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Administración de suplementos de ácidos grasos poliinsaturados de cadena larga para los recién nacidos a término

Appendices

Appendix 1. Appendix 1: MEDLINE search strategy

Ovid MEDLINE(R) 1946 to present with daily update, Ovid MEDLINE(R) daily epub ahead of print, in‐process & other non‐indexed citations (28 December 2016)

1. Polyunsaturated fatty acid.mp. or Fatty Acids, Unsaturated/: 24403 citations

2. Fish Oils/ or Docosahexaenoic Acids/ or docosahexanoic acid.mp. or Fatty Acids, Omega‐3/: 24019 citations

3. n3 fatty acid.mp. : 35 citations

4. n6 fatty acid.mp: 10 citations

5. Arachidonic acid.mp. or arachidonic acid/: 44933 citations

6. 1 or 2 or 3 or 4 or 5: 82726 citations

7. Infant/ or Infant, Newborn/ or Infant Formula/: 1132619 citations

8. 6 and 7: 2304 Citations

9. limit 8 to (clinical trial or controlled clinical trial or pragmatic clinical trial or randomised controlled trial): 508 citations

Appendix 2. Appendix 2: Embase search strategy

Embase (Ovid)

1980 to 28 December 2016

1. Polyunsaturated fatty acid.mp. or Fatty Acids, Unsaturated/: 33673 citations

2. Fish Oils/ or Docosahexaenoic Acids/ or docosahexanoic acid.mp. or Fatty Acids, Omega‐3/: 41081 citations

3. n3 fatty acid.mp. : 41 citations

4. n6 fatty acid.mp: 8 citations

5. Arachidonic acid.mp. or arachidonic acid/: 55542 citations

6. 1 or 2 or 3 or 4 or 5: 111096 citations

7. Infant/ or Infant, Newborn/ or Infant Formula/: 945827 citations

8. 6 and 7: 3782 Citations

9. limit 7 to (clinical trial or controlled clinical trial or pragmatic clinical trial or randomised controlled trial): 581 citations

Appendix 3. Appendix 3: CINAHL search strategy

S1

docosahexanoic acid: 2583 citations

S2

omega‐3: 6657 citations

S3

Omega‐6: 997 citations

S4

arachidonic acid: 1711

S5

poly unsaturated fatty acid:16 citations

S6

polyunsaturated fatty acids: 2192 citations

S7

fish oil: 3059 citations

S8

n‐3 fatty acid: 784 citations

S9

n‐3 fatty acids: 784 citations

S10

n‐6 fatty acids:119 citations

S11

infant: 208105 citations

S12

newborn infant:1851 citations

S13

infant formula:3235 citations

S14

S11 OR S12 OR S13: 208105 citations

S15

S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10: 11103 citations

S16

S14 AND S15: 906 citations

Appendix 4. Appendix 4: Cochrane CENTRAL search strategy

#1. "long chain polyunsaturated fatty acid"(Word variations have been searched): 346 Citations

#2. Arachidonic Acid: 1378 Citations

#3. Docosahexanoic acid: 73 Citations

#4. Omega 3: Citations: 3734 Citations

#5. Omega 6: 2337 Citations

#6. Omega‐3: 3339 Citations

#7. Omega‐6: 475 Citations

#8. LCPUFA: 162 Citations

#9. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8: 5054 Citations

#10. Infant: 39347 Citations

#11. Neonate: 1322 Citations

#12. Newborn Infant: 17586 Citations

#13. Milk Formula: 1599 Citations

#14. Formula Milk: 1599 Citations

#15. #10 OR #11 or #12 or #13 or #14:39948 Citations

#16. #9 AND #15: 505 Citations

Appendix 5. Appendix 5: Risk of bias tool

Risk of bias of studies was assessed by two review authors (SR and BJ). We resolved disagreements by discussion among all four review authors and by consensus. We entered information into the Risk of bias table using the following criteria.

1. Was there adequate sequence generation (checking for possible selection bias): The method used to generate the allocation sequence in each included study was described as low risk (any truly random process, e.g. random number table, computer random number generator); high risk (any non‐random process, e.g. odd or even date of birth, hospital or clinic record number); unclear risk.

