-median (interquartile range): age, 13.8 years (12.2-15.1); weight, 49.2 kg (38.4-60.8)-who underwent thoracotomy (n = 12) or thoracoscopic (n = 7) surgery. Protein synthesis and breakdown by 15 N enrichment were 7.1 (5.5-9) and 7.1 (5.6-9) g·kg-1 ·d-1 with ammonia (12 hours) as the end product, and 5.8 (3.8-6.7) and 6.7 (4.5-7.6) with urea (24 hours), respectively. Net protein balance by the 15 N glycine and urinary urea nitrogen methods were -0.34 (-0.47, -0.3) and -0.48 (-0.65, -0.28) g·kg-1 ·d-1 , respectively (rs = 0.828, P < .001). Postoperative change in 3-methylhistidine:creatinine ratio did not correlate significantly with protein breakdown or balance. CONCLUSION: The single-dose oral administration of 15 N glycine stable isotope with measurement of urinary end-product enrichment is a feasible and noninvasive method to investigate whole body protein turnover in children. After major surgery, children manifest increased protein turnover and net negative balance due to increased protein breakdown.

Nutrition Delivery and Growth Outcomes in Infants With Gastroschisis.

BACKGROUND: We aimed to describe nutrient intake and growth in infants with gastroschisis and identify factors associated with impaired growth. METHODS: Retrospective study of neonates who underwent gastroschisis repair from 2010 to 2015. Nutrient intake and weight-for-age z scores (WAZ) were recorded. RESULTS: Data from 60 eligible infants with median (Q1, Q3) gestational age of 36 weeks (35, 37) and birth weight 2418 g (2098, 2665) were analyzed. Median WAZ decreased from -0.71 (-1.08, -0.17) at birth to -1.08 (-1.58, -0.63) at discharge (P < .001); 30% experienced a >1.0 decline in WAZ. Parenteral nutrition (PN) was initiated soon after birth, and 14 (23%) patients had severe intestinal failure. Fourteen patients (23%) experienced central line-associated bloodstream infection (CLABSI) at a rate of 5.0 per 1000 catheter days. Factors independently associated with lower discharge WAZ and greater WAZ decline were CLABSI (P = .02) and prematurity (P = .02). By day 7, energy and protein intake were 90-100 kcal/kg/day and 3 g/kg/day, respectively. Median age to achieve enteral autonomy was 36 days (22, 82). Atresias, CLABSI, prematurity, and staged closure were associated with delayed enteral autonomy (P < .01). Among 34 patients with 1-year follow-up, WAZ improved from -1.16 (-1.74, -0.65) at discharge to 0.19 (-0.80, 0.61) at 12 months (P < .001). CONCLUSION: Infants with gastroschisis are dependent on PN and have a significant decline in WAZ during their hospital stay, predicted by prematurity and CLABSI. Efforts to prevent CLABSI and optimize enteral autonomy must be prioritized in this cohort.

Long-term outcomes of pediatric intestinal failure.

Management of pediatric intestinal failure has evolved in recent decades, with improved survival since the advent of specialized multidisciplinary intestinal failure centers. Though sepsis and intestinal failure associated liver disease still contribute to mortality, we now have growing data on the long-term outcomes for this population. While intestinal adaptation and parenteral nutrition weaning is most rapid during the first year on parenteral support, achievement of enteral autonomy is possible even after many years as energy and protein requirements decline dramatically with age. Intestinal transplant is an option for patients experiencing complications of long-term parenteral nutrition who are expected to have permanent intestinal failure, but outcomes are hindered by immunosuppression-related complications. Much of the available data comes from single center retrospective reports, with variable inclusion criteria, intestinal failure definitions, and follow-up durations; this limits the ability to analyze outcomes and identify best practices. As most children now survive long-term, the focus of management has shifted to the avoidance and management of comorbidities, support of normal growth and development, and optimization of quality of life for these medically and surgically complex patients.

