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Meta-Analysis
. 2016 Jul 16;7(7):CD001069.
doi: 10.1002/14651858.CD001069.pub5.

Sucrose for analgesia in newborn infants undergoing painful procedures

Bonnie Stevens  1 , Janet Yamada, Arne Ohlsson, Sarah Haliburton, Allyson Shorkey
Affiliations
Meta-Analysis

Sucrose for analgesia in newborn infants undergoing painful procedures

Bonnie Stevens et al. Cochrane Database Syst Rev. .

Abstract

Background: Administration of oral sucrose with and without non-nutritive sucking is the most frequently studied non-pharmacological intervention for procedural pain relief in neonates.

Objectives: To determine the efficacy, effect of dose, method of administration and safety of sucrose for relieving procedural pain in neonates as assessed by validated composite pain scores, physiological pain indicators (heart rate, respiratory rate, saturation of peripheral oxygen in the blood, transcutaneous oxygen and carbon dioxide (gas exchange measured across the skin - TcpO2, TcpCO2), near infrared spectroscopy (NIRS), electroencephalogram (EEG), or behavioural pain indicators (cry duration, proportion of time crying, proportion of time facial actions (e.g. grimace) are present), or a combination of these and long-term neurodevelopmental outcomes.

Search methods: We used the standard methods of the Cochrane Neonatal. We performed electronic and manual literature searches in February 2016 for published randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 1, 2016), MEDLINE (1950 to 2016), EMBASE (1980 to 2016), and CINAHL (1982 to 2016). We did not impose language restrictions.

Selection criteria: RCTs in which term or preterm neonates (postnatal age maximum of 28 days after reaching 40 weeks' postmenstrual age), or both, received sucrose for procedural pain. Control interventions included no treatment, water, glucose, breast milk, breastfeeding, local anaesthetic, pacifier, positioning/containing or acupuncture.

Data collection and analysis: Our main outcome measures were composite pain scores (including a combination of behavioural, physiological and contextual indicators). Secondary outcomes included separate physiological and behavioural pain indicators. We reported a mean difference (MD) or weighted MD (WMD) with 95% confidence intervals (CI) using the fixed-effect model for continuous outcome measures. For categorical data we used risk ratio (RR) and risk difference. We assessed heterogeneity by the I(2) test. We assessed the risk of bias of included trials using the Cochrane 'Risk of bias' tool, and assessed the quality of the evidence using the GRADE system.

Main results: Seventy-four studies enrolling 7049 infants were included. Results from only a few studies could be combined in meta-analyses and for most analyses the GRADE assessments indicated low- or moderate-quality evidence. There was high-quality evidence for the beneficial effect of sucrose (24%) with non-nutritive sucking (pacifier dipped in sucrose) or 0.5 mL of sucrose orally in preterm and term infants: Premature Infant Pain Profile (PIPP) 30 s after heel lance WMD -1.70 (95% CI -2.13 to -1.26; I(2) = 0% (no heterogeneity); 3 studies, n = 278); PIPP 60 s after heel lance WMD -2.14 (95% CI -3.34 to -0.94; I(2) = 0% (no heterogeneity; 2 studies, n = 164). There was high-quality evidence for the use of 2 mL 24% sucrose prior to venipuncture: PIPP during venipuncture WMD -2.79 (95% CI -3.76 to -1.83; I(2) = 0% (no heterogeneity; 2 groups in 1 study, n = 213); and intramuscular injections: PIPP during intramuscular injection WMD -1.05 (95% CI -1.98 to -0.12; I(2) = 0% (2 groups in 1 study, n = 232). Evidence from studies that could not be included in RevMan-analyses supported these findings. Reported adverse effects were minor and similar in the sucrose and control groups. Sucrose is not effective in reducing pain from circumcision. The effectiveness of sucrose for reducing pain/stress from other interventions such as arterial puncture, subcutaneous injection, insertion of nasogastric or orogastric tubes, bladder catherization, eye examinations and echocardiography examinations are inconclusive. Most trials indicated some benefit of sucrose use but that the evidence for other painful procedures is of lower quality as it is based on few studies of small sample sizes. The effects of sucrose on long-term neurodevelopmental outcomes are unknown.