2. Was there adequate allocation concealment (checking for possible selection bias): The method used to conceal the allocation sequence in each included study was described as: low risk (e.g. telephone or central randomisation, consecutively numbered sealed opaque envelopes); high risk (open random allocation, unsealed or non‐opaque envelopes, alternation, date of birth); unclear risk.

3. Was there adequate blinding (checking for possible performance bias): The methods used to blind personnel from knowledge of which intervention participants received. Was knowledge of the allocated intervention adequately prevented during the study? At the time of outcome assessment? Categorised as low risk, high risk or unclear risk.

4. Were incomplete outcome data addressed (checking for possible attrition bias through withdrawals, dropouts, protocol deviations): If attrition and exclusion were reported, numbers included in the analysis at each stage (compared with total randomised participants), reasons for attrition or exclusion when reported and whether missing data were balanced across groups or were related to outcomes were reported. We assessed methods as low risk (< 20% missing data); high risk (≥ 20% missing data); unclear risk.

5. Was there selective reporting bias: The possibility of selective outcome reporting bias was investigated. We assessed methods as low risk (when it was clear that all of the study's prespecified outcomes were reported); high risk (when not all of the study's prespecified outcomes were reported; one or more reported primary outcomes were not prespecified; outcomes of interest were reported incompletely; study failed to include results of a key outcome that would have been expected to have been reported); unclear risk.

6. Were there any other sources of potential bias: Any important concerns about other potential sources of bias (e.g. whether a potential source of bias was related to the specific study design, whether the trial was stopped early owing to some data‐dependent process) were described. We assessed whether each study was free of other problems that could put it at risk of bias as low risk; high risk; unclear risk.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.10 Visual acuity/Teller cards at 12 m (cycles/degree).
Figures and Tables -
Figure 3

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.10 Visual acuity/Teller cards at 12 m (cycles/degree).

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.18 MDI (Bayley Scale score) at 18 m.
Figures and Tables -
Figure 4

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.18 MDI (Bayley Scale score) at 18 m.

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.19 PDI (Bayley Scale score) at 18 m.
Figures and Tables -
Figure 5

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.19 PDI (Bayley Scale score) at 18 m.

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.29 Weight at 12 m, z score.
Figures and Tables -
Figure 6

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.29 Weight at 12 m, z score.

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.31 Length at 12 m, z score.
Figures and Tables -
Figure 7

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.31 Length at 12 m, z score.

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.33 Head circumference at 12 m, z score.
Figures and Tables -
Figure 8

Forest plot of comparison: 1 LCPUFA supplemented vs control formula, outcome: 1.33 Head circumference at 12 m, z score.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 1 VEP acuity at 4 m (logMAR, steady state).
Figures and Tables -
Analysis 1.1

Comparison 1 LCPUFA supplemented vs control formula, Outcome 1 VEP acuity at 4 m (logMAR, steady state).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 2 Sweep VEP acuity at 4 m (logMAR).
Figures and Tables -
Analysis 1.2

Comparison 1 LCPUFA supplemented vs control formula, Outcome 2 Sweep VEP acuity at 4 m (logMAR).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 3 Sweep VEP acuity at 4 m (cycles/degree).
Figures and Tables -
Analysis 1.3

Comparison 1 LCPUFA supplemented vs control formula, Outcome 3 Sweep VEP acuity at 4 m (cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 4 Visual acuity/Teller cards at 4 m (cycles/degree).
Figures and Tables -
Analysis 1.4

Comparison 1 LCPUFA supplemented vs control formula, Outcome 4 Visual acuity/Teller cards at 4 m (cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 5 Sweep VEP acuity at 6 m (cycles/degree).
Figures and Tables -
Analysis 1.5

Comparison 1 LCPUFA supplemented vs control formula, Outcome 5 Sweep VEP acuity at 6 m (cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 6 Visual acuity/Teller cards at 6 m (cycles/degree).
Figures and Tables -
Analysis 1.6