Morbidity and mortality among "big" babies who develop necrotizing enterocolitis: A prospective multicenter cohort analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is classically a disease of prematurity, with less reported regarding morbidity and mortality of this disease among other infants. METHODS: Data were prospectively collected from 2009 to 2015 at 252 Vermont Oxford Network member centers on neonates with birth weight>2500g admitted to a participating NICU within 28days of birth. RESULTS: Of 1629 neonates with NEC, gestational age was 37 (36, 39) weeks, and 45% had major congenital anomalies, most commonly gastrointestinal defects (20%), congenital heart defects (18%), and chromosomal anomalies (7%). For the 23% of infants who had surgery for NEC, mortality and length of stay were 23% and 63 (36, 94) days versus 8% and 34 (22, 61) days in medical NEC. Independent predictors of mortality were congenital heart defects (p<0.0001), chromosomal abnormalities (p<0.05), other congenital malformations (p<0.001), surgical NEC (p<0.0001), and sepsis (p<0.05). All of these in addition to gastrointestinal defects were independent predictors of increased length of stay. Nutritional morbidity at discharge included 6% receiving no enteral feeds and 27% who were <10th percentile weight-for-age. CONCLUSIONS: Major congenital anomalies are present in nearly half of >2500g birth weight infants diagnosed with necrotizing enterocolitis. Morbidity and mortality increase with sepsis, surgical disease, and congenital anomalies. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level II.

Ileostomy Prolapse in Children with Intestinal Dysmotility.

BACKGROUND: A relationship between intestinal motility and ileostomy prolapse has been suggested but not demonstrated objectively. AIMS: This study evaluated the association between ileostomy prolapse and intestinal dysmotility in children. METHODS: IRB-approved retrospective review of 163 patients with ileostomies (1998-2014) at a single institution. Patients were categorized as having clinical dysmotility as a primary diagnosis (n = 33), clinically suspected dysmotility based on underlying diagnosis (n = 60), or intestinal dysmotility unlikely (n = 70) at the time of ileostomy present. Intestinal manometry was categorized as normal (n = 13) or abnormal (n = 10). Primary outcome was pathologic stoma prolapse. Multivariate analysis using a logistic regression model and log-rank test to compare stoma prolapse rates over time between motility groups were used. RESULTS: Clinical diagnosis of dysmotility (p ≤ 0.001) and manometric findings of dysmotility (p = 0.024) were independently associated with stoma prolapse. Clinical dysmotility correlated with manometric findings (κ = 0.53). Prolapse occurred in 42% of patients with dysmotility, 34% of patients with suspected dysmotility, and 24% of patients with normal motility. One-year prolapse-free stoma "survival" was 45% for dysmotility, 72% for suspected dysmotility, and 85% for intestinal dysmotility unlikely groups (p = 0.006). CONCLUSIONS: Children with intestinal dysmotility are at great risk for stoma prolapse. Intestinal manometry could help identify these patients preoperatively.

Radiographic measurement of intestinal length among children with short bowel syndrome: Retrospective determination remains problematic.

PURPOSE: Small bowel length is the most reliable predictor of enteral independence in pediatric short bowel syndrome. Retrospectively measured bowel lengths on upper GI with small bowel follow-through (UGI/SBFT) were compared to operative measurements. METHODS: A pediatric radiologist and surgical trainees blinded to operative measurements retrospectively analyzed UGI/SBFT studies using the digital radiography curved measurement tool. Children with SBS and severe intestinal failure (parenteral nutrition >90days) at a multidisciplinary intestinal failure program 2002-2015 were included. Data were expressed as median (Q1, Q3). RESULTS: Thirty-six children aged 0.8 (0.4, 3.7) years were analyzed. Fifty-six percent had intestinal malrotation, and 58% had prior serial transverse enteroplasty. Studies were conducted within 10 (7, 20) days of surgery. Intraoperative bowel length was 90cm (45, 142), while UGI/SBFT measurement by radiologist was 45cm (28, 63), with a mean difference of 47cm (SD 58cm, p<0.001) and a mean percent error of 50%. Radiographic assessment underestimated intestinal length in 83% of patients. CONCLUSION: Bowel length measured retrospectively from upper GI with small bowel follow-through studies usually underestimated intraoperative bowel length. The limits of agreement were too wide for this technique to be clinically useful. Operative measurement remains necessary to assess intestinal length and rehabilitation potential. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: Level III.

Severe neurodevelopmental disability and healthcare needs among survivors of medical and surgical necrotizing enterocolitis: A prospective cohort study.

