Pure soybean oil-based lipid emulsions (S-LE) have been used commercially worldwide, and consist of long-chain fatty acids with omega 3 to omega 6 ratio of 1:5.5 [4]. These fatty acids play an important role in several physiological processes such as immune and inflammatory response, platelet functions and early neural and visual development [5]. However, there are several studies suggesting that S-LE could have hazards due to excess linoleic acid and polyunsaturated fatty acids [6]. MOFS (MCT-olive-fish-soy oil) lipid emulsions (MOFS-LE) are mixtures of 30% medium chain triglycerides (MCT), 25% olive oil, 15% fish oil, and 30% soybean oil, and are supposed to have better immune-modulatory and anti-inflammatory properties [3].

Quite a few studies comparing efficacy and safety of S-LE and MOFS-LE in neonates exist but there is no consensus on the ideal LE [3]. The present study was designed to compare short-term effects of S-LE and MOFS-LE on soluble adhesion markers of sepsis and growth in preterm infants.

This randomized controlled double-blind pilot trial was conducted in a university-affiliated neonatal care unit (NCU) of Mansoura (Egypt) from February 2016 to February 2017. The study was approved by Medical Research Ethical Committee of Medical Faculty of Mansoura University.

Preterm neonates with possible sepsis who had positive isolates on blood culture were considered eligible for inclusion. Neonates with major congenital malformations, inborn errors of metabolism, hypoxic-ischemic encephalopathy and congenital infections were excluded. Neonates were enrolled after obtaining written informed consent from their legal guardians.

A fixed block randomization (4 per block) was used to generate the sequence. Opaque sealed envelopes were used for allocation concealment. The study medications were dispensed in identical appearing coded bottles from the outpatient department pharmacy. Participants and care providers were all blinded to the intervention. The randomization sequence and the key to the code on the medication bottles were kept with a researcher who was not involved in patient enrolment, medication administration or measuring outcomes. Patients were randomized to receive parenteral nutrition containing MOFS-LE or S-LE (Smoflipid, 20% Intralipid respectively, Fresenius Kabi, Uppsala, Sweden) for 7 days. PN was prepared aseptically by a special NCU nurse. The initial dose of LE was 0.5 g/kg/day on first day of PN, increased to a maximum of 3.5 g/kg/day. When serum triglyceride level exceeded 250 mg/dL, the lipid dosage was reduced by 25%. Amino acids, carbo-hydrates, trace elements, vitamins and electrolytes were prescribed in both groups. Neonates with early-onset sepsis received ampicillin and gentamicin while those with late-onset sepsis received flucloxacillin with either cefotaxime or gentamicin.

In all neonates, descriptive clinical data were collected at enrollment and growth data till 7 days post-randomization. Laboratory workup included complete blood count (CBC), C-reactive protein (CRP), blood culture using BACTEC 9120 culture system, serum creatinine, serum triglyceride, and blood glucose. Soluble intercellular adhesion molecule 1 (sICAM-1) and leukocyte integrin ß2 were measured by ELISA.

Statistical analysis: Chi-square and Fisher exact tests were used for categorical variables. Between-groups comparisons were done using Mann–Whitney and Student’s t-tests. Within-group comparisons were done by Wilcoxon and paired t-tests. An intention to treat analysis was done. SPSS version 22 was used for statistical analyses.

Ninety preterm infants were assessed for eligibility; 50 were excluded and 40 infants with sepsis were included (Fig. 1). Both groups were comparable for baseline characteristics (Table I). They were also comparable for the hematological parameters and CRP. Klebsiella was the commonest organism followed by Staphylococcus aureus and E. coli (n=12, 2 and 2, respectively in MOFS-LE group; and n=9, 7 and 2, respectively in S-LE group). Group B streptococcus and candida were isolated in two patients each in MOFS-LE group; and pseudomonas was isolated in two patients of S-LE group.

Fig. 1. CONSORT flow diagram of the trial.

TABLE I Baseline Characteristics of Study Groups

TABLE II Outcome Variables Between the Groups

Body weight did not differ significantly between groups while it increased in both groups similarly before and after the intervention. This observation is similar to that noted by Uthaya, et al. [11]. However, others have reported better weight gain with S-LE [3]. Length increments were not significantly different but was expected to be better with MOFS-LE due to fish oil component of MOFS-LE, being rich in docosahexaenoic acid [12].

The limitations of the study are that it was a single-center study with a small sample size. Moreover, the evaluation was done for a very short time period.

We conclude that MOFS lipid emulsions may result in higher levels of soluble adhesion molecules, which could potentially impact outcome in preterm septic neonates. Larger adequately powered studies would be needed to study the clinical and functional significance of these effects.

Contributors: MA: acquisition of clinical data, drafting the manuscript. YW: analysis and interpretation of data, revising the article draft critically for important intellectual content. BS: conception and design of the study, analysis and interpretation of the clinical data, and drafting the article. AM: acquisition of laboratory data, analysis and interpretation of the clinical data, and drafting the article. All author approved the final version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding: None; Competing Interest: None stated.