Comparison 1 LCPUFA supplemented vs control formula, Outcome 6 Visual acuity/Teller cards at 6 m (cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 7 VEP acuity at 7‐8 m (logMAR, steady state).
Figures and Tables -
Analysis 1.7

Comparison 1 LCPUFA supplemented vs control formula, Outcome 7 VEP acuity at 7‐8 m (logMAR, steady state).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 8 Sweep VEP acuity at 12 months (logMAR).
Figures and Tables -
Analysis 1.8

Comparison 1 LCPUFA supplemented vs control formula, Outcome 8 Sweep VEP acuity at 12 months (logMAR).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 9 Sweep VEP acuity at 12 m (cycles/degree).
Figures and Tables -
Analysis 1.9

Comparison 1 LCPUFA supplemented vs control formula, Outcome 9 Sweep VEP acuity at 12 m (cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 10 Visual acuity/Teller cards at 12 m (cycles/degree).
Figures and Tables -
Analysis 1.10

Comparison 1 LCPUFA supplemented vs control formula, Outcome 10 Visual acuity/Teller cards at 12 m (cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 11 Visual acuity at 3 years (Teller acuity cards; cycles/degree).
Figures and Tables -
Analysis 1.11

Comparison 1 LCPUFA supplemented vs control formula, Outcome 11 Visual acuity at 3 years (Teller acuity cards; cycles/degree).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 12 MDI (Bayley) score at 3 m.
Figures and Tables -
Analysis 1.12

Comparison 1 LCPUFA supplemented vs control formula, Outcome 12 MDI (Bayley) score at 3 m.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 13 PDI (Bayley) score at 3 m.
Figures and Tables -
Analysis 1.13

Comparison 1 LCPUFA supplemented vs control formula, Outcome 13 PDI (Bayley) score at 3 m.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 14 MDI (Bayley) score at 6 m.
Figures and Tables -
Analysis 1.14

Comparison 1 LCPUFA supplemented vs control formula, Outcome 14 MDI (Bayley) score at 6 m.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 15 PDI (Bayley) score at 6 m.
Figures and Tables -
Analysis 1.15

Comparison 1 LCPUFA supplemented vs control formula, Outcome 15 PDI (Bayley) score at 6 m.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 16 MDI (Bayley score) at 1 year.
Figures and Tables -
Analysis 1.16

Comparison 1 LCPUFA supplemented vs control formula, Outcome 16 MDI (Bayley score) at 1 year.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 17 PDI (Bayley score) at 1 year.
Figures and Tables -
Analysis 1.17

Comparison 1 LCPUFA supplemented vs control formula, Outcome 17 PDI (Bayley score) at 1 year.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 18 MDI (Bayley score) at 18 m.
Figures and Tables -
Analysis 1.18

Comparison 1 LCPUFA supplemented vs control formula, Outcome 18 MDI (Bayley score) at 18 m.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 19 PDI (Bayley score) at 18 m.
Figures and Tables -
Analysis 1.19

Comparison 1 LCPUFA supplemented vs control formula, Outcome 19 PDI (Bayley score) at 18 m.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 20 MDI (Bayley score) at 2 years.
Figures and Tables -
Analysis 1.20

Comparison 1 LCPUFA supplemented vs control formula, Outcome 20 MDI (Bayley score) at 2 years.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 21 PDI (Bayley score) at 2 years.
Figures and Tables -
Analysis 1.21

Comparison 1 LCPUFA supplemented vs control formula, Outcome 21 PDI (Bayley score) at 2 years.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 22 Weight at 4 months.
Figures and Tables -
Analysis 1.22

Comparison 1 LCPUFA supplemented vs control formula, Outcome 22 Weight at 4 months.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 23 Length at 4 months.
Figures and Tables -
Analysis 1.23

Comparison 1 LCPUFA supplemented vs control formula, Outcome 23 Length at 4 months.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 24 Head circumference at 4 months.
Figures and Tables -
Analysis 1.24

Comparison 1 LCPUFA supplemented vs control formula, Outcome 24 Head circumference at 4 months.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 25 Weight at 6 m (kg).
Figures and Tables -
Analysis 1.25

