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Review
. 2015 Dec 2;2015(12):CD009172.
doi: 10.1002/14651858.CD009172.pub2.

Alternative lipid emulsions versus pure soy oil based lipid emulsions for parenterally fed preterm infants

Vishal Kapoor  1 , Rebecca Glover, Manoj N Malviya
Affiliations
Review

Alternative lipid emulsions versus pure soy oil based lipid emulsions for parenterally fed preterm infants

Vishal Kapoor et al. Cochrane Database Syst Rev. .

Abstract

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 methods: 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.

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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Conflict of interest statement

None.

Figures

1
1
PRISMA flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Forest plot of comparison: MOFS‐LE versus S‐LE, outcome: 1.2 Days to regain birth weight.
4
4
Forest plot of comparison: OS‐LE versus S‐LE, outcome: 3.6 Duration of ventilation (days).
5
5
Forest plot of comparison: All alternative LE vs S‐LE, outcome: 9.9 Any sepsis (clinical and/or culture positive).
1.1
1.1. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 1: Death before discharge
1.2
1.2. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 2: Days to regain birth weight
1.3
1.3. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 3: Rate of weight gain (g/kg/day)
1.4
1.4. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 4: Bronchopulmonary dysplasia/chronic lung disease
1.5
1.5. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 5: Duration of ventilation (days)
1.6
1.6. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 6: Duration of supplemental oxygen (days)
1.7
1.7. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 7: Culture positive sepsis
1.8
1.8. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 8: Any sepsis (clinical and/or culture positive)
1.9
1.9. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 9: Necrotising enterocolitis (≥ stage 2)
1.10
1.10. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 10: Duration of phototherapy (days)
1.11
1.11. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 11: Retinopathy of prematurity (≥ stage 3 )
1.12
1.12. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 12: Intraventricular haemorrhage (grade III‐IV)
1.13
1.13. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 13: Periventricular leukomalacia
1.14
1.14. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 14: Any patent ductus arteriosus
1.15
1.15. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 15: Significant patent ductus arteriosus requiring treatment
1.16
1.16. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 16: Parenteral nutrition associated liver disease/cholestasis
1.17
1.17. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 17: Hypertriglyceridaemia
1.18
1.18. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 18: Hyperglycaemia
1.19
1.19. Analysis
Comparison 1: MOFS‐LE versus S‐LE, Outcome 19: Hypoglycaemia
2.1
2.1. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 1: Death before discharge
2.2
2.2. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 2: Days to regain birth weight
2.3
2.3. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 3: Rate of weight gain (g/kg/day)
2.4
2.4. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 4: Bronchopulmonary dysplasia/chronic lung disease
2.5
2.5. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 5: Any sepsis (clinical and/or culture positive)
2.6
2.6. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 6: Necrotising enterocolitis (≥ stage 2)
2.7
2.7. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 7: Any patent ductus arteriosus
2.8
2.8. Analysis
Comparison 2: MFS‐LE versus S‐LE, Outcome 8: Parenteral nutrition associated liver disease/cholestasis
3.1
3.1. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 1: Death before discharge
3.2
3.2. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 2: Days to regain birth weight
3.3
3.3. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 3: Rate of weight gain (g/kg/day)
3.4
3.4. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 4: Bronchopulmonary dysplasia/chronic lung disease
3.5
3.5. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 5: Bronchopulmonary dysplasia/chronic lung disease (sensitivity analysis)
3.6
3.6. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 6: Duration of ventilation (days)
3.7
3.7. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 7: Duration of supplemental oxygen (days)
3.8
3.8. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 8: Need for home oxygen therapy
3.9
3.9. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 9: Culture positive sepsis
3.10
3.10. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 10: Any sepsis (clinical and/or culture positive)
3.11
3.11. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 11: Necrotising enterocolitis (≥ stage 2)
3.12
3.12. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 12: Significant jaundice requiring treatment
3.13
3.13. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 13: Duration of phototherapy (days)
3.14
3.14. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 14: Intraventricular haemorrhage (grade III‐IV)
3.15
3.15. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 15: Periventricular leukomalacia
3.16
3.16. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 16: Any patent ductus arteriosus
3.17