Authors' conclusions: Sucrose is effective for reducing procedural pain from single events such as heel lance, venipuncture and intramuscular injection in both preterm and term infants. No serious side effects or harms have been documented with this intervention. We could not identify an optimal dose due to inconsistency in effective sucrose dosage among studies. Further investigation of repeated administration of sucrose in neonates is needed. There is some moderate-quality evidence that sucrose in combination with other non-pharmacological interventions such as non-nutritive sucking is more effective than sucrose alone, but more research of this and sucrose in combination with pharmacological interventions is needed. Sucrose use in extremely preterm, unstable, ventilated (or a combination of these) neonates needs to be addressed. Additional research is needed to determine the minimally effective dose of sucrose during a single painful procedure and the effect of repeated sucrose administration on immediate (pain intensity) and long-term (neurodevelopmental) outcomes.

PubMed Disclaimer

Conflict of interest statement

Bonnie Stevens ‐ is an author of the following included trials: Gibbins 2002; Johnston 1997; Mitchell 2004; Stevens 1999; Stevens 2005a. For these trials two authors (SH, AS) did the data abstraction and RoB assessments. No other conflict of interest to declare

Janet Yamada ‐ is an author of the following included trial: Stevens 2005a. For this trial two other authors (SH, AS) did the data abstraction and RoB assessments. No other conflict of interest to declare.

Arne Ohlsson ‐ ‐ is an author of the following included trial: Gibbins 2002. For this trial two other authors (SH, AS) did the data abstraction and RoB assessments. No other conflict of interest to declare.

