Newer alternative fat emulsions versus the conventional pure soybean oil based fat emulsions for intravenous nutrition in preterm infants.

Review question: Are the newer alternative fat emulsions better than the conventional pure soybean oil based fat emulsions for improving outcomes in preterm infants?

Background: Preterm infants who need nutrition through intravenous lines have been conventionally given pure soy oil based fat emulsions. High polyunsaturated fatty acid (PUFA) content in pure soy oil based emulsions can, however, be harmful to preterm infants. The newer lipid emulsions (LE) from alternative lipid sources with reduced PUFA content may improve clinical outcomes in preterm infants.

Study characteristics: Review authors searched the medical literature and identified fifteen eligible studies (including 979 infants).

Key findings: All LE in this review appeared to be safe and were well tolerated in preterm infants. This review did not find any significant differences in the clinically important outcomes of death, growth, lung disease or severe eye disease (retinopathy of prematurity ≥ stage 3) with the use of newer alternative LE compared with the conventional pure soy oil based LE.

Conclusions: Based on this review, there is insufficient evidence to recommend any of the newer alternative LE over the conventional pure soy oil based LE or vice-versa. Further studies are required to evaluate the effectiveness of newer LE compared with conventional pure soy based LE in preterm infants.

Authors' conclusions: 

All lipid emulsions in this review appeared to be safe and were well tolerated in preterm infants. Compared with the pure soy oil based LE, use of MOFS-LE was associated with a decrease in the early stages (1-2) of ROP in one study. However there were no statistically significant differences in clinically important outcomes including death, growth, BPD, sepsis, ROP ≥ stage 3, and PNALD with the use of newer alternative LE versus the conventional pure soy oil based LE (GRADE QoE ranged from ‘low’ to ‘very low’). Currently there is insufficient evidence to recommend any alternative LE over S-LE or vice versa in preterm infants.

Larger randomised studies focusing on important clinical outcomes, targeting specific ‘at risk’ population subgroups (e.g. extreme prematurity, long term PN, etc), and exploring the effect of different proportions of lipid constituents are required to evaluate the effectiveness of newer lipid emulsions compared with the conventional pure soy based LE in preterm infants.

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Background: 

The pure soybean oil based lipid emulsions (S-LE) conventionally used for parenteral nutrition (PN) in preterm infants have high polyunsaturated fatty acid (PUFA) content. The newer lipid emulsions (LE) from alternative lipid sources with reduced PUFA content may improve clinical outcomes in preterm infants.

Objectives: 

To determine the safety and efficacy of the newer alternative LE compared with the conventional S-LE for PN in preterm infants.

Search strategy: 

We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG) to search the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 7), MEDLINE (1946 to 31 July 2015), EMBASE (1947 to 31 July 2015), CINAHL (1982 to 31 July 2015), Web of Science (31 July 2015), conference proceedings, trial registries (clinicaltrials.gov, controlled-trials.com, WHO's ICTRP), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: 

Randomised or quasi-randomised controlled trials in preterm infants (< 37 weeks), comparing newer alternative LE with S-LE.

Data collection and analysis: 

Data collection and analysis conformed to the methods of the CNRG. We assessed the quality of evidence for important outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, in addition to reporting the conventional statistical significance of results.

Main results: 

Fifteen studies (N = 979 infants) are included in this review. Alternative LE including medium chain triglycerides/long chain triglycerides (MCT/LCT) LE (3 studies; n = 108), MCT-olive-fish-soy oil-LE (MOFS-LE; 7 studies; n = 469), MCT-fish-soy oil-LE (MFS-LE; 1 study; n = 60), olive-soy oil-LE (OS-LE; 7 studies; n = 406), and borage-soy oil-LE (BS-LE; 1 study; n = 34) were compared with S-LE. The different LE were also considered together to compare ‘all fish oil containing-LE’ versus S-LE (7 studies; n = 499) and ‘all alternative LE’ versus S-LE (15 studies; n = 979). Some studies had multiple intervention arms and were included in more than one comparison. No study compared pure fish oil-LE or structured-LE to S-LE.

The GRADE quality of evidence (GRADE QoE) ranged from ‘low’ to ‘very low.’ Evidence came mostly from small single centre studies, many focusing on biochemical aspects as their primary outcomes, with optimal information size not achieved for the important clinical outcomes in any comparison.

In the primary outcomes of the review there was a pooled effect towards decreased bronchopulmonary dysplasia (BPD) in OS-LE vs S-LE (4 studies, n = 261) not reaching statistical significance (typical risk ratio (RR) 0.69, 95% confidence interval (CI) 0.46 to 1.04, I² = 32%; typical risk difference (RD) -0.08, 95% CI -0.17 to 0.00, I² = 76%; GRADE QoE: ‘very low’). No difference in BPD was observed in any other comparison. There were no statistically significant differences in the primary outcomes of death, growth rate (g/kg/day) or days to regain birth weight in any comparison.

Retinopathy of prematurity (ROP) stage 1-2 was reported to be statistically significantly lower in one single centre study (n = 80) in the MOFS-LE group compared with the S-LE group (1/40 vs 12/40, respectively; RR 0.08, 95% CI 0.01 to 0.61; RD -0.27, 95% CI -0.43 to -0.12; number needed to benefit (NNTB) 4, 95% CI 2 to 8). However there were no statistically significant differences in the secondary outcome of ROP ≥ stage 3 in any of the individual studies or in any comparison (GRADE QoE: ‘low’ to ‘very low’). No other study reported on ROP stages 1 and 2 separately.

There were no statistically significant differences in the secondary outcomes of sepsis, PN associated liver disease (PNALD)/cholestasis, ventilation duration, necrotising enterocolitis (NEC) ≥ stage 2, jaundice requiring treatment, intraventricular haemorrhage grade III-IV, periventricular leukomalacia (PVL), patent ductus arteriosus (PDA), hypertriglyceridaemia, and hyperglycaemia in any comparison.

No study reported on neurodevelopmental outcomes or essential fatty acid deficiency.

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