Commentary on “Lipid Emulsions for Parenterally Fed Preterm Infants”

Lipid emulsions provide essential fatty acids and lipid soluble vitamins, as well as a substantial fraction of the non-protein energy content of parenteral nutrition for supporting preterm or sick newborn infants. Traditional soybean oil-based emulsions, however, contain few medium-chain triglycerides and insufficient levels of omega-3 long-chain polyunsaturated fatty acids such as eico-sapentaenoic acid and docosahexaenoic acid to meet recommended needs. Consequently, soybean oil-based emulsions are thought to have low antioxidant capacity, and use has been associated with adverse effects attributed to oxidative stress, lipid peroxidation, and inflammation. A common clinical concern is that prolonged administration of soybean oil-based emulsions contributes to the pathogenesis of cholestatic “parenteral nutrition-associated liver disease” (PNALD) that can progress to hepatic steatosis, fibrosis, and liver failure [1].

Newer multi-component (composite) lipid emulsion formulations containing additional olive, coconut, or fish oils (a rich source of omega-3 fatty acids) have been developed to obviate these nutritional and metabolic problems [2]. A 2018 European expert group consensus guideline recommends considering the use of composite lipid emulsions (with or without fish oil) rather than soybean oil-based emulsions as the preferred option for preventing PNALD in newborn infants receiving parenteral nutrition for more than a few days [3].

The evidence base for this practice has been appraised and synthesized in the recently updated Cochrane review of randomized controlled trials of different lipid emulsions for parenterally fed preterm infants [4]. The authors identified 29 eligible trials, but these were generally small (2,037 infants participating in total), had methodological weaknesses (including incomplete assessment and selective reporting of outcome data), and some heterogeneity in the definition of PNALD.

Meta-analysis did not show an effect of composite lipid emulsion without fish oil- versus soybean oil-based emulsion on the risk of developing PNALD (either when defined as serum conjugated bilirubin >2 mg/dL or as per the primary investigators’ definition). Meta-analyses of trials of fish oil-containing emulsion versus soybean oil-based emulsion did not show an effect on PNALD (serum conjugated bilirubin >2 mg/dL). There was some evidence that use of fish oil-containing emulsions reduced the risk of PNALD (as per primary investigators’ definitions), but a sensitivity analysis excluding a trial at high risk of bias did not show an effect (Fig. 1 [5-14]).

The review did not show any evidence of an effect of fish oil-containing lipid emulsions on other outcomes, including bronchopulmonary dysplasia and retinopathy of prematurity, that might plausibly be affected by the anti-oxidative effects of omega-3 long-chain polyunsaturated fatty acids in fish oil. These findings are consistent with those of a recent large randomized controlled trial that showed that enteral supplementation with lipid emulsion-containing docosahexaenoic acid did not confer any benefits, including any effect on bronchopulmonary dysplasia, for infants born before 29 weeks’ gestation [15].

Using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods [16], the authors assessed the evidence for the effects of composite lipid emulsion (with or without fish oil) on PNALD as “low” because of risk of bias in the included trials and the imprecision of estimates of effect (95% confidence interval included harmful or beneficial effect estimates). The review concluded that given this paucity of evidence for superiority of 1 lipid emulsion versus another to prevent PNALD in preterm or sick newborn infants, there is justification for undertaking further high-quality trials to provide data of sufficient validity and applicability to inform policy and practice.

Cochrane Neonatal reviews are produced with support from Vermont Oxford Network, a worldwide collaboration of health professionals dedicated to providing evidence-based care of the highest quality for newborn infants and their families.

The authors have no conflicts of interest to declare.

National Institute of Health Research (UK) Cochrane Programme Grant (16/114/03).

All authors contributed to writing this commentary.