Breastfeeding or breast milk for procedural pain in neonates

Prakeshkumar S Shah; Cecilia Herbozo; Lucia Liz Aliwalas; Vibhuti S Shah

doi:10.1002/14651858.CD004950.pub3

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

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

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Figure 4

Forest plot of comparison: 1 Breastfeeding vs control, outcome: 1.9 Neonatal Facial Coding Score (NFCS).

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Figure 5

Forest plot of comparison: 2 Supplemental breast milk vs control, outcome: 2.8 Neonatal Facial Coding Score (NFCS) at 2 minutes.

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Figure 6

Forest plot of comparison: 2 Supplemental breast milk vs control, outcome: 2.9 Douleur Aigue du Nouveau‐né (DAN) at 2 minutes.

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Analysis 1.1

Comparison 1 Breastfeeding vs control, Outcome 1 Heart rate change (beats per minute).

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Analysis 1.2

Comparison 1 Breastfeeding vs control, Outcome 2 Oxygen saturation change.

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Analysis 1.3

Comparison 1 Breastfeeding vs control, Outcome 3 Blood pressure changes (mm of Hg).

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Analysis 1.4

Comparison 1 Breastfeeding vs control, Outcome 4 Percentage of time crying.

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Analysis 1.5

Comparison 1 Breastfeeding vs control, Outcome 5 Duration of crying (seconds).

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Analysis 1.6

Comparison 1 Breastfeeding vs control, Outcome 6 Duration of first cry (seconds).

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Analysis 1.7

Comparison 1 Breastfeeding vs control, Outcome 7 Neonatal Infant Pain Scale (NIPS).

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Analysis 1.8

Comparison 1 Breastfeeding vs control, Outcome 8 Premature Infant Pain Profile Score.

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Analysis 1.9

Comparison 1 Breastfeeding vs control, Outcome 9 Neonatal Facial Coding System (NFCS).

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Analysis 1.10

Comparison 1 Breastfeeding vs control, Outcome 10 Douleur Aigue Nouveau‐né (DAN) Scale.

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Analysis 1.11

Comparison 1 Breastfeeding vs control, Outcome 11 Composite score.

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Analysis 2.1

Comparison 2 Supplemental breast milk vs control, Outcome 1 Heart rate change (beats per minute).

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Analysis 2.2

Comparison 2 Supplemental breast milk vs control, Outcome 2 Oxygen saturation change.

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Analysis 2.3

Comparison 2 Supplemental breast milk vs control, Outcome 3 Percentage of time crying.

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Analysis 2.4

Comparison 2 Supplemental breast milk vs control, Outcome 4 Duration of crying (seconds).

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Analysis 2.5

Comparison 2 Supplemental breast milk vs control, Outcome 5 Duration of first cry (seconds).

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Analysis 2.6

Comparison 2 Supplemental breast milk vs control, Outcome 6 Neonatal Infant pain scale (NIPS).

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Analysis 2.7

Comparison 2 Supplemental breast milk vs control, Outcome 7 Neonatal Facial Coding Score at 3 minutes.

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Analysis 2.8

Comparison 2 Supplemental breast milk vs control, Outcome 8 Neonatal Facial Coding Score (NFCS) at 2 minutes.

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Analysis 2.9

Comparison 2 Supplemental breast milk vs control, Outcome 9 Douleur Aigue du Nouveau‐né (DAN) at 2 minutes.

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Analysis 2.10

Comparison 2 Supplemental breast milk vs control, Outcome 10 Body pain score.