PURPOSE: This study characterizes neurodevelopmental outcomes and healthcare needs of extremely low birth weight (ELBW) survivors of necrotizing enterocolitis (NEC) compared to ELBW infants without NEC. METHODS: Data were collected prospectively on neonates born 22-27weeks' gestation or 401-1000g at 47 Vermont Oxford Network member centers from 1999 to 2012. Detailed neurodevelopmental evaluations were conducted at 18-24months corrected age. Information regarding rehospitalizations, postdischarge surgeries, and feeding was also collected. "Severe neurodevelopmental disability" was defined as: bilateral blindness, hearing impairment requiring amplification, inability to walk 10 steps with support, cerebral palsy, and/or Bayley Mental or Psychomotor Developmental Index <70. Diagnosis of NEC required both clinical and radiographic findings. RESULTS: There were 9063 children without NEC, 417 with medical NEC, and 449 with surgical NEC evaluated. Significantly higher rates of morbidity were observed among infants with a history of NEC. Those with surgical NEC were more frequently affected across all outcome measures at 18-24months corrected age: 38% demonstrated severe neurodevelopmental disability, nearly half underwent postdischarge operations, and a quarter required tube feeding at home. CONCLUSION: At 18-24months, extremely low birth weight survivors of necrotizing enterocolitis were at markedly increased risk (p<0.001) for severe neurodevelopmental disability, postdischarge surgery, and tube feeding. LEVEL OF EVIDENCE: II (prospective cohort study with <80% follow-up rate).

Contemporary Outcomes of Infants with Gastroschisis in North America: A Multicenter Cohort Study.

OBJECTIVE: To quantify outcomes and analyze factors predictive of morbidity and mortality in infants with gastroschisis. STUDY DESIGN: Clinical data regarding neonates with gastroschisis born between 2009 and 2014 were prospectively collected at 175 North American centers. Multivariate regression was used to assess risk factors for mortality and length of stay (LOS). RESULTS: Gastroschisis was diagnosed in 4420 neonates with median birth weight 2410 g (IQR 2105-2747). Survival (discharge home or alive in hospital at 1 year) was 97.8% with a 37 day median LOS (IQR 27-59). Sepsis, defined by positive blood or cerebrospinal fluid culture, was the only significant independent predictor of mortality (P = .04). Significant independent determinants of LOS and the percentage of neonates affected were as follows: bowel resection (9.8%, P < .0001), sepsis (8.6%, P < .0001), presence of other congenital anomalies (7.6%, including 5.8% with intestinal atresias, P < .0001), necrotizing enterocolitis (4.5%, P < .0001), and small for gestational age (37.3%, P = .0006). Abdominal surgery in addition to gastroschisis repair occurred in 22.3%, with 6.4% receiving gastrostomy or jejunostomy tubes and 6.3% requiring ostomy creation. At discharge, 57.0% were less than the 10th percentile weight for age. The mode of delivery (52.4% cesarean delivery) was not associated with any differences in outcome. CONCLUSIONS: Although neonates with gastroschisis have excellent overall survival they remain at risk for death from sepsis, prolonged hospitalization, multiple abdominal operations, and malnutrition at discharge. Outcomes appear unaffected by the use of cesarean delivery. Further opportunities for quality improvement include sepsis prevention and enhanced nutritional support.

High prevalence of same-sex twins in patients with cloacal exstrophy: Support for embryological association with monozygotic twinning.

PURPOSE: Previous studies have hypothesized that cloacal exstrophy may be caused by errors early in embryological development related to monozygotic twinning. This study reports the prevalence of twins in a large cohort of patients with cloacal exstrophy. METHODS: Patients with cloacal exstrophy treated 1974-2015 were reviewed for reports of multiple gestation or conjoined twinning. The genetic sex of the patient and their twin, and any mention of anomaly in the twin were recorded. Neither placental exam nor genetic testing results were available to definitively determine zygosity. RESULTS: Of 71 patients, 10 had a live born twin (14%), all of whom were of the same genetic sex as the affected patient. One additional patient's twin suffered intrauterine fetal demise, and another patient had a conjoined heteropagus twin. None of the twins were affected by exstrophy-epispadias complex. The rate of twin birth in this cohort was 4.4-7.7 higher than that reported by the Centers for Disease Control in the general population time period (P<0.001), with a striking preponderance of same-sex pairs. CONCLUSIONS: The highly significant prevalence of same-sex twin pairs within this cohort supports the hypothesis that the embryogenesis of cloacal exstrophy may be related to errors in monozygotic twinning. LEVEL OF EVIDENCE: 2b.