Comparison 1 LCPUFA supplemented vs control formula, Outcome 25 Weight at 6 m (kg).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 26 Length at 6 m (cm).
Figures and Tables -
Analysis 1.26

Comparison 1 LCPUFA supplemented vs control formula, Outcome 26 Length at 6 m (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 27 Head circumference at 6 m (cm).
Figures and Tables -
Analysis 1.27

Comparison 1 LCPUFA supplemented vs control formula, Outcome 27 Head circumference at 6 m (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 28 Weight at 12 m (kg).
Figures and Tables -
Analysis 1.28

Comparison 1 LCPUFA supplemented vs control formula, Outcome 28 Weight at 12 m (kg).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 29 Weight at 12 m, z score.
Figures and Tables -
Analysis 1.29

Comparison 1 LCPUFA supplemented vs control formula, Outcome 29 Weight at 12 m, z score.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 30 Length at 12 m (cm).
Figures and Tables -
Analysis 1.30

Comparison 1 LCPUFA supplemented vs control formula, Outcome 30 Length at 12 m (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 31 Length at 12 m, z score.
Figures and Tables -
Analysis 1.31

Comparison 1 LCPUFA supplemented vs control formula, Outcome 31 Length at 12 m, z score.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 32 Head circumference at 12 m (cm).
Figures and Tables -
Analysis 1.32

Comparison 1 LCPUFA supplemented vs control formula, Outcome 32 Head circumference at 12 m (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 33 Head circumference at 12 m, z score.
Figures and Tables -
Analysis 1.33

Comparison 1 LCPUFA supplemented vs control formula, Outcome 33 Head circumference at 12 m, z score.

Comparison 1 LCPUFA supplemented vs control formula, Outcome 34 Weight at 18 m (kg).
Figures and Tables -
Analysis 1.34

Comparison 1 LCPUFA supplemented vs control formula, Outcome 34 Weight at 18 m (kg).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 35 Length at 18 m (cm).
Figures and Tables -
Analysis 1.35

Comparison 1 LCPUFA supplemented vs control formula, Outcome 35 Length at 18 m (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 36 Head circumference at 18 m (cm).
Figures and Tables -
Analysis 1.36

Comparison 1 LCPUFA supplemented vs control formula, Outcome 36 Head circumference at 18 m (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 37 Weight at 2 years (kg).
Figures and Tables -
Analysis 1.37

Comparison 1 LCPUFA supplemented vs control formula, Outcome 37 Weight at 2 years (kg).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 38 Height at 2 years (cm).
Figures and Tables -
Analysis 1.38

Comparison 1 LCPUFA supplemented vs control formula, Outcome 38 Height at 2 years (cm).

Comparison 1 LCPUFA supplemented vs control formula, Outcome 39 Head circumference at 2 years (cm).
Figures and Tables -
Analysis 1.39

Comparison 1 LCPUFA supplemented vs control formula, Outcome 39 Head circumference at 2 years (cm).

Summary of findings for the main comparison. LCPUFA supplemented formula compared with control formula for term infants

LCPUFA supplemented formula compared with control formula for term infants for clinical outcomes (visual function, neurodevelopment and physical growth)

Patient or population: term infants
Settings: hospital and community
Intervention: LCPUFA supplemented formula
Comparison: control formula

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control formula

LCPUFA supplemented formula

Visual acuity/Teller cards at 12 months (cycles/degree) ‐ DHA and AA vs normal term formula

Mean visual acuity (cycles/degree) ranged across control groups from 3.31 to 10

Mean visual acuity (cycles/degree) ranged across intervention groups from 3.28 to 9.77

MD ‐0.01 (95% CI ‐0.12 to 0.11)

256
(3 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition

Sweep VEP acuity at 12 months (LogMAR) ‐ DHA and AA vs normal term formula

Mean sweep VEP acuity (LogMAR) ranged across control groups from 0.31 to 0.339

Mean sweep VEP acuity (LogMAR) ranged across intervention groups from 0.14 to 0.2

MD ‐0.15 (95% CI ‐0.17 to ‐0.13)

