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Meta-Analysis
. 2017 Mar 10;3(3):CD000376.
doi: 10.1002/14651858.CD000376.pub4.

Long chain polyunsaturated fatty acid supplementation in infants born at term

Bonny Jasani  1 , Karen Simmer  2 , Sanjay K Patole  3 , Shripada C Rao  4
Affiliations
Meta-Analysis

Long chain polyunsaturated fatty acid supplementation in infants born at term

Bonny Jasani et al. Cochrane Database Syst Rev. .

Abstract

Background: The long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are considered essential for maturation of the developing brain, retina and other organs in newborn infants. Standard infant milk formulae are not supplemented with LCPUFA; they contain only alpha-linolenic acid and linoleic acid, from which formula-fed infants must synthesise their own DHA and AA, respectively. Over the past few years, some manufacturers have added LCPUFA to formula milk and have marketed these products as providing an advantage for the overall development of full-term infants.

Objectives: To assess whether supplementation of formula milk with LCPUFA is both safe and beneficial for full-term infants, while focusing on effects on visual function, neurodevelopment and physical growth.

Search methods: Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL; December 2016), MEDLINE (Ovid, 1966 to December 2016), Embase (Ovid, 1980 to December 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1980 to December 2016) and abstracts of the Pediatric Academic Societies (2000 to 2016). We applied no language restrictions.

Selection criteria: We reviewed all randomised controlled trials (RCTs) evaluating effects of LCPUFA supplemented versus non-supplemented formula milk on visual function, neurodevelopment and physical growth. We did not include trials reporting only biochemical outcomes.

Data collection and analysis: Two review authors extracted data independently. We assessed risk of bias of included studies using the guidelines of the Cochrane Neonatal Review Group. When appropriate, we conducted meta-analysis to determine a pooled estimate of effect.

Main results: We identified 31 RCTs and included 15 of these in the review (N = 1889).Nine studies assessed visual acuity, six of which used visual evoked potentials (VEP), two Teller cards and one both. Four studies reported beneficial effects, and the remaining five did not. Meta-analysis of three RCTs showed significant benefit for sweep VEP acuity at 12 months (log of the minimum angle of resolution (logMAR)) (mean difference (MD) -0.15, 95% confidence interval (CI) -0.17 to -0.13; I2 = 0; three trials; N = 244), but meta-analysis of three other RCTs showed no benefit for visual acuity measured with Teller cards at 12 months (cycles/degree) (MD -0.01, 95% CI -0.12 to 0.11; I2 = 0; three trials; N = 256). GRADE analysis for the outcome of visual acuity indicated that the overall quality of evidence was low.Eleven studies measured neurodevelopmental outcomes at or before two years. Nine studies used Bayley Scales of Infant Development, version II (BSID-II), and only two of these studies reported beneficial effects. Meta-analysis revealed no significant differences between LCPUFA and placebo groups in BSID Mental Developmental Index (MDI) scores at 18 months (MD 0.06, 95% CI -2.01 to 2.14; I2 = 75%; four trials; N = 661) and no significant differences in BSID Psychomotor Development Index (PDI) scores at 18 months (MD 0.69, 95% CI -0.78 to 2.16; I2 = 61%; four trials; N = 661). Results showed no significant differences between the two groups in BSID-II scores at one year and two years of age. One study reported better novelty preference measured by the Fagan Infant Test at nine months. Another study reported better problem solving at 10 months. One study used the Brunet and Lezine test to assess the developmental quotient and found no beneficial effects. Follow-up of some infants in different studies at three, six and nine years of age revealed no beneficial effects of supplementation. GRADE analysis of these outcomes indicated that the overall quality of evidence was low.Thirteen studies measured physical growth; none found beneficial or harmful effects of supplementation. Meta-analysis of five RCTs showed that the supplemented group had lower weight (z scores) at one year of age (MD -0.23, 95% CI -0.40 to -0.06; I2 = 83%; N = 521) and that the two groups showed no significant differences with respect to length and head circumference (z scores). Meta-analysis at 18 months and at two years revealed no significant differences between the two groups with respect to weight (kg), length (cm) and head circumference (cm). GRADE analysis of these outcomes indicated that the overall quality of evidence was low.