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Breastfeeding compared with control for procedural pain relief
Patient or population: Healthy full‐term newborns Settings: Neonatal ward Intervention: Breastfeeding or supplemental breast milk Comparison: Control
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Breastfeeding or supplemental breast milk
Percentage of time crying (Breastfeeding versus control)	The mean percentage of time crying ranged across control groups from 43% to 65.6%	The mean percentage of time crying in the intervention groups was lower and ranged from 4% to 33%		227	⊕⊕⊕⊝ moderate	Three studies evaluated this outcome, and overall there was a statistically significant reduction in percentage of time crying in the breastfeeding group
Duration of crying (seconds) (Breastfeeding versus control)	The mean duration of crying ranged across control groups from 5 to 184 seconds	The mean duration of crying in the intervention groups was lower and ranged from 8.8 to 75.8 seconds		539	⊕⊕⊕⊝ moderate	There seems to be a tendency towards a reduction in duration of crying in the breastfeeding group, except when it was compared with formula feeding
Neonatal Infant Pain Scale (NIPS) (Breastfeeding versus control)	The mean NIPS ranged across control groups from 0.3 to 5.6	The mean NIPS in the intervention groups was lower, with a mean of 0.9		102	⊕⊕⊕⊝ moderate	Only one study evaluated this outcome and there was no statistically significant difference between breastfeeding and sucrose, but there was a decrease in NIPS when compared to no intervention
Neonatal Facial Coding Score (NFCS) (Breastfeeding versus control)	The mean NFCS ranged across control groups from 0.94 to 7.1	The mean NFCS in the intervention groups was lower, ranging from 0.62 to 2.9		240	⊕⊕⊕⊝ moderate	Two studies evaluated NFCS.,Breastfeeding reduced NFCS, except when compared with formula feeding (where there was no statistically significant difference)
Percentage of time crying (Supplemental breast milk versus control)	The mean percentage of time crying ranged across control groups from 76% to 90%	The mean percentage of time crying in the intervention groups was higher, with a mean of 91%		80	⊕⊕⊕ moderate	Only one study evaluated this outcome, and there was no statistically significant difference between supplemental breast milk and control
Duration of crying (seconds) (Supplemental breast milk versus control)	The mean duration of crying ranged across control groups from 9.13 to 157.05 seconds	The mean duration of crying in the intervention groups was similar to control group, ranging from 22.04 to 151.34 seconds		730	⊕⊕⊕⊝ moderate	Seven studies evaluated this outcome, and there was no statistically significant difference between supplemental breast milk and control
Neonatal Infant Pain Scale (NIPS) (Supplemental breast milk versus control)	The mean NIPS ranged across control groups from 2.6 to 5.1	The mean NIPS in the intervention groups was similar with a mean score of 4.8		120	⊕⊕⊝⊝ moderate	Only one study evaluated this outcome. It did not show any statistically significant difference between supplemental breast milk and control groups, but it was a low quality study
Neonatal Facial Coding Score (NFCS) at 3 minutes (Supplemental breast milk versus control)	The mean NFCS at 3 minutes ranged across control groups from 2.6 to 3.54	The mean NFCS at 3 minutes in the intervention groups was similar, ranging from 0.6 to 3.08		223	⊕⊕⊕⊝ moderate	No statistically significant difference was shown between supplemental breast milk and control
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval
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.

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Comparison 1. Breastfeeding vs control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Heart rate change (beats per minute) Show forest plot	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 Breastfeeding vs positioning	1	30	Mean Difference (IV, Fixed, 95% CI)	‐23.0 [‐34.55, ‐11.45]
1.2 Breastfeeding vs pacifier use (neonate held by mother)	2	126	Mean Difference (IV, Fixed, 95% CI)	‐12.02 [‐18.90, ‐5.13]
1.3 Breastfeeding vs pacifier use (neonate held by research assistant)	1	54	Mean Difference (IV, Fixed, 95% CI)	‐7.10 [‐15.50, 1.30]
1.4 Breastfeeding vs oral sucrose	1	101	Mean Difference (IV, Fixed, 95% CI)	‐9.0 [‐14.41, ‐3.59]
1.5 Breastfeeding vs held by mother	1	60	Mean Difference (IV, Fixed, 95% CI)	‐17.0 [‐25.51, ‐8.49]
1.6 Breastfeeding vs formula feeding	1	61	Mean Difference (IV, Fixed, 95% CI)	2.10 [‐4.78, 8.98]
1.7 Breastfeeding vs 30% glucose solution	1	62	Mean Difference (IV, Fixed, 95% CI)	‐4.30 [‐12.33, 3.73]
1.8 Breastfeeding vs no intervention	1	60	Mean Difference (IV, Fixed, 95% CI)	‐13.0 [‐21.74, ‐4.26]
2 Oxygen saturation change Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 Breastfeeding vs pacifier use (neonate held by mother)	1	64	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐2.79, 3.39]
2.2 Breastfeeding vs pacifier use (neonate held by research assistant)	1	53	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐1.48, 2.68]
2.3 Breastfeeding vs oral sucrose (25%)	1	101	Mean Difference (IV, Fixed, 95% CI)	2.0 [0.38, 3.62]
3 Blood pressure changes (mm of Hg) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