3.17. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 17: Air leaks
3.18
3.18. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 18: Parenteral nutrition associated liver disease/cholestasis
3.19
3.19. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 19: Hypertriglyceridaemia
3.20
3.20. Analysis
Comparison 3: OS‐LE versus S‐LE, Outcome 20: Hyperglycaemia
4.1
4.1. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 1: Death before discharge
4.2
4.2. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 2: Days to regain birth weight
4.3
4.3. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 3: Rate of weight gain (g/kg/day)
4.4
4.4. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 4: Bronchopulmonary dysplasia/chronic lung disease
4.5
4.5. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 5: Any sepsis (clinical and/or culture positive)
4.6
4.6. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 6: Necrotising enterocolitis (≥ stage 2)
4.7
4.7. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 7: Any patent ductus arteriosus
4.8
4.8. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 8: Parenteral nutrition associated liver disease/cholestasis
4.9
4.9. Analysis
Comparison 4: MS‐LE versus S‐LE, Outcome 9: Hypertriglyceridaemia
8.1
8.1. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 1: Death before discharge
8.2
8.2. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 2: Days to regain birth weight
8.3
8.3. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 3: Rate of weight gain (g/kg/day)
8.4
8.4. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 4: Bronchopulmonary dysplasia/chronic lung disease
8.5
8.5. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 5: Duration of ventilation (days)
8.6
8.6. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 6: Duration of supplemental oxygen (days)
8.7
8.7. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 7: Culture positive sepsis
8.8
8.8. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 8: Any sepsis (clinical and/or culture positive)
8.9
8.9. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 9: Necrotising enterocolitis (≥ stage 2)
8.10
8.10. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 10: Duration of phototherapy (days)
8.11
8.11. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 11: Retinopathy of prematurity (≥ stage 3)
8.12
8.12. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 12: Intraventricular haemorrhage (grade III‐IV)
8.13
8.13. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 13: Periventricular leukomalacia
8.14
8.14. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 14: Any patent ductus arteriosus
8.15
8.15. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 15: Significant patent ductus arteriosus requiring treatment
8.16
8.16. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 16: Parenteral nutrition associated liver disease/cholestasis
8.17
8.17. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 17: Hypertriglyceridaemia
8.18
8.18. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 18: Hyperglycaemia
8.19
8.19. Analysis
Comparison 8: All fish oil containing LE versus S‐LE, Outcome 19: Hypoglycaemia
9.1
9.1. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 1: Death before discharge
9.2
9.2. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 2: Days to regain birth weight
9.3
9.3. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 3: Rate of weight gain (g/kg/day)
9.4
9.4. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 4: Bronchopulmonary dysplasia/chronic lung disease
9.5
9.5. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 5: Duration of ventilation (days)
9.6
9.6. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 6: Duration of supplemental oxygen (days)
9.7
9.7. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 7: Need for home oxygen therapy
9.8
9.8. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 8: Culture positive sepsis
9.9
9.9. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 9: Any sepsis (clinical and/or culture positive)
9.10
9.10. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 10: Necrotising enterocolitis (≥ stage 2)
9.11
9.11. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 11: Significant jaundice requiring treatment
9.12
9.12. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 12: Duration of phototherapy (days)
9.13
9.13. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 13: Retinopathy of prematurity (≥ stage 3)
9.14
9.14. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 14: Intraventricular haemorrhage (grade III‐IV)
9.15
9.15. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 15: Periventricular leukomalacia
9.16
9.16. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 16: Any patent ductus arteriosus
9.17
9.17. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 17: Significant patent ductus arteriosus requiring treatment
9.18
9.18. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 18: Air leaks
9.19
9.19. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 19: Parenteral nutrition associated liver disease/cholestasis
9.20
9.20. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 20: Hypertriglyceridaemia
9.21
9.21. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 21: Hyperglycaemia
9.22
9.22. Analysis
Comparison 9: All alternative LE versus S‐LE, Outcome 22: Hypoglycaemia
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References

References to studies included in this review

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