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Meta-Analysis
. 2016 Dec 20;12(12):CD000375.
doi: 10.1002/14651858.CD000375.pub5.

Longchain polyunsaturated fatty acid supplementation in preterm infants

Kwi Moon  1 , Shripada C Rao  2 , Sven M Schulzke  3 , Sanjay K Patole  4 , Karen Simmer  5
Affiliations
Meta-Analysis

Longchain polyunsaturated fatty acid supplementation in preterm infants

Kwi Moon et al. Cochrane Database Syst Rev. .

Abstract

Background: Controversy exists over whether longchain polyunsaturated fatty acids (LCPUFA) are essential nutrients for preterm infants because they may not be able to synthesise sufficient amounts of LCPUFA to meet the needs of the developing brain and retina.

Objectives: To assess whether supplementation of formula milk with LCPUFA is safe and of benefit to preterm infants. The main areas of interest were the effects of supplementation on the visual function, development and growth of preterm infants.

Search methods: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) in the Cochrane Library (searched 28 February 2016), MEDLINE Ovid (1966 to 28 February 2016), Embase Ovid (1980 to 28 February 2016), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1980 to 28 February 2016), MEDLINE In Process & Other Non-indexed Citations (1966 to 28 February 2016) and by checking reference lists of articles and conference proceedings. We also searched ClinicalTrials.gov (13 April 2016). No language restrictions were applied.

Selection criteria: All randomised trials evaluating the effect of LCPUFA-supplemented formula in enterally-fed preterm infants (compared with standard formula) on visual development, neurodevelopment and physical growth. Trials reporting only biochemical outcomes were not included.

Data collection and analysis: All authors assessed eligibility and trial quality, two authors extracted data separately. Study authors were contacted for additional information.

Main results: Seventeen trials involving 2260 preterm infants were included in the review. The risk of bias varied across the included trials with 10 studies having low risk of bias in a majority of the domains. The median gestational age (GA) in the included trials was 30 weeks and median birth weight (BW) was 1300 g. The median concentration of docosahexaenoic acid (DHA) was 0.33% (range: 0.15% to 1%) and arachidonic acid (AA) 0.37% (range: 0.02% to 0.84%). Visual acuity Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by visual evoked potential (VEP) in six studies and by electroretinogram (ERG) in two studies. Most studies found no significant differences in visual acuity between supplemented and control infants. The form of data presentation and the varying assessment methods precluded the use of meta-analysis. A GRADE analysis for this outcome indicated that the overall quality of evidence was low. Neurodevelopment Three out of seven studies reported some benefit of LCPUFA on neurodevelopment at different postnatal ages. Meta-analysis of four studies evaluating Bayley Scales of Infant Development at 12 months (N = 364) showed no significant effect of supplementation (Mental Development Index (MDI): MD 0.96, 95% CI -1.42 to 3.34; P = 0.43; I² = 71% - Psychomotor DeveIopment Index (PDI): MD 0.23, 95% CI -2.77 to 3.22; P = 0.88; I² = 81%). Furthermore, three studies at 18 months (N = 494) also revealed no significant effect of LCPUFA on neurodevelopment (MDI: MD 2.40, 95% CI -0.33 to 5.12; P = 0.08; I² = 0% - PDI: MD 0.74, 95% CI -1.90 to 3.37; P = 0.58; I² = 54%). A GRADE analysis for these outcomes indicated that the overall quality of evidence was low. Physical growth Four out of 15 studies reported benefits of LCPUFA on growth of supplemented infants at different postmenstrual ages (PMAs), whereas two trials suggested that LCPUFA-supplemented infants grow less well. One trial reported mild reductions in length and weight z scores at 18 months. Meta-analysis of five studies (N = 297) showed increased weight and length at two months post-term in supplemented infants (Weight: MD 0.21, 95% CI 0.08 to 0.33; P = 0.0010; I² = 69% - Length: MD 0.47, 95% CI 0.00 to 0.94; P = 0.05; I² = 0%). Meta-analysis of four studies at a corrected age of 12 months (N = 271) showed no significant effect of supplementation on growth outcomes (Weight: MD -0.10, 95% CI -0.31 to 0.12; P = 0.34; I² = 65% - Length: MD 0.25; 95% CI -0.33 to 0.84; P = 0.40; I² = 71% - Head circumference: MD -0.15, 95% CI -0.53 to 0.23; P = 0.45; I² = 0%). No significant effect of LCPUFA on weight, length or head circumference was observed on meta-analysis of two studies (n = 396 infants) at 18 months (Weight: MD -0.14, 95% CI -0.39 to 0.10; P = 0.26; I² = 66% - Length: MD -0.28, 95% CI -0.91 to 0.35; P = 0.38; I² = 90% - Head circumference: MD -0.18, 95% CI -0.53 to 0.18; P = 0.32; I² = 0%). A GRADE analysis for this outcome indicated that the overall quality of evidence was low.