3.1 Breastfeeding vs pacifier use (neonate held by mother)	1	62	Mean Difference (IV, Fixed, 95% CI)	‐3.60 [‐9.08, 1.88]
3.2 Breastfeeding vs pacifier use (neonate held by research assistant)	1	48	Mean Difference (IV, Fixed, 95% CI)	1.60 [‐4.86, 8.06]
4 Percentage of time crying Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 Breastfeeding vs positioning	1	30	Mean Difference (IV, Fixed, 95% CI)	‐39.0 [‐55.03, ‐22.97]
4.2 Breastfeeding vs pacifier use (neonate held by mother)	1	71	Mean Difference (IV, Fixed, 95% CI)	‐11.80 [‐27.95, 4.35]
4.3 Breastfeeding vs pacifier use (neonate held by research assistant)	1	57	Mean Difference (IV, Fixed, 95% CI)	‐32.60 [‐49.83, ‐15.37]
4.4 Breastfeeding vs oral sucrose (25%)	1	101	Mean Difference (IV, Fixed, 95% CI)	‐41.5 [‐48.01, ‐34.99]
5 Duration of crying (seconds) Show forest plot	5		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 Breastfeeding vs no treatment	3	179	Mean Difference (IV, Fixed, 95% CI)	‐41.34 [‐49.53, ‐33.15]
5.2 Breastfeeding vs sucrose/glucose	3	183	Mean Difference (IV, Fixed, 95% CI)	‐5.83 [‐11.50, ‐0.15]
5.3 Breastfeeding vs positioning	1	30	Mean Difference (IV, Fixed, 95% CI)	‐63.3 [‐74.54, ‐52.06]
5.4 Breastfeeding and skin‐to‐skin vs skin‐to‐skin	1	71	Mean Difference (IV, Fixed, 95% CI)	‐17.0 [‐41.63, 7.63]
5.5 Breastfeeding and skin‐to‐skin vs lying on a table	1	71	Mean Difference (IV, Fixed, 95% CI)	‐136.0 [‐180.45, ‐91.55]
5.6 Breastfeeding vs formula feeding	1	61	Mean Difference (IV, Fixed, 95% CI)	8.3 [3.93, 12.67]
5.7 Breastfeeding vs holding by mother	1	60	Mean Difference (IV, Fixed, 95% CI)	‐13.80 [‐21.93, ‐5.67]
5.8 Breastfeeding vs non‐nutritive sucking on pacifier	1	61	Mean Difference (IV, Fixed, 95% CI)	‐19.2 [‐29.05, ‐9.35]
6 Duration of first cry (seconds) Show forest plot	1	101	Mean Difference (IV, Fixed, 95% CI)	‐18.0 [‐25.80, ‐10.20]