Nutrient delivery in mechanically ventilated surgical patients in the pediatric critical care unit.

PURPOSE: Inadequate nutrient intake is associated with poor outcomes in critically ill children. We examined macronutrient delivery in surgical patients in the pediatric intensive care unit (PICU). METHODS: In a prospective international cohort study of mechanically ventilated children (1month to 18years), we recorded adequacy of cumulative nutrient delivery in the PICU. Surgical patients enrolled in this study were included in the current analysis. Protein intake <60% of the prescribed goal was deemed inadequate. RESULTS: Five hundred nineteen surgical patients, 45% female, median age 2years (IQR 0.5, 8), BMI z score -0.26, with 9-day median PICU stay and 60-day mortality 5.8% were enrolled. Three hundred forty-one (66%) patients received enteral nutrition (EN), and median time of initiation was PICU day 2. EN delivery was interrupted in 68% of these patients for a median duration of 9hours. Median enteral protein delivery was <15% of the prescribed goal and was <60% in two-thirds of the cohort. Patients with inadequate enteral protein delivery had longer time to EN initiation (p<0.001) and longer duration of EN interruptions (p<0.001) compared to those with adequate delivery. CONCLUSION: Enteral protein delivery in critically ill pediatric surgical patients is inadequate. Early EN initiation and minimizing interruptions may increase protein delivery and potentially improve outcomes in this population. LEVEL OF EVIDENCE: I. TYPE OF STUDY: Prospective study.

Hospital transfers and patterns of mortality in very low birth weight neonates with surgical necrotizing enterocolitis.

PURPOSE: The objectives of this study were to evaluate mortality rates in very low birth weight (VLBW) infants with surgical necrotizing enterocolitis (NEC) by level of available surgical resources and to determine the effect of hospital transfer on mortality. METHODS: Mortality among 4328 VLBW neonates with surgical NEC born 2009-2013 was assessed using the Vermont Oxford Network database. NICUs were classified by availability of resources as a marker of overall center capability: type A (restrictions on ventilation or do not routinely perform major neonatal surgery), type B (perform major neonatal surgery but not cardiac bypass), and type C (perform major surgery, including cardiac bypass in infants). RESULTS: Mortality was higher among those who had surgery at type B centers versus type C centers (44.3% vs 36.4%, adjusted prevalence ratio 1.20 (95% CI: 1.08, 1.33)). Neonates who were not transferred between birth and surgery had a higher mortality compared to those transferred (44.6% vs 31.6%, adjusted prevalence ratio 1.39 (95% CI: 1.25, 1.55)). CONCLUSION: Transfer between birth and surgery and a higher level of surgical resources at the operative center were associated with lower mortality. Early transfer of high risk neonates to centers with higher levels of surgical resources may be warranted.

Growth morbidity in patients with cloacal exstrophy: a 42-year experience.

PURPOSE: Cloacal exstrophy is associated with multiple comorbidities that affect growth. This report describes long-term growth outcomes in a large cohort of patients with cloacal exstrophy and explores associated comorbidities. METHODS: Records of 71 patients with cloacal exstrophy who were treated between 1974 and 2015 were reviewed, and 62 patients with growth data from 2 to 20years of age were included. Genetic sex, gender of rearing, and all heights, weights, and comorbidities were noted for each patient. Height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, and BMIZ) were determined using US Centers for Disease Control 2000 growth data, and average patient z-scores were calculated. RESULTS: There were 904 height and 1301 weight measurements available for 62 patients. 31 were genetically 46,XY, 21 of whom underwent gonadectomy in infancy and were raised female. 46,XX patients, 46,XY male patients, and 46,XY female patients all had median HAZ and WAZ substantially lower than the general population, with median HAZ less than -2, while maintaining normal BMIZ. Short bowel syndrome and enterocystoplasty with intestine were associated with lower z-scores for all parameters. CONCLUSIONS: Patients with cloacal exstrophy have significant multifactorial long-term growth failure. These benchmark data can be used to further optimize management. LEVEL OF EVIDENCE: 2b.

