Principal Investigator: Michael Rollins
Keywords: Lipid , Reduced Lipid , PNAC , PNALD Department: Pediatric Surgery Development
IRB Number: 00078448
Specialty: Surgery, General, Surgery, General
Sub Specialties: Abdominal Wall Reconstruction Surgery, Upper Gastrointestinal Tract Surgery
Recruitment Status: Active, not recruiting

Contact Information

Lija Mammen

Brief Summary

  1. To determine whether neonates and infants receiving parenteral nutrition (PN) with intravenous fat emulsion reduction (IFER) (1 g/kg/day) will have lower rates of rise of direct bilirubin compared to those receiving standard intravenous fat emulsion (IVFE) therapy (3 g/kg/day)
  2. To compare the time to development of parenteral nutrition-associated cholestasis (PNAC) in neonates and infants receiving PN with IFER (1 g/kg/day) compared to those receiving PN with standard IVFE administration (3 g/kg/day)
  3. To determine if IFER results in normal growth and essential fatty acid (EFA) parameters by measuring weight, length, head circumference and EFA profiles monthly during the study period.
  4. To compare neurodevelopmental outcomes (NDOs) at 12 and 24 months of age of those treated with IFER with those treated with standard IVFE doses using a combination of neurodevelopmental screening tools (e.g. Bayley Scales of Infant Development, MacArthur Communicative Development Inventory, etc.) aimed at capturing several developmental domains such as motor, cognition, speech and language, sensory, and behavior.

Inclusion Criteria

Inclusion Criteria

Study subjects will be neonates and infants who are ≥28 weeks corrected gestational age at the time of enrollment who are parenteral nutrition naïve and whose bilirubin has never been <2 mg/dL with the following diagnoses:

  1. Meconium ileus and peritonitis
  2. Gastroschisis
  3. Omphalocele >4 cm in diameter or with liver herniated outside of the abdominal cavity
  4. Necrotizing enterocolitis requiring surgical intervention (drain placement, laparotomy, bowel resection)
  5. Volvulus
  6. Intestinal atresia with >50% bowel loss as defined by bowel length nomogram (Figure 1)

Figure 1.  Nomogram estimating normal small bowel length based on height at the time of surgery.26

This population was selected because of their high risk for developing PNAC due to their underlying disease process and limited ability to tolerate enteral feeds.  Using this group of subjects will allow for sufficient data to be obtained with the fewest number of subjects over the shortest period of time.

No preference will be given to sex, race or ethnic background during the enrollment of subjects into the study.

Exclusion Criteria

Exclusion Criteria

  1. Weight <1kg

  2. A metabolic pathway defect which is associated with liver dysfunction in the neonatal period including: hereditary fructose intolerance, galactosemia due to transferase deficiency and neonatal tyrosinemia, and/or disorders of lipid metabolism

  3. Hepatic insufficiency as documented by either a biopsy with cirrhosis and/or a marked aberration in synthetic function (defined by elevated prothrombin time (INR ≥2.0) with no evidence of a systemic coagulopathy and no administration of an anticoagulant

  4. Primary or secondary liver disease as defined by an elevated prothrombin time (INR ≥2.0) and/or elevation of liver function tests greater than twice the upper limit of the age-adjusted norm (includes hepatitis)

  5. Congenital obstruction of the hepatobiliary tree (e.g. biliary atresia, choledochal cyst)

  6. History of PNAC or a direct bilirubin >2 mg/dL at any time prior to enrollment/randomization

  7. Renal failure (as defined by a creatinine >1.5 mg/dL)

  8. Use of extracorporeal membrane oxygenation (ECMO), as hemolysis from the ECMO circuit may cause a mixed hyperbilirubinemia unrelated to the development of PNAC

  9. Documented active infection which may be communicable, including infectious hepatitis or human immunodeficiency virus

  10. Previous receipt of choleretic agents (e.g. ursodiol, phenobarbital, cholecystokinin). This is done in order to avoid the use of an agent which may reduce cholestasis and the development of PNAC.

  11. Current administration of phenobarbital or other barbiturates

  12. No infant with a congenital or acquired anomaly which will require major cardiovascular surgery

  13. Major congenital or chromosomal anomaly

  14. Hypoxic ischemic encephalopathy

  15. Congenital defect of the brain

  16. Major seizure disorder