7 Neonatal Infant Pain Scale (NIPS) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Breastfeeding vs 25% sucrose	1	68	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.11, 1.31]
7.2 Breastfeeding vs no intervention	1	68	Mean Difference (IV, Fixed, 95% CI)	‐4.70 [‐5.68, ‐3.72]
8 Premature Infant Pain Profile Score Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Breastfeeding vs placebo	1	89	Mean Difference (IV, Fixed, 95% CI)	‐5.95 [‐7.42, ‐4.48]
8.2 Breastfeeding vs no treatment	1	29	Mean Difference (IV, Fixed, 95% CI)	‐0.49 [‐2.39, 1.41]
8.3 Breastfeeding vs glucose	2	127	Mean Difference (IV, Fixed, 95% CI)	1.30 [0.05, 2.56]
8.4 Breastfeeding vs positioning	1	89	Mean Difference (IV, Fixed, 95% CI)	‐7.49 [‐8.95, ‐6.03]
8.5 Breastfeeding vs sucrose	1	101	Mean Difference (IV, Fixed, 95% CI)	‐5.5 [‐6.48, ‐4.52]
9 Neonatal Facial Coding System (NFCS) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 Breastfeeding vs formula feeding	1	61	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.63, 1.83]
9.2 Breastfeeding vs 30% glucose	1	62	Mean Difference (IV, Fixed, 95% CI)	‐3.9 [‐4.80, ‐1.00]
9.3 Breastfeeding vs holding by mother	2	120	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐0.44, ‐0.23]
9.4 Breastfeeding vs non‐nutritive sucking with pacifier	1	61	Mean Difference (IV, Fixed, 95% CI)	‐2.00 [‐3.15, ‐0.85]
9.5 Breastfeeding vs no intervention	1	60	Mean Difference (IV, Fixed, 95% CI)	‐4.20 [‐5.14, ‐3.26]
10 Douleur Aigue Nouveau‐né (DAN) Scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

10.1 Breastfeeding vs placebo	1	89	Mean Difference (IV, Fixed, 95% CI)	‐6.24 [‐7.38, ‐5.10]
10.2 Breastfeeding vs sucrose/glucose	1	89	Mean Difference (IV, Fixed, 95% CI)	‐0.75 [‐1.97, 0.47]
10.3 Breastfeeding vs positioning	1	89	Mean Difference (IV, Fixed, 95% CI)	‐6.77 [‐7.78, ‐5.76]
11 Composite score Show forest plot	1	100	Mean Difference (IV, Fixed, 95% CI)	‐2.90 [‐3.51, ‐2.29]

Comparison 1. Breastfeeding vs control

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Comparison 2. Supplemental breast milk vs control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Heart rate change (beats per minute) Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 Supplemental breast milk vs placebo	5	300	Mean Difference (IV, Fixed, 95% CI)	‐4.49 [‐7.08, ‐1.89]
1.2 Supplemental breast milk vs no treatment	1	60	Mean Difference (IV, Fixed, 95% CI)	‐5.10 [‐12.37, 2.17]
1.3 Supplemental breast milk vs 25% sucrose	1	68	Mean Difference (IV, Fixed, 95% CI)	13.80 [4.23, 23.37]
1.4 Supplemental breast milk vs 10% glucose	2	110	Mean Difference (IV, Fixed, 95% CI)	0.62 [‐1.79, 3.03]
1.5 Supplemental breast milk vs 25% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	9.00 [7.00, 11.00]
1.6 Supplemental breast milk vs 30% glucose	1	60	Mean Difference (IV, Fixed, 95% CI)	6.80 [0.70, 12.90]
1.7 Supplemental breast milk vs 50% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	10.10 [8.08, 12.12]
1.8 Supplemental breast milk vs artificial sweetener	1	40	Mean Difference (IV, Fixed, 95% CI)	8.0 [‐0.15, 16.15]
1.9 Supplemental breast milk vs glycine	1	40	Mean Difference (IV, Fixed, 95% CI)	4.0 [‐2.82, 10.82]
2 Oxygen saturation change Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 Supplemental breast milk vs placebo	2	131	Mean Difference (IV, Fixed, 95% CI)	‐1.11 [‐1.99, ‐0.24]
2.2 Supplemental breast milk vs 10% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐0.88, 1.28]
2.3 Supplemental breast milk vs 25% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	2.0 [1.03, 2.97]
2.4 Supplemental breast milk vs 50% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	2.10 [1.22, 2.98]
3 Percentage of time crying Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

