Rayyan M, Devlieger H, JochumF, Allegaert K. Short-term use of parenteral nutrition with a lipid
emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil : A
randomized double-blind study in preterm infants. J Parenter Enteral Nutr. 2012 36: 81S-95S.
When enteral feeding is not tolerated or insufficient, intravenous lipid emulsions are a crucial
part of parenteral nutrition (PN) support in premature neonates. Overwhelming evidence demonstrates
that healthy fatty acids during the neonatal period is critical in developing normal growth, visual and
cognitive development. However, common soybean-based emulsions contain high amounts of
linoleic acid (LA) relative to α-linolenic acid (α-LNA), low levels of arachidonic acid (AA) and no longchain polyunsaturated fatty acids (LC-PUFAs). These LC-PUFAs, such as EPA and DHA, have proven to
play an important role during brain and retinal development in preterm infants. Enteral feeding studies
have demonstrated that DHA and AA to improve growth, mental, psychomotor, and visual development.
Thus there has been a long recognized need for developing a more appropriate lipid emulsions in
pediatric and neonatal care.
Researchers in this present study hypothesized that a test lipid emulsion with medium-chain
triglycerides (MCTs), soybean, olive, and fish oils would be as safe and well tolerated as a conventional
soybean emulsion in addition to improving the fatty acid profile. Subjects were monitored in regard to
triglyceride levels, adverse events (AE), tolerability, and vital signs. In addition, researchers proposed to
prove that the test lipid emulsion is equally efficient in neonate’s growth while improving the fatty acid
profile. The test emulsion being investigated contains 4 lipids: soybean oil providing LA and α-LNA for
essential fatty acid supply, olive oil rich in monounsaturated fatty acids (MUFAs), medium-chain
triglycerides (MCTs), and fish oil for the supply of LC-PUFA.
This prospective, double-blind, randomized, parallel, controlled study examined 53 neonates,
<34 weeks’ gestation, age <34 weeks and birth weights 500-2000 g. Extremely immature neonates or
Those with severe abnormalities were excluded. Babies received PN for 7-14 days containing either an
emulsion of MCTs, soybean, olive, and fish oils (test group; n = 26) or a soybean oil emulsion (control;
n=27). Lipid dosages were: 1 g/kg body weight (BW)/d on days 1–3, 2 g/kg BW/d on day 4, 3 g/kg BW/d
on day 5, and 3.5 g/kg BW/d on days 6–14. Clinical assessments (heart rate, temperature, blood
pressure, body weight, oxygen therapy) were performed daily. Body height was assessed at birth and
after treatments. During baseline, day 5, 8, and 15- blood samples were drawn for triglycerides, HDL,
LDL, electrolytes, glucose, and liver enzymes. All laboratory assessments were assessed using
established validated standard techniques. The results for test emulsion vs. control, mean ± SD: baseline
triglyceride concentrations were 0.52 ± 0.16 vs. 0.54 ± 0.19 mmol/L and increased similarly in both
groups to 0.69 ± 0.38 vs. 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). The test group showed
a significantly lower bilirubin from baseline, compared with the control group (total bilirubin: –50.3 ±
45.8 vs. –18.6 ± 54.2μmol/L corresponding to –2.94 ± 2.68 vs. –1.09 ± 3.17mg/dL ; P < .05 between
groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid
were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs. control). This study’s
research of a lipid emulsion mixture containing MCTs, soybean, olive, and fish oils, claims to be safe and
well tolerated by preterm infants while improving the fatty acid profile.
I find the world of feeding premature infants fascinating. Little amount of nutrition support
formula makes a significant change in their delicate bodies in this critical time period. Thus it is
important to find the most appropriate nutritional formula for proper neonatal growth and
development. This study does a good job at researching a mixture lipid emulsion and attempting to
understand safety and tolerance. The tolerability was similar between the two study treatments and
was rated “very good” or “good”. However 4 infants (2 in each treatment group) experienced serious
adverse events leading to discontinue the study medication. Two infants died during the treatment
phase, and another death “possibly” related to the study drug. To me, this is inconsistent with “very
good” tolerance and too big of a health risk for any child. Premature infants are at higher risk for PNassociated hypertriglyceridemia than term infants. Infants in the test group were slightly more immature
than control infants which may have influenced the tolerance to parenteral lipids based on equal
treatments. The significant increase in LDL cholesterol in the test group is not well understood, however
the LDL/HDL ratios are consistent with breastfed preterm infants. Secondary results are promising with
decreased bilirubin in the test group and increased levels in the control group. But later the authors
explain that this is common in this patient population. This study needs to be extended for a longer
period of time (with more participants) in order to see more meaningful liver enzyme changes. Since
none of the babies required PN beyond 3 weeks, it would be unethical to keep them on it. Another
limitation is that 30% of fat intake was supplemented by EN, which may bias results. I would improve
the study by dispersing the genders equally between the 2 groups (females in test group was almost
70%), since females preterm neonates typically have more favorable clinical outcomes. This paper
references 67 influential sources, but additional research must be done regarding this topic.

RD’s should be cautious to use this information as supportive evidence until further
longer studies on larger populations are completed to confirm the safety of neonates
and efficacy of this new and innovative lipid emulsion, and its effect on mental and
visual development.

In order to maximize the benefits of lipids and minimize their adverse effects during TPN
administration, clinicians should keep in mind general guidelines:
o provide sufficient lipids to prevent essential fatty acid deficiency
o monitor lipid intolerance
o adjust lipid dose based on clinical status