Clinical Trial: Reduction of Neonatal Parenteral Nutrition Associated Cholestasis Through Lipid Emulsions

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Incidence and Severity of Parenteral Nutrition Associated Cholestasis in Neonates Subjected to Major Surgery, Using Two Mixed Intravenous Lipid Emulsions

Brief Summary:

Parenteral nutrition associated cholestasis (PNAC) is a common complication of prolonged and exclusive parenteral nutrition (PN). Infants subjected to major surgery are often unable to receive enteral nutrition for a long period of time, during which they require exclusive PN. In preterm infants, hepatic immaturity is a predisposing factor. Intravenous lipid emulsions (ILE) used in PN may promote PNAC or protect against it depending on their composition. Medium chain triglycerides (MCT) may have a hepatic protective effect. Long chain triglycerides (LCT) of n-3 family may protect from PNAC. In several new-generation emulsions, the α-tocopherol content is higher than the gamma-tocopherol content, acting as an antioxidant, preventing lipid peroxidation.

The incidence and severity of PNAC in term and near-term infants subjected to corrective surgery for congenital abnormalities and needing prolonged PN using the ILE SMOFlipid® or Lipofundin® is compared. The investigators hypothesise that SMOFlipid® is more protective from PNAC than Lipofundin®.

Single-center, randomized, controlled and double-blinded trial on consecutive neonates admitted in the NICU, with gestational age of 34 weeks or over, undergoing corrective surgery of congenital anomaly of the digestive tract or indirectly affecting the digestive tract. Recruitment if PN with ILE was started within the first 48 hours after birth. Minimum intervention: exclusive PN for at least 1 week.

Main outcome: incidence of cholestasis (conjugated serum bilirubin >1 mg/dl [34 mmol/L]). Severity of cholestasis evaluated by the magnitude of the serum conjugated bilirubin and serum γ-glutamyltranspeptidase (GGT). Mixed effects regression models are used to take into account the correlation structure be

Detailed Summary:

BACKGROUND. Parenteral nutrition associated cholestasis (PNAC) is a common complication of prolonged and exclusive parenteral nutrition (PN). PNAC in neonates and infants is multifactorial, including the underlying pathology and the effect of certain PN nutrients. In preterm infants, hepatic immaturity is itself, a predisposing factor. Infants subjected to major surgery are often unable to receive enteral nutrition for a long period of time, during which they require exclusive PN. After that, enteral nutrition is slowly introduced alongside with the reduction of the PN. In major surgery for congenital malformations of the digestive tract, additional risk factors for PNAC are the absence of enteral nutrition, intestinal bacterial translocation and sepsis. Jejunal atresia and gastroschisis are independent risk factors for PNAC. In short bowel syndrome, changes in the bile acids enterohepatic cycle may also contribute to PNAC.

Intravenous lipid emulsions (ILE) used in PN may promote PNAC or protect against it depending on their composition. Phytosterols contained in ILE have been implicated in PNAC in newborns by disrupting bile-acid homeostasis. High intakes of soy-based fatty acids (FA) n-6 from ILE, especially palmitate, may contribute to PNAC since these are precursors of arachidonic acid, a pro-inflammatory mediator.

Medium chain triglycerides (MCT) may have a hepatic protective effect. Hence, ILE containing relatively high amounts of MCT, such as Lipofundin® (B. Braun) theoretically might be advantageous in protecting against PNAC. Long chain triglycerides (LCT) of n-3 family may protect from PNAC thorough its anti-inflammatory activity. The Omegaven® (Fresenius Kabi), exclusively based on LCT n-3 has proved to prevent and reverse PNAC in neonates.

In several n
Sponsor: Centro Hospitalar de Lisboa Central

Current Primary Outcome: Incidence of cholestasis [ Time Frame: From recruitment to full enteral feeding per mouth (up to 90 postnatal days) ]

Conjugated serum bilirubin >1 mg/dl (34 mmol/L) (Moyer, 2004).


Original Primary Outcome: Same as current

Current Secondary Outcome: Severity of cholestasis [ Time Frame: From recruitment to full enteral feeding per mouth (up to 90 postnatal days) ]

The severity of cholestasis was evaluated by the magnitude of the serum conjugated bilirubin and serum γ-glutamyltranspeptidase (GGT).


Original Secondary Outcome: Same as current

Information By: Centro Hospitalar de Lisboa Central

Dates:
Date Received: November 30, 2015
Date Started: August 2011
Date Completion: August 2016
Last Updated: July 26, 2016
Last Verified: April 2016