Please select the eligibility criteria that correspond to the clinical trial below.
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 between measures in time. Crude and adjusted odds-ratios with corresponding 95% confidence intervals are calculated.


Options:
A: Inclusion Criteria:

* Birth weight ≤ 1000 Gram
* Admission to the neonatal ward in the first 24 hours of life
* Informed consent and randomization in the first 5 days of life

Exclusion Criteria:

* Triplets or higher
* Conjugated bilirubin \> 1.5 mg/dl before inclusion to the study
* Conditions associated with cholestasis independent of parenteral nutrition, i.e. inborn errors of metabolism, viral infections (cytomegaly virus, HIV, Hep B, Hep C), immune mediated hemolytic disease (Rhesus incompatibility), cystic fibrosis and any other primary cholestatic disease
* Congenital neurological malformations for secondary outcome
B: Inclusion Criteria:

1. ≤ 24 months of age at enrollment
2. Evidence of early hepatic dysfunction

   * Serum conjugated bilirubin ≥ 17 umol/L on 2 consecutive readings 7 days apart

     * No evidence of sepsis

       * Normal Temperature (T between 35.5C and 38.0C)
       * Normal leukocyte count
       * Normal platelet count
       * No systemic septic symptoms
     * No prior administration of Omegaven
3. ≥ 40% of total calories administered by PN
4. Meet one of the following diagnostic categories

   * Short Bowel Syndrome

     * Abdominal surgical procedure including gastroschisis closure by any means and percutaneous drainage procedures within the past 6 months and has been receiving PN since surgery
   * Intestinal Failure

     * One of the following diagnoses for which the child is dependent on PN

       * Gastrointestinal Motility Disorder
       * Mucosal Enteropathy
5. Expectation of the treating physician that the patient will require PN for at least 3 weeks following enrollment.
6. Parents willing to participate including randomization

Exclusion Criteria:

1. Sepsis or Hemodynamic Instability of any cause.
2. Coagulopathy (Platelets ≤ 150 000, or INR ≥ 1.4)
3. Hypersensitivity to fish-, egg- or soy protein or to any of the active substances or excipients
4. Current enrollment in another clinical trial involving a surgical or pharmacologic intervention
5. Serum conjugated bilirubin \> 50 umol/L
6. Hyperlipidaemia (any of)

   * LDL ≥ 4 mmol/L
   * HDL ≥ 2 mmol/L
   * Total cholesterol ≥ 5 mmol/L
   * Triglycerides ≥ 1.5 mmol/L
7. Treatment with intravenous N-Acetylcysteine or Ursodeoxycholic acid
8. Renal insufficiency

   * Creatinine ≥ 80 umol/L
9. Disorders of Fluid Balance (any of)

   * Serum Sodium \< 130 mmol/L
   * Serum Sodium \> 145 mmol/L
10. Unstable conditions

    * Acute pulmonary edema
    * Decompensated cardiac insufficiency
    * Severe post-traumatic conditions
    * Uncompensated diabetes mellitus
    * Acute myocardial infarction
    * Stroke within 3 months
    * Thromboembolic event within 3 months
    * Metabolic acidosis

      * Serum Bicarbonate \< 17 mmol/L
C: Inclusion Criteria:

* neonates admitted in the NICU,
* gestational age of 34 weeks or over,
* undergoing corrective surgery of congenital anomaly of the digestive tract or indirectly affecting the digestive tract (eg, diaphragmatic hernia)
* initiation of PN with ILE within the first 48 hours after birth.

Exclusion Criteria:

* pre-natal or early neonatal (within the first 72 hours after birth) diagnoses of congenital or acquired hepato-biliary disease, such as biliary atresia, choledochal cyst, inborn errors of metabolism, intra-hepatic familial cholestasis, infectious hepatitis, neonatal idiopathic hepatitis, biliary lithiasis and abnormalities of liver function tests .
* later neonatal diagnoses of any above mentioned pathology.
* other congenital conditions affecting the liver function, such as meconium ileus associated with cystic fibrosis.
* treatment with ursodeoxycholic acid,
* interruption of PN for more than 48 hours for any reason, except for the postsurgical period after corrective surgery of the main condition,
* transference to another unit before completing 7 days of PN.
D: Inclusion Criteria:

* Infants of both genders
* Hospitalized
* The parent of the infant agreed to participate by signing an informed consent form
* Infants admitted hospital within 72 hours after birth(gestational age\<37 weeks)
* Birth weight \<= 2000g
* No PN support contraindications
* Parenteral nutrition for 14 days or more
* The parent of the infant is to sign an informed consent form prior to enrollment

Exclusion Criteria:

* Receiving PN before screening
* EN caloric\>10%
* Obstruction jaundice
* Suspected or identified biliary tract atresia
* Neonatal hepatitis
* Infants with liver markers \>2 times normal levels
* Infants with renal markers \>2 times normal levels
* Congenital metabolic situations
* Identified as having major chromosomal disease
* CMV, virus hepatitis and syphilis infection
* Congenital or acquired immune deficiency

Answer: C