3.1 Supplemental breast milk vs placebo	1	40	Mean Difference (IV, Fixed, 95% CI)	9.0 [‐1.99, 19.99]
3.2 Supplemental breast milk vs artificial sweetener	1	40	Mean Difference (IV, Fixed, 95% CI)	15.0 [2.38, 27.62]
3.3 Supplemental breast milk vs glycine	1	40	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐4.61, 6.61]
4 Duration of crying (seconds) Show forest plot	8		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 Supplemental breast milk vs placebo	7	357	Mean Difference (IV, Fixed, 95% CI)	‐8.67 [‐12.32, ‐5.02]
4.2 Supplemental breast milk vs 2 doses of placebo (water)	1	44	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐5.39, 5.39]
4.3 Supplemental breast milk vs 12.5% sucrose (single dose)	1	43	Mean Difference (IV, Fixed, 95% CI)	35.0 [29.04, 40.96]
4.4 Supplemental breast milk vs 12.5% sucrose (2 doses)	1	41	Mean Difference (IV, Fixed, 95% CI)	22.0 [13.09, 30.91]
4.5 Supplemental breast milk vs 20% sucrose	2	95	Mean Difference (IV, Fixed, 95% CI)	10.50 [4.10, 16.91]
4.6 Supplemental breast milk vs 25% sucrose	1	68	Mean Difference (IV, Fixed, 95% CI)	33.17 [12.08, 54.26]
4.7 Supplemental breast milk vs 10% glucose	2	110	Mean Difference (IV, Fixed, 95% CI)	3.58 [‐1.52, 8.68]
4.8 Supplemental breast milk vs 25% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	29.76 [24.14, 35.38]
4.9 Supplemental breast milk vs 30% glucose	1	60	Mean Difference (IV, Fixed, 95% CI)	12.91 [‐3.26, 29.08]
4.10 Supplemental breast milk vs 50% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	27.2 [20.89, 33.51]
4.11 Supplemental breast milk vs artificial sweetener	1	40	Mean Difference (IV, Fixed, 95% CI)	41.0 [‐6.61, 88.61]
4.12 Supplemental breast milk vs glycine	1	40	Mean Difference (IV, Fixed, 95% CI)	51.8 [6.33, 97.27]
4.13 Supplemental breast milk vs non‐nutritive sucking (pacifier)	2	98	Mean Difference (IV, Fixed, 95% CI)	44.23 [38.47, 49.98]
4.14 Supplemental breast milk vs massage	1	35	Mean Difference (IV, Fixed, 95% CI)	‐9.0 [‐16.97, ‐1.03]
4.15 Supplemental breast milk vs rocking	1	35	Mean Difference (IV, Fixed, 95% CI)	31.0 [24.47, 37.53]
4.16 Supplemental breast milk vs no intervention	1	60	Mean Difference (IV, Fixed, 95% CI)	36.7 [0.60, 72.80]
4.17 Supplemental breast milk vs two doses of supplemental breast milk	1	41	Mean Difference (IV, Fixed, 95% CI)	‐11.0 [‐21.22, ‐0.78]
5 Duration of first cry (seconds) Show forest plot	2	376	Mean Difference (IV, Fixed, 95% CI)	4.58 [3.32, 5.85]