244
(3 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition in 2 RCTs

MDI scores (Bayley) at 18 months ‐ DHA and AA vs normal term formula

Mean MDI ranged across control groups from 98.3 to 105.4

Mean MDI ranged across intervention groups from 94.5 to 105.6

MD 0.06 (95% CI ‐ 2.01 to 2.14)

661
(4 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition in 2 RCTs, high statistical heterogeneity
(I² = 75%)

PDI scores (Bayley) at 18 months ‐ DHA and AA vs normal term formula

Mean PDI ranged across control groups from 96.4 to 102

Mean PDI ranged across intervention groups from 95.9 to 105.8

MD 0.69 (95% CI ‐0.78 to 2.16)

661
(4 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition in 2 RCTs, high statistical heterogeneity
(I² = 61%)

Weight at 12 months (z scores) ‐ DHA and AA vs normal term formula

Mean z scores for weight ranged across control groups from ‐0.21 to 0.35

Mean z scores for weight ranged across intervention groups from ‐0.9 to 0.4

MD ‐0.23 (95% CI ‐0.40 to ‐0.06)

521
(5 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition in 3 RCTs, unclear allocation concealment in 2 RCTs, high statistical heterogeneity
(I² = 83%)

Length at 12 months (z scores) ‐ DHA and AA vs normal term formula

Mean z scores for length ranged across control groups from ‐0.11 to 0.34

Mean z scores for length ranged across control groups from ‐0.04 to 0.16

MD ‐0.04 (95% CI ‐0.19 to 0.11)

521
(5 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition in 3 RCTs, unclear allocation concealment in 2 RCTs

Head circumference at 12 months (z scores) ‐ DHA and AA vs normal term formula

Mean z scores for head circumference ranged across control groups from 0.18 to 0.94

Mean z scores for head circumference ranged across control groups from 0.01 to 0.93

MD ‐0.13 (95% CI ‐0.32 to 0.05)

464
(4 studies)

⊕⊕⊝⊝
low

Downgraded 2 levels
Reasons: small sample size, high rate of attrition in 3 RCTs

*The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: confidence interval; MD, mean difference

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: We are very uncertain about the estimate

Figures and Tables -
Summary of findings for the main comparison. LCPUFA supplemented formula compared with control formula for term infants
Comparison 1. LCPUFA supplemented vs control formula

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 VEP acuity at 4 m (logMAR, steady state) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 DHA and AA vs normal term formula

1

30

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.07, 0.09]

1.2 DHA vs normal term formula

2

60

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.10, 0.03]

2 Sweep VEP acuity at 4 m (logMAR) Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 DHA and AA vs normal term formula

3

266

Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.10, ‐0.05]

2.2 DHA vs normal term formula

1

41

Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.15, ‐0.01]

3 Sweep VEP acuity at 4 m (cycles/degree) Show forest plot

1

54

Mean Difference (IV, Fixed, 95% CI)

‐0.47 [‐1.16, 0.22]

3.1 DHA and AA vs normal term formula

1

54

Mean Difference (IV, Fixed, 95% CI)

‐0.47 [‐1.16, 0.22]

4 Visual acuity/Teller cards at 4 m (cycles/degree) Show forest plot

3

264

Mean Difference (IV, Fixed, 95% CI)

‐0.11 [‐0.24, 0.02]

4.1 DHA and AA vs normal term formula

3

264

Mean Difference (IV, Fixed, 95% CI)

‐0.11 [‐0.24, 0.02]

5 Sweep VEP acuity at 6 m (cycles/degree) Show forest plot

1

53

Mean Difference (IV, Fixed, 95% CI)

‐0.31 [‐1.04, 0.42]

5.1 DHA and AA vs normal term formula

1

53

Mean Difference (IV, Fixed, 95% CI)

‐0.31 [‐1.04, 0.42]

6 Visual acuity/Teller cards at 6 m (cycles/degree) Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 DHA and AA vs normal term formula

3

256

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.11, 0.15]

7 VEP acuity at 7‐8 m (logMAR, steady state) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

7.1 DHA and AA vs normal term formula

1

30

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.13, 0.13]

7.2 DHA vs normal term formula

2

52

Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐0.14, 0.10]

