Smoflipid

The first plasma pool displaying baseline triglyceride concentration of 1.67 mmol/L was spiked at fixed ratio with increasing concentrations of exogenous triglycerides (SMOFlipid 200 mg/mL; Fresenius Kabi, Verona, Italy) up to 11.35 mmol/L. The second pool displaying baseline total bilirubin concentration of 9.5 μmol/L was spiked at fixed ratio with increasing total bilirubin concentrations (Product Number B 4126; Sigma–Aldrich, Saint Louis, MO, USA) up to 658 μmol/L. The third hemolytic pool was generated by mechanical injury of red blood cells, by passing whole anticoagulated blood through a very fine needle, as described elsewhere [17 (link)]. Scalar amounts of this hemolyzed blood were then added to the non-hemolyzed pool to obtain gradually increasing values of cell-free hemoglobin in plasma, to yield a final concentration comprised between 0.03 g/L (i.e., non-hemolyzed blood) and 4.1 g/L. A detailed procedure for serum pool preparation has been previously described [18 (link)].

This is a prospective study performed within the Donna Mega trial (NCT02760472), a monocentric randomized intervention study that compared two parenteral lipid emulsions, Smoflipid (Fresenius Kabi AB, Uppsala, Sweden) and Clinoleic (Baxter Medical AB, Kista, Sweden), with the primary outcome being ROP and its relation to infant serum fatty acid levels. Infants born at GA below 28 weeks admitted to the neonatal intensive care unit at Sahlgrenska University Hospital in Gothenburg between 201304-04 and 2015-09-22 were eligible for inclusion. Exclusion criterion was any major congenital malformation. In total, 78 infants were included in the original study. Out of these, 47 infants, where sufficient serum volumes for sphingolipid analysis remained after the Donna Mega trial’s primary analyses, were included in the present study. Details of the cohort and results of primary outcomes have been previously published [10 (link),22 (link)].

Parenteral nutrition (PN): The PN was started early after birth using starter PN. Individualized PN was prescribed daily. Starter PN contains dextrose 10%, amino acids 4%, and calcium gluconate 0.01 mmol/mL. Individualized PN solution containing amino acids, glucose, minerals, trace elements, water-soluble vitamins, and fat-soluble vitamins was started within the first 24 h of life and infused continuously for 24 h.
The subjects were categorized into two groups of LE—(1) SMOFlipid (Fresenius Kabi, Melrose Park, IL, USA): infants were given parenteral multi-oil emulsions, containing soybean oil, MCT, olive oil, and fish oil; and (2) intralipid 20% medium-chain and long-chain fat injection: containing soybean oil and MCT.
The initial LE dose was 0.5 to 1.0 g per kg per day early after birth and was increased by 0.5 to 1.0 g per kg per day every 24 h with a maximum of 3.0 g to 3.5 g lipids per kg per day. Triglyceride level was not measured in the routine investigation. Minimal enteral nutrition was started as soon as possible after birth if possible. A preterm formula or expressed breast milk was administrated through an orogastric tube intermittently according to the feeding protocol, which depends on birth weight.
Preterm formula was administered when human milk was not available or sufficient.

Intravenous lipid emulsion was started at 0.5 g/kg/day on day two and was increased at a dose of 0.5 g/kg/day according to tolerance to a maximum dose of 3.5 g/kg/day. Beginning in March 2010, Lipo MCT 20% (Dong guk Pharm, Seoul, Korea) was used as the primary parenteral lipid solution. Between April 2011 and January 2013, Intralipid 20% (Fresinius Kabi, Cheshire, UK) was used. Since January 2013, SMOF lipid (Fresenius Kabi, Bad Homburg, Germany) has been used in our NICU. After 2017, Omegaven (Fresinius Kabi, Cheshire, UK) was used as rescue therapy in patients with a diagnosis of PNAC. It was administered twice a week or every other day and was taken with SMOF lipid.