Authors' conclusions: Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. On pooling of results, no clear long-term benefits or harms were demonstrated for preterm infants receiving LCPUFA-supplemented formula.

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Conflict of interest statement

None.

Figures

1
1
Study 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: 1 Supplement vs control, outcome: 1.6 Visual acuity (log cycles/degree) at 12 months post‐term.
4
4
Forest plot of comparison: 1 Supplement vs control, outcome: 1.13 Bayley MDI at 12 months post‐term.
5
5
Forest plot of comparison: 1 Supplement vs control, outcome: 1.14 Bayley PDI at 12 months post‐term.
6
6
Forest plot of comparison: 1 Supplement vs control, outcome: 1.28 Weight at 12 months post‐term (kg).
7
7
Forest plot of comparison: 1 Supplement vs control, outcome: 1.29 Length at 12 months post‐term (cm).
8
8
Forest plot of comparison: 1 Supplement vs control, outcome: 1.30 Head circumference at 12 months post‐term (cm).
1.1
1.1. Analysis
Comparison 1 Supplement vs control, Outcome 1 Visual acuity (log cycles/degree) at term.
1.2
1.2. Analysis
Comparison 1 Supplement vs control, Outcome 2 Visual acuity (log cycles/degree) at 2 months post‐term.
1.3
1.3. Analysis
Comparison 1 Supplement vs control, Outcome 3 Visual acuity (log cycles/ degree) at 4 months post‐term.
1.4
1.4. Analysis
Comparison 1 Supplement vs control, Outcome 4 Visual acuity (log cycles /degree) at 6 months post‐term.
1.5
1.5. Analysis
Comparison 1 Supplement vs control, Outcome 5 Visual acuity (log cycles/degree) at 9 months post‐term.
1.6
1.6. Analysis
Comparison 1 Supplement vs control, Outcome 6 Visual acuity (log cycles/degree) at 12 months post‐term.
1.7
1.7. Analysis
Comparison 1 Supplement vs control, Outcome 7 Rod ERG at 36 wk PCA.
1.8
1.8. Analysis
Comparison 1 Supplement vs control, Outcome 8 ERG at 3 months post‐term, amplitude (uV).
1.9
1.9. Analysis
Comparison 1 Supplement vs control, Outcome 9 Rod ERG at 4 months post‐term.
1.10
1.10. Analysis
Comparison 1 Supplement vs control, Outcome 10 VEP at 3 months post‐term.
1.11
1.11. Analysis
Comparison 1 Supplement vs control, Outcome 11 Fagan infant test at 12 months post‐term.
1.12
1.12. Analysis
Comparison 1 Supplement vs control, Outcome 12 Fagan infant test at 9 months post‐term (% total time).
1.13
1.13. Analysis
Comparison 1 Supplement vs control, Outcome 13 Bayley MDI at 12 months post‐term.
1.14
1.14. Analysis
Comparison 1 Supplement vs control, Outcome 14 Bayley PDI at 12 months post‐term.
1.15
1.15. Analysis
Comparison 1 Supplement vs control, Outcome 15 Weight at 6 wk post‐term (kg).
1.16
1.16. Analysis
Comparison 1 Supplement vs control, Outcome 16 Length at 6 wk post‐term (cm).
1.17
1.17. Analysis
Comparison 1 Supplement vs control, Outcome 17 Head circumference at 6 wk post‐term (cm).
1.18
1.18. Analysis
Comparison 1 Supplement vs control, Outcome 18 Weight at term (kg).
1.19
1.19. Analysis
Comparison 1 Supplement vs control, Outcome 19 Length at term (cm).
1.20
1.20. Analysis
Comparison 1 Supplement vs control, Outcome 20 Head circ at term (cm).
1.21
1.21. Analysis
Comparison 1 Supplement vs control, Outcome 21 Weight at 2 months post‐term (kg).
1.22
1.22. Analysis
Comparison 1 Supplement vs control, Outcome 22 Length at 2 months post‐term (cm).
1.23
1.23. Analysis
Comparison 1 Supplement vs control, Outcome 23 Head circumference at 2 months post‐term (cm).
1.24
1.24. Analysis
Comparison 1 Supplement vs control, Outcome 24 Growth rate until 3 months post‐term.
1.25
1.25. Analysis
Comparison 1 Supplement vs control, Outcome 25 Weight at 4 months post‐term (kg).
1.26
1.26. Analysis
Comparison 1 Supplement vs control, Outcome 26 Length at 4 months post‐term (cm).
1.27
1.27. Analysis