8 Sweep VEP acuity at 12 months (logMAR) Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

8.1 DHA and AA vs normal term formula

3

244

Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐0.17, ‐0.13]

8.2 DHA vs normal term formula

1

40

Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.21, ‐0.07]

9 Sweep VEP acuity at 12 m (cycles/degree) Show forest plot

1

53

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.71, 0.71]

9.1 DHA and AA vs normal term formula

1

53

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.71, 0.71]

10 Visual acuity/Teller cards at 12 m (cycles/degree) Show forest plot

3

256

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.12, 0.11]

10.1 DHA and AA vs normal term formula

3

256

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.12, 0.11]

11 Visual acuity at 3 years (Teller acuity cards; cycles/degree) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 DHA and AA vs normal term formula

1

68

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐2.41, ‐1.79]

11.2 DHA vs normal term formula

1

68

Mean Difference (IV, Fixed, 95% CI)

‐2.80 [‐3.11, ‐2.49]

12 MDI (Bayley) score at 3 m Show forest plot

1

58

Mean Difference (IV, Fixed, 95% CI)

2.48 [‐1.90, 6.86]

12.1 DHA and AA vs normal term formula

1

58

Mean Difference (IV, Fixed, 95% CI)

2.48 [‐1.90, 6.86]

13 PDI (Bayley) score at 3 m Show forest plot

1

58

Mean Difference (IV, Fixed, 95% CI)

3.66 [0.43, 6.89]

13.1 DHA and AA vs normal term formula

1

58

Mean Difference (IV, Fixed, 95% CI)

3.66 [0.43, 6.89]

14 MDI (Bayley) score at 6 m Show forest plot

2

207

Mean Difference (IV, Fixed, 95% CI)

‐0.59 [‐2.26, 1.07]

14.1 DHA and AA vs normal term formula

2

207

Mean Difference (IV, Fixed, 95% CI)

‐0.59 [‐2.26, 1.07]

15 PDI (Bayley) score at 6 m Show forest plot

2

206

Mean Difference (IV, Fixed, 95% CI)

0.23 [‐2.47, 2.94]

15.1 DHA and AA vs normal term formula

2

206

Mean Difference (IV, Fixed, 95% CI)

0.23 [‐2.47, 2.94]

16 MDI (Bayley score) at 1 year Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

16.1 DHA and AA vs normal term formula

3

298

Mean Difference (IV, Fixed, 95% CI)

‐0.95 [‐3.38, 1.49]

16.2 DHA vs normal term formula

3

160

Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐4.36, 3.83]

17 PDI (Bayley score) at 1 year Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

17.1 DHA and AA vs normal term formula

3

298

Mean Difference (IV, Fixed, 95% CI)

‐2.48 [‐5.83, 0.86]

17.2 DHA vs normal term formula

3

160

Mean Difference (IV, Fixed, 95% CI)

‐1.70 [‐6.62, 3.22]

18 MDI (Bayley score) at 18 m Show forest plot

4

661

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐2.01, 2.14]

18.1 DHA and AA vs normal term formula

4

661

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐2.01, 2.14]

19 PDI (Bayley score) at 18 m Show forest plot

4

661

Mean Difference (IV, Fixed, 95% CI)

0.69 [‐0.78, 2.16]

19.1 DHA and AA vs normal term formula

4

661

Mean Difference (IV, Fixed, 95% CI)

0.69 [‐0.78, 2.16]

20 MDI (Bayley score) at 2 years Show forest plot

1

79

Mean Difference (IV, Fixed, 95% CI)

1.85 [‐5.26, 8.96]

20.1 DHA and AA vs normal term formula

1

38

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐13.88, 9.88]

20.2 DHA vs normal term formula

1

41

Mean Difference (IV, Fixed, 95% CI)

4.0 [‐4.88, 12.88]

21 PDI (Bayley score) at 2 years Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

21.1 DHA and AA vs normal term formula

1

37

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐12.71, 10.71]

21.2 DHA vs normal term formula

1

37

Mean Difference (IV, Fixed, 95% CI)

7.00 [‐3.32, 17.32]

22 Weight at 4 months Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

22.1 DHA and AA vs normal term formula

1

46

Mean Difference (IV, Fixed, 95% CI)