5.1 Supplemental breast milk vs 20% sucrose	1	35	Mean Difference (IV, Fixed, 95% CI)	6.0 [2.50, 9.50]
5.2 Supplemental breast milk vs placebo (water)	2	83	Mean Difference (IV, Fixed, 95% CI)	‐3.77 [‐6.73, ‐0.82]
5.3 Supplemental breast milk vs non‐nutritive sucking (pacifier)	1	38	Mean Difference (IV, Fixed, 95% CI)	4.0 [0.18, 7.82]
5.4 Supplemental breast milk vs massage	1	35	Mean Difference (IV, Fixed, 95% CI)	‐6.0 [‐12.34, 0.34]
5.5 Supplemental breast milk vs rocking	1	35	Mean Difference (IV, Fixed, 95% CI)	3.0 [‐1.52, 7.52]
5.6 Supplemental breast milk vs 10% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	1.92 [‐1.38, 5.22]
5.7 Supplemental breast milk vs 25% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	12.78 [9.36, 16.20]
5.8 Supplemental breast milk vs 50% glucose	1	50	Mean Difference (IV, Fixed, 95% CI)	11.56 [8.54, 14.58]
6 Neonatal Infant pain scale (NIPS) Show forest plot	1	180	Mean Difference (IV, Fixed, 95% CI)	1.07 [0.33, 1.81]

6.1 Supplemental breast milk vs 20% sucrose	1	60	Mean Difference (IV, Fixed, 95% CI)	2.20 [0.97, 3.43]
6.2 Supplemental breast milk vs non‐nutritive sucking (pacifier)	1	60	Mean Difference (IV, Fixed, 95% CI)	1.20 [‐0.14, 2.54]
6.3 Supplemental breast milk vs no intervention	1	60	Mean Difference (IV, Fixed, 95% CI)	‐0.30 [‐1.60, 1.00]
7 Neonatal Facial Coding Score at 3 minutes Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Supplemental breast milk vs placebo	3	183	Mean Difference (IV, Fixed, 95% CI)	‐0.57 [‐0.97, ‐0.16]
7.2 Supplemental breast milk vs artificial sweetener	1	40	Mean Difference (IV, Fixed, 95% CI)	‐0.22 [‐0.65, 0.21]
7.3 Supplemental breast milk vs glycine	1	40	Mean Difference (IV, Fixed, 95% CI)	‐0.47 [‐0.90, ‐0.04]
8 Neonatal Facial Coding Score (NFCS) at 2 minutes Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Supplemental breast milk vs placebo (water)	1	45	Mean Difference (IV, Fixed, 95% CI)	‐0.84 [‐1.09, ‐0.59]
8.2 Supplemental breast milk vs placebo (2 doses of water)	1	44	Mean Difference (IV, Fixed, 95% CI)	‐0.59 [‐0.83, ‐0.35]
8.3 Supplemental breast milk vs 12.5% sucrose (single dose)	1	43	Mean Difference (IV, Fixed, 95% CI)	0.92 [0.64, 1.20]
8.4 Supplemental breast milk vs 12.5% sucrose (2 doses)	1	41	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐0.11, 0.43]
8.5 Supplemental breast milk vs two doses of supplemental breast milk	1	41	Mean Difference (IV, Fixed, 95% CI)	‐1.14 [‐1.37, ‐0.91]
9 Douleur Aigue du Nouveau‐né (DAN) at 2 minutes Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 Supplemental breast milk vs 20% sucrose	1	35	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.30, 0.50]
9.2 Supplemental breast milk vs placebo (water)	1	33	Mean Difference (IV, Fixed, 95% CI)	‐1.10 [‐1.65, ‐0.55]
9.3 Supplemental breast milk vs non‐nutritive sucking (pacifier)	1	38	Mean Difference (IV, Fixed, 95% CI)	0.80 [0.40, 1.20]
9.4 Supplemental breast milk vs massage	1	35	Mean Difference (IV, Fixed, 95% CI)	‐0.5 [‐0.91, ‐0.09]
9.5 Supplemental breast milk vs rocking	1	35	Mean Difference (IV, Fixed, 95% CI)	1.1 [0.65, 1.55]
10 Body pain score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

10.1 Supplemental breast milk vs placebo	1	40	Mean Difference (IV, Fixed, 95% CI)	0.48 [‐0.38, 1.34]
10.2 Supplemental breast milk vs artificial sweetener	1	40	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐0.72, 1.04]
10.3 Supplemental breast milk vs glycine	1	40	Mean Difference (IV, Fixed, 95% CI)	0.43 [‐0.51, 1.37]

Comparison 2. Supplemental breast milk vs control

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