Cholestasis and Clinical Outcomes in High-risk Neonates in Level IV NICU on Prolonged Parenteral Nutrition with Smoflipid versus Intralipid

Background: Many neonatal intensive care units (NICU) have transitioned from conventional soy-based to mixed-oil lipid emulsions, but the literature examining the impact on the incidence and severity of parenteral nutrition-associated cholestasis (PNAC) in high-risk neonates on long-term parenteral nutrition (PN) is limited. The aim of this study was to determine the association of PNAC with mixed-oil (Smoflipid) versus soybean-oil (Intralipid) lipid emulsion use in high-risk neonates on prolonged PN and the impact on clinical outcomes.

Methods: A single-center retrospective cohort study was conducted with 138 neonates admitted to a Level IV NICU between January 1st, 2013 and December 31st, 2020, who required PN for ≥4 weeks with Smoflipid 20% (N=37) or Intralipid 20% (N=101). In order to achieve comparability of treatment groups, a propensity score was built using the following variables: sex, gestational age, birth weight, intubation at birth, gastrointestinal operation in the NICU, gastroschisis, necrotizing enterocolitis, intestinal atresia, culture-positive sepsis, and bowel perforation. The independent association of lipid emulsion type with PNAC among the total sample (N=138) was analyzed using an overlap propensity score weighted logistic regression model. We utilized a 2:1 propensity score (PS) match resulting in 44 Intralipid and 22 Smoflipid babies included in the secondary analysis. Demographic characteristics and outcomes were compared between Intralipid and Smoflipid groups using Mann-Whitney U and chi-square test as appropriate before and after the PS matching.

Results: The Smoflipid group had a 37% lower odds of developing PNAC, but lipid-type did not have a significant effect on PNAC with regression analysis (OR, 0.73; CI, 0.27-1.95; p=.52)(Table 1). In the PS matching analysis, the Smoflipid group gained more weight clinically from birth to 8-9 weeks [median 1136 vs. 928 grams, p=.18] (Table 2). There was also a decreased incidence of PNAC in the Smoflipid group compared to the Intralipid group [23% vs. 34%, p=.34] (Table 2). Time to developing cholestasis was clinically shorter in the Smoflipid group [median 16 vs. 38 days, p=.22] with higher peak direct bilirubin levels [median 6.4 vs. 3.2 mg/dL; p=.15)(Table 2). Duration of cholestasis [median 90 vs. 38 days, p=.04] was longer in the Smoflipid group with statistical significance, but they had clinically shorter NICU stays [median 101 vs. 112 days, p=.10] and a reduction in mortality before discharge [0% vs. 9%, p=.30](Table 2).

Conclusion: Our study suggests that lipid emulsion type does not have a statistically significant effect on the incidence of PNAC, but Smoflipid may clinically enhance growth, shorten the length of NICU hospitalization, and reduce mortality before discharge. However, a higher severity of cholestasis was observed in the Smoflipid group even after PS matching. Further research is needed to delineate the impact of Smoflipid use for long-term PN on medically complex neonates.