0.15 [‐0.22, 0.52]

22.2 DHA vs normal term formula

2

71

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.33, 0.27]

23 Length at 4 months Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

23.1 DHA and AA vs normal term formula

1

46

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐1.45, 1.45]

23.2 DHA vs normal term formula

2

71

Mean Difference (IV, Fixed, 95% CI)

0.03 [1.00, 1.06]

24 Head circumference at 4 months Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

24.1 DHA and AA vs normal term formula

1

46

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐0.26, 1.26]

24.2 DHA vs normal term formula

2

71

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.53, 0.51]

25 Weight at 6 m (kg) Show forest plot

4

830

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.11, 0.13]

26 Length at 6 m (cm) Show forest plot

4

830

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.47, 0.21]

27 Head circumference at 6 m (cm) Show forest plot

4

830

Mean Difference (IV, Fixed, 95% CI)

‐0.06 [‐0.25, 0.13]

28 Weight at 12 m (kg) Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

28.1 DHA and AA vs normal term formula

5

689

Mean Difference (IV, Fixed, 95% CI)

‐0.11 [‐0.28, 0.05]

28.2 DHA vs normal term formula

2

75

Mean Difference (IV, Fixed, 95% CI)

‐0.43 [‐0.96, 0.09]

29 Weight at 12 m, z score Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

29.1 DHA and AA vs normal term formula

5

521

Mean Difference (IV, Fixed, 95% CI)

‐0.23 [‐0.40, ‐0.06]

29.2 DHA vs normal term formula

1

88

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.50, 0.48]

30 Length at 12 m (cm) Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

30.1 DHA and AA vs normal term formula

5

689

Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐0.57, 0.28]

30.2 DHA vs normal term formula

2

75

Mean Difference (IV, Fixed, 95% CI)

‐0.95 [‐2.05, 0.15]

31 Length at 12 m, z score Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

31.1 DHA and AA vs normal term formula

5

521

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.19, 0.11]

31.2 DHA vs normal term formula

1

88

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.35, 0.55]

32 Head circumference at 12 m (cm) Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

32.1 DHA and AA vs normal term formula

4

633

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.36, 0.11]

32.2 DHA vs normal term formula

2

75

Mean Difference (IV, Fixed, 95% CI)

‐0.22 [‐0.80, 0.37]

33 Head circumference at 12 m, z score Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

33.1 DHA and AA vs normal term formula

4

464

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.32, 0.05]

33.2 DHA vs normal term formula

1

88

Mean Difference (IV, Fixed, 95% CI)

0.07 [‐0.33, 0.47]

34 Weight at 18 m (kg) Show forest plot

2

563

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.25, 0.17]

34.1 DHA and AA vs normal term formula

2

563

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.25, 0.17]

35 Length at 18 m (cm) Show forest plot

2

565

Mean Difference (IV, Fixed, 95% CI)

‐0.19 [‐0.71, 0.34]

35.1 DHA and AA vs normal term formula

2

565

Mean Difference (IV, Fixed, 95% CI)

‐0.19 [‐0.71, 0.34]

36 Head circumference at 18 m (cm) Show forest plot

2

565

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.32, 0.19]

36.1 DHA and AA vs normal term formula

2

565

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.32, 0.19]

37 Weight at 2 years (kg) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

37.1 DHA and AA vs normal term formula

1

39

Mean Difference (IV, Fixed, 95% CI)

‐0.76 [‐1.68, 0.16]

37.2 DHA vs normal term formula

1

43

Mean Difference (IV, Fixed, 95% CI)

‐0.79 [‐1.65, 0.07]

38 Height at 2 years (cm) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

38.1 DHA and AA vs normal term formula

1

39

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐2.07, 2.07]

38.2 DHA vs normal term formula

1

43

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐2.09, 1.49]

39 Head circumference at 2 years (cm) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

39.1 DHA and AA vs normal term formula

1

39

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐0.47, 1.47]

39.2 DHA vs normal term formula

1

43

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.68, 0.88]

Figures and Tables -
Comparison 1. LCPUFA supplemented vs control formula