Necrotizing enterocolitis is associated with earlier achievement of enteral autonomy in children with short bowel syndrome.

PURPOSE: Necrotizing enterocolitis (NEC) remains one of the most common underlying diagnoses of short bowel syndrome (SBS) in children. The relationship between the etiology of SBS and ultimate enteral autonomy has not been well studied. This investigation sought to evaluate the rate of achievement of enteral autonomy in SBS patients with and without NEC. METHODS: Following IRB approval, 109 patients (2002-2014) at a multidisciplinary intestinal rehabilitation program were reviewed. The primary outcome evaluated was achievement of enteral autonomy (i.e. fully weaning from parenteral nutrition). Patient demographics, primary diagnosis, residual small bowel length, percent expected small bowel length, median serum citrulline level, number of abdominal operations, status of the ileocecal valve (ICV), presence of ileostomy, liver function tests, and treatment for bacterial overgrowth were recorded for each patient. RESULTS: Median age at PN onset was 0 weeks [IQR 0-0]. Median residual small bowel length was 33.5 cm [IQR 20-70]. NEC was present in 37 of 109 (33.9%) of patients. 45 patients (41%) achieved enteral autonomy after a median PN duration of 15.3 [IQR 7.2-38.4]months. Overall, 64.9% of patients with NEC achieved enteral autonomy compared to 29.2% of patients with a different primary diagnosis (p=0.001, Fig. 1). Patients with NEC remained more likely than those without NEC to achieve enteral autonomy after two (45.5% vs. 12.0%) and four (35.7% vs. 6.3%) years on PN (Fig. 1). Logistic regression analysis demonstrated the following parameters as independent predictors of enteral autonomy: diagnosis of NEC (p<0.002), median serum citrulline level (p<0.02), absence of a jejunostomy or ileostomy (p=0.013), and percent expected small bowel length (p=0.005). CONCLUSIONS: Children with SBS because of NEC have a significantly higher likelihood of fully weaning from parenteral nutrition compared to children with other causes of SBS. Additionally, patients with NEC may attain enteral autonomy even after long durations of parenteral support.

Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients.

PURPOSE: Patient selection for transplant evaluation in pediatric intestinal failure is predicated on the ability to assess long-term transplant-free survival. In light of trends toward improved survival of intestinal failure patients in recent decades, we sought to determine if the presence of biopsy-proven hepatic cirrhosis or the eventual achievement of enteral autonomy were associated with transplant-free survival. METHODS: After IRB approval, records of all pediatric intestinal failure patients (parenteral nutrition (PN) >90 days) treated at a single intestinal failure center from February 2002 to September 2014 were reviewed. Chi-squared, Mann-Whitney, and log-rank testing were performed as appropriate. RESULTS: Of 313 patients, 174 eventually weaned off PN. Liver biopsies were available in 126 patients (most common indication was intestinal failure associated liver disease, IFALD), and 23 met histologic criteria for cirrhosis. Transplant-free survival for the whole cohort of 313 patients was 94.7% at 1 year and 89.2% at 5 years. Among patients with liver biopsies, transplant-free survival in cirrhotics vs. noncirrhotics was 95.5% vs. 94.1% at one year and 95.5% vs. 86.7% at 5 years (P=0.29). Transplant-free survival in patients who achieved enteral autonomy compared with patients who remained PN dependent was 98.2% vs. 90.3% at one year and 98.2% vs. 76.9% at 5 years (P<0.001). There was no association between cirrhosis and eventual enteral autonomy (P=0.88). CONCLUSIONS: Achieving enteral autonomy was associated with improved transplant-free survival in pediatric intestinal failure patients. There was no association between histopathological diagnosis of cirrhosis and transplant-free survival in the cohort. These data suggest that automatic transplant referral may not be required for histopathological diagnosis of cirrhosis alone, and that ongoing efforts aimed at achievement of enteral autonomy remain paramount in pediatric intestinal failure.