Parenteral nutrition-associated cholestasis and triglyceridemia in surgical term and near-term neonates: A pilot randomized controlled trial of two mixed intravenous lipid emulsions

Abstract

s u m m a r yBackground: Cholestasis is a common complication in infants receiving prolonged parenteral nutrition (PN). We studied the effects of two intravenous lipid emulsions composed with either 30% soybean oil, 30% medium-chain triglycerides (MCT), 25% olive oil, and 15% fish oil (SMOF) or with 50% MCT and 50% soybean oil n-6 (MCT/SOY) on the incidence of cholestasis in surgical term and near-term neonates. Methods: A single-center, double-blinded, randomized controlled trial compared the incidence of cholestasis using either SMOF or MCT/SOY in neonates born at gestational age !34 weeks undergoing major surgery. The primary outcome was the incidence of conjugated serum bilirubin >1 mg/dL. Other liver enzymes were assessed as secondary outcomes. A post-hoc analysis assessed serum triglycerides levels. Odds ratios were estimated by mixed-effects regression models. Results: Enrollment was prematurely interrupted because the MCT/SOY became unavailable, thus 49 infants (SMOF 22, MCT/SOY 27) completed the study. The exposure (time on PN, cumulative dose of lipids) was similar in both groups. Similar cumulative incidence rates were found for elevated conjugated bilirubinemia and other liver enzymes. Hypertriglyceridemia >250 mg/dL (12/49) was more frequent in MCT/SOY (37.0%, 95% CI 21.53e55.77) than in SMOF (9.1%, 95% CI 2.53e27.81, p ¼ 0.024). Triglyceridemia at the first assessment (median 8 postnatal days) was significantly higher with MCT/SOY than with SMOF (181 vs. 134 mg/dL, p ¼ 0.006). Over the whole study period, mean triglyceride concentration was 36.5 mg/dL higher with MCT/SOY compared with SMOF (p ¼ 0.013). Conclusion: Both emulsions had similar effects on the incidence of cholestasis and markers of liver integrity, but MCT/SOY induced higher serum triglyceride concentrations. Trial registration: ClinicalTrials.gov, NCT02633384

A Comparison of Smoflipid® and Intralipid® in the Early Management of Infants with Intestinal Failure

“…Literature evaluating the role of ILEs in the prevention of cholestasis specifically in IF patients is limited and somewhat conflicting. In a recent randomized controlled trial, neonates receiving SMOF after gastrointestinal surgery did not have higher liver enzymes or incidence of cholestasis than neonates receiving a 50% soybean based emulsion [17]. Alternatively, in a randomized controlled trial of infants in China following intestinal surgery, infants receiving SMOF for 4 weeks had lower liver enzymes and direct bilirubin but no difference in weight gain or sepsis episodes compared to patients receiving a mediumchain triglyceride/long-chain triglyceride emulsion [18].…”

Fish Oil Monotherapy for Intestinal Failure-Associated Liver Disease on SMOFlipid in the Neonatal Intensive Care Unit

“…However, the added benefit of a reduction in cholestasis with FO in the PN regimen does not completely preclude the occurrence of IFALD. In fact, it has been documented that IFALD does occur, albeit less frequently, while using combination LEs such as SMOF [14,15]. In a previous study, we reported the incidence of IFALD to be 11.2% (28/251) among pediatric patients receiving PN containing SMOF for periods longer than 30 days and 12.3% in neonates [5].…”

Nutritional Assessment in Preterm Infants: A Practical Approach in the NICU

“…In stable growing infants receiving enteral nutrition, laboratory monitoring every week or every other week is sufficient [17]. In those receiving prolonged parenteral nutrition, liver function should be monitored using serum levels of direct bilirubin, aspartate amino transferase, alanine amino transferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and triglycerides [17,84,85].…”