Prevention of Parenteral Nutrition-Associated Cholestasis With Cyclic Parenteral Nutrition in Infants

• A secondary outcome is to determine if the incidence of PN- Associated Cholestasis is lower in infants receiving cyclic PN over 20 hours compared to infants receiving standard continuous PN over 24 hours. [ Time Frame: Incidence of cholestasis (direct bilirubin >2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) ] [ Designated as safety issue: No ]
• A secondary outcome in infants who develop PN-Associated Cholestasis is to evaluate if those receiving cyclic PN will have a shorter duration of cholestasis compared to infants receiving continuous PN. [ Time Frame: Duration of cholestasis (# of days direct bilirubin > 2mg/dL) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days) . ] [ Designated as safety issue: No ]
• A secondary outcome is to evaluate if infants receiving cyclic PN will have equivalent rates of growth compared to infants receiving continuous PN. [ Time Frame: Rate of growth (g of weight and cm of length and head circumference gained per week) during time period: Initiation to Discontinuation of PN (Defined as successfully off PN for 7days). ] [ Designated as safety issue: No ]

Hypothesis to be Tested:

Since the first description of intravenous alimentation over half a century ago, parenteral nutrition (PN) has become a common nutritional intervention for conditions characterized by inability to tolerate enteral feeds such as Short Bowel Syndrome, Chronic Intestinal Pseudoobstruction, Microvillus Inclusion Disease, Crohn's disease, multi-organ failure and prematurity. Parenteral Nutrition-Associated Liver Disease (PNALD) encompasses a spectrum of disease including cholestasis, hepatitis, steatosis and gallbladder sludge/stones which may progress to liver cirrhosis and even failure.

There is a direct correlation between duration of parenteral nutrition and development of cholestasis in infants. There is evidence in animals and humans that cycling of parental nutrition, defined as infusing nutrients over a time period shorter than 24 hours, reduces cholestasis. There is also data that premature infants with gestational age (GA) < 32 weeks and birth weight <1500g, as well as infants with congenital anomalies of the gastrointestinal tract, are among those at highest risk of developing Parenteral Nutrition-Associated Cholestasis (PNAC).

We therefore hypothesize that infants with gestational age (GA) <32 weeks and birth weight (BW) between <1500g, or with congenital anomaly of the gastrointestinal tract regardless of GA or BW, receiving PN over a period of 20 hours will have a decrease severity of PNAC, demonstrated by a lower peak direct bilirubin, compared to a similar control population receiving standard 24 hour infusion.

• Cholestasis
• Prematurity
• Gastroschisis
• Intestinal Atresia
• Necrotizing Enterocolitis

• Experimental: Cycling Parenteral Nutrition
  Infants in the intervention cycling group will receive infusion of carbohydrate/amino acids and intralipid over a 20-hour period. During the 4-hour window period, infants in this group will receive dextrose solution only at the same rate calculated for the carbohydrate/amino acid infusion.
  Intervention: Drug: Parenteral Nutrition
• No Intervention: Continuous Parenteral Nutrition
  Infants in this control group will receive infusion of carbohydrates/amino acids and intralipids continuously, over 24 hours.
  Intervention: Drug: Parenteral Nutrition

Inclusion Criteria:

1. Infants expected to need prolonged PN (receiving >75% PN on dol 7) with the following risk factors:

   1. Prematurity with gestational age (GA) <32 weeks AND birth weight <1500g. OR
   2. Congenital anomaly of the gastrointestinal tract regardless of GA or BW
2. Screening direct bilirubin prior to the initiation of parenteral nutrition <2mg/dL.

Exclusion Criteria:

1. Infants with major congenital anomalies, other than those of the gastrointestinal tract.
2. Infants with known obstruction of the hepatobiliary tract.
3. Infants with suspected congenital infection or suspected genetic/metabolic syndrome predisposing them to cholestasis based on direct bilirubin > 2mg/dL prior to instituting PN.