Authors' conclusions: Most of the included RCTs reported no beneficial effects or harms of LCPUFA supplementation on neurodevelopmental outcomes of formula-fed full-term infants and no consistent beneficial effects on visual acuity. Routine supplementation of full-term infant milk formula with LCPUFA cannot be recommended at this time.

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Conflict of interest statement

None.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.10 Visual acuity/Teller cards at 12 m (cycles/degree).
4
4
Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.18 MDI (Bayley Scale score) at 18 m.
5
5
Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.19 PDI (Bayley Scale score) at 18 m.
6
6
Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.29 Weight at 12 m, z score.
7
7
Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.31 Length at 12 m, z score.
8
8
Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.33 Head circumference at 12 m, z score.
1.1
1.1. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 1 VEP acuity at 4 m (logMAR, steady state).
1.2
1.2. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 2 Sweep VEP acuity at 4 m (logMAR).
1.3
1.3. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 3 Sweep VEP acuity at 4 m (cycles/degree).
1.4
1.4. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 4 Visual acuity/Teller cards at 4 m (cycles/degree).
1.5
1.5. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 5 Sweep VEP acuity at 6 m (cycles/degree).
1.6
1.6. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 6 Visual acuity/Teller cards at 6 m (cycles/degree).
1.7
1.7. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 7 VEP acuity at 7‐8 m (logMAR, steady state).
1.8
1.8. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 8 Sweep VEP acuity at 12 months (logMAR).
1.9
1.9. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 9 Sweep VEP acuity at 12 m (cycles/degree).
1.10
1.10. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 10 Visual acuity/Teller cards at 12 m (cycles/degree).
1.11
1.11. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 11 Visual acuity at 3 years (Teller acuity cards; cycles/degree).
1.12
1.12. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 12 MDI (Bayley) score at 3 m.
1.13
1.13. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 13 PDI (Bayley) score at 3 m.
1.14
1.14. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 14 MDI (Bayley) score at 6 m.
1.15
1.15. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 15 PDI (Bayley) score at 6 m.
1.16
1.16. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 16 MDI (Bayley score) at 1 year.
1.17
1.17. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 17 PDI (Bayley score) at 1 year.
1.18
1.18. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 18 MDI (Bayley score) at 18 m.
1.19
1.19. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 19 PDI (Bayley score) at 18 m.
1.20
1.20. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 20 MDI (Bayley score) at 2 years.
1.21
1.21. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 21 PDI (Bayley score) at 2 years.
1.22
1.22. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 22 Weight at 4 months.
1.23
1.23. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 23 Length at 4 months.
1.24
1.24. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 24 Head circumference at 4 months.
1.25
1.25. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 25 Weight at 6 m (kg).
1.26
1.26. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 26 Length at 6 m (cm).
1.27
1.27. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 27 Head circumference at 6 m (cm).
1.28
1.28. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 28 Weight at 12 m (kg).
1.29
1.29. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 29 Weight at 12 m, z score.
1.30
1.30. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 30 Length at 12 m (cm).
1.31
1.31. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 31 Length at 12 m, z score.
1.32
1.32. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 32 Head circumference at 12 m (cm).
1.33
1.33. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 33 Head circumference at 12 m, z score.
1.34
1.34. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 34 Weight at 18 m (kg).
1.35
1.35. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 35 Length at 18 m (cm).
1.36
1.36. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 36 Head circumference at 18 m (cm).
1.37
1.37. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 37 Weight at 2 years (kg).
1.38
1.38. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 38 Height at 2 years (cm).
1.39
1.39. Analysis
Comparison 1 LCPUFA supplemented vs control formula, Outcome 39 Head circumference at 2 years (cm).
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