Comparison 1 Supplement vs control, Outcome 27 Head circumference at 4 months post‐term (cm).
1.28
1.28. Analysis
Comparison 1 Supplement vs control, Outcome 28 Weight at 12 months post‐term (kg).
1.29
1.29. Analysis
Comparison 1 Supplement vs control, Outcome 29 Length at 12 months post‐term (cm).
1.30
1.30. Analysis
Comparison 1 Supplement vs control, Outcome 30 Head circumference at 12 months post‐term (cm).
1.31
1.31. Analysis
Comparison 1 Supplement vs control, Outcome 31 Normalised weight at 12 months post‐term.
1.32
1.32. Analysis
Comparison 1 Supplement vs control, Outcome 32 Normalised length at 12 months post‐term.
1.33
1.33. Analysis
Comparison 1 Supplement vs control, Outcome 33 Normalised head circumference at 12 months post‐term.
1.34
1.34. Analysis
Comparison 1 Supplement vs control, Outcome 34 Lipid peroxidation (TBARS ‐azide/+azide x 100%), 4 months post‐term.
1.35
1.35. Analysis
Comparison 1 Supplement vs control, Outcome 35 RBC fragility (hemolysis with 8% to 10% H2O2) , 4 months post‐term.
1.36
1.36. Analysis
Comparison 1 Supplement vs control, Outcome 36 Infant bleeding time 4 months post‐term (ped device, min).
1.37
1.37. Analysis
Comparison 1 Supplement vs control, Outcome 37 Bayley MDI at 18 months post‐term.
1.38
1.38. Analysis
Comparison 1 Supplement vs control, Outcome 38 Bayley PDI at 18 months post‐term.
1.39
1.39. Analysis
Comparison 1 Supplement vs control, Outcome 39 KPS Developmental Screening Inventory at 9 months post‐term (overall quotient).
1.40
1.40. Analysis
Comparison 1 Supplement vs control, Outcome 40 Weight at 9 months post‐term.
1.41
1.41. Analysis
Comparison 1 Supplement vs control, Outcome 41 Length at 9 months post‐term.
1.42
1.42. Analysis
Comparison 1 Supplement vs control, Outcome 42 Head circumference at 9 months post‐term.
1.43
1.43. Analysis
Comparison 1 Supplement vs control, Outcome 43 Normailsed weight at 9 months post‐term.
1.44
1.44. Analysis
Comparison 1 Supplement vs control, Outcome 44 Normalised length at 9 months post‐term.
1.45
1.45. Analysis
Comparison 1 Supplement vs control, Outcome 45 Normalised head circumference at 9 months post‐term.
1.46
1.46. Analysis
Comparison 1 Supplement vs control, Outcome 46 Weight at 18 months post‐term.
1.47
1.47. Analysis
Comparison 1 Supplement vs control, Outcome 47 Length at 18 months post‐term.
1.48
1.48. Analysis
Comparison 1 Supplement vs control, Outcome 48 Head circumference at 18 months post‐term.
1.49
1.49. Analysis
Comparison 1 Supplement vs control, Outcome 49 Normalised weight at 18 months post‐term.
1.50
1.50. Analysis
Comparison 1 Supplement vs control, Outcome 50 Normalised length at 18 months post‐term.
1.51
1.51. Analysis
Comparison 1 Supplement vs control, Outcome 51 Normalised head circumference at 18 months post‐term.
1.52
1.52. Analysis
Comparison 1 Supplement vs control, Outcome 52 Fagan Infant test at 6m post‐term, novelty time (%total time).
1.53
1.53. Analysis
Comparison 1 Supplement vs control, Outcome 53 MacArthur Communicative Inventories at 14 months post‐term.
1.54
1.54. Analysis
Comparison 1 Supplement vs control, Outcome 54 Bayley MDI at 24 months post‐term.
1.55
1.55. Analysis
Comparison 1 Supplement vs control, Outcome 55 Bayley PDI at 24 months post‐term.
1.56
1.56. Analysis
Comparison 1 Supplement vs control, Outcome 56 Weight at 10 years.
1.57
1.57. Analysis
Comparison 1 Supplement vs control, Outcome 57 Height at 10 years.
1.58
1.58. Analysis
Comparison 1 Supplement vs control, Outcome 58 Head circumference at 10 years.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Almaas 2015 {published data only}
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References to other published versions of this review

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