Sarah Haliburton ‐ No conflict of interest to declare

Allyson Shorkey ‐ No conflict of interest to declare

Figures

1
1
Study flow diagram: review update
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 6 Heel lance: Sucrose (24%) + NNS vs. water + NNS, outcome: 6.2 PIPP 30 s after heel lance (term and preterm infants).
5
5
Forest plot of comparison: 6 Heel lance: Sucrose (24%) + NNS vs. water + NNS, outcome: 6.3 PIPP 60 s after heel lance.
6
6
Forest plot of comparison: 18 Venipuncture: sucrose (24% to 30%) versus control (sterile water or no treatment), outcome: 18.1 PIPP score during venipuncture.
7
7
Forest plot of comparison: 23 Intramuscular injection (term infants): Sucrose (20‐25%) vs. water or no intervention, outcome: 23.2 PIPP during IM injection (term infants).
8
8
Forest plot of comparison: 30 ROP examination: sucrose (24% to 33%) (sucrose or sucrose + NNS) versus control (water or water + NNS), outcome: 30.1 PIPP score during eye examination.
1.1
1.1. Analysis
Comparison 1 Heel lance (term infants): sucrose (12% to 12.5%) versus water/routine care, Outcome 1 Total crying time (s).
1.2
1.2. Analysis
Comparison 1 Heel lance (term infants): sucrose (12% to 12.5%) versus water/routine care, Outcome 2 Percentage change in heart rate 1 min after heel lance.
2.1
2.1. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 1 PIPP at 30 s after heel lance.
2.2
2.2. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 2 PIPP at 60 s after heel lance.
2.3
2.3. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 3 PIPP score during heel lance (1st heel lance).
2.4
2.4. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 4 DAN score at 30 s after heel lance.
2.5
2.5. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 5 NIPS during heel lance.
2.6
2.6. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 6 Duration of first cry (s).
2.7
2.7. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 7 Total crying time.
2.8
2.8. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 8 Heart rate (beats/min) during heel lance.
2.9
2.9. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 9 Percentage change in heart rate 1 min after heel lance.
2.10
2.10. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 10 Respiratory rate (breaths/min) during heel lance.
2.11
2.11. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 11 Oxygen saturation (%) during heel lance.
2.12
2.12. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 12 Skin blood flow during heel lance (perfusion units (PU)).
2.13
2.13. Analysis
Comparison 2 Heel lance: sucrose (20% to 33%) versus water, Outcome 13 Nociceptive‐specific brain activity (mean weight).
3.1
3.1. Analysis
Comparison 3 Heel lance: sucrose (50%) versus water, Outcome 1 Duration of first cry (s).
3.2
3.2. Analysis
Comparison 3 Heel lance: sucrose (50%) versus water, Outcome 2 Percentage change in heart rate 1 min after heel lance.
4.1
4.1. Analysis
Comparison 4 Heel lance: sucrose (24%) versus breastfeeding, Outcome 1 PIPP.
4.2
4.2. Analysis
Comparison 4 Heel lance: sucrose (24%) versus breastfeeding, Outcome 2 Comfort score.
5.1
5.1. Analysis
Comparison 5 Heel lance: sucrose (24%) + NNS versus water + NNS, or pacifier dipped in sucrose versus pacifier dipped in water, Outcome 1 NFCS.
5.2
5.2. Analysis
Comparison 5 Heel lance: sucrose (24%) + NNS versus water + NNS, or pacifier dipped in sucrose versus pacifier dipped in water, Outcome 2 PIPP 30 s after heel lance (mainly preterm infants).
5.3
5.3. Analysis
Comparison 5 Heel lance: sucrose (24%) + NNS versus water + NNS, or pacifier dipped in sucrose versus pacifier dipped in water, Outcome 3 PIPP 60 s after heel lance.
5.4
5.4. Analysis
Comparison 5 Heel lance: sucrose (24%) + NNS versus water + NNS, or pacifier dipped in sucrose versus pacifier dipped in water, Outcome 4 Crying time (s).
6.1
6.1. Analysis
Comparison 6 Heel lance: sucrose (20%) versus human milk, Outcome 1 Crying time (s).
7.1
7.1. Analysis
Comparison 7 Heel lance: sucrose (24%) + NNS+ NIDCAP support versus breast milk (by breastfeeding), Outcome 1 PIPP score.
7.2
7.2. Analysis
Comparison 7 Heel lance: sucrose (24%) + NNS+ NIDCAP support versus breast milk (by breastfeeding), Outcome 2 COMFORTneo score.
8.1
8.1. Analysis
Comparison 8 Heel lance: sucrose (24%) + NNS + NIDCAP support versus breast milk (by syringe), Outcome 1 PIPP score.
8.2
8.2. Analysis
Comparison 8 Heel lance: sucrose (24%) + NNS + NIDCAP support versus breast milk (by syringe), Outcome 2 COMFORTneo score.
9.1
9.1. Analysis
Comparison 9 Repeated heel lances: sucrose (20%) versus facilitated tucking, Outcome 1 Total Bernese Pain Scale for Neonates during heel lance.
9.2
9.2. Analysis
Comparison 9 Repeated heel lances: sucrose (20%) versus facilitated tucking, Outcome 2 Total Bernese Pain Scale for Neonates during recovery.
10.1
10.1. Analysis
Comparison 10 Repeated heel lances: sucrose (20%) versus facilitated tucking + sucrose (20%), Outcome 1 Total Bernese Pain Scale for Neonates during heel lance (preterm infants).
10.2
10.2. Analysis
Comparison 10 Repeated heel lances: sucrose (20%) versus facilitated tucking + sucrose (20%), Outcome 2 Total Bernese Pain Scale for Neonates during recovery (preterm infants).
11.1
11.1. Analysis
Comparison 11 Heel lance: sucrose (30% to 33%) versus glucose (30% to 33%), Outcome 1 Heart rate (beats/min) during heel lance.
11.2
11.2. Analysis
Comparison 11 Heel lance: sucrose (30% to 33%) versus glucose (30% to 33%), Outcome 2 Crying time (s).
11.3
11.3. Analysis
Comparison 11 Heel lance: sucrose (30% to 33%) versus glucose (30% to 33%), Outcome 3 Percentage change in heart rate 1 min after heel lance.
12.1
12.1. Analysis
Comparison 12 Heel lance: sucrose (50%) versus glucose (50%), Outcome 1 Heart rate (beats/min) during heel lance.
13.1
13.1. Analysis
Comparison 13 Heel lance (term infants): sucrose (24%) versus laser acupuncture, Outcome 1 NIPS score.
13.2
13.2. Analysis
Comparison 13 Heel lance (term infants): sucrose (24%) versus laser acupuncture, Outcome 2 Crying time (s).
14.1
14.1. Analysis
Comparison 14 Heel lance: sucrose (24%) versus sucrose (24%) + NNS, Outcome 1 Revised NFCS.
14.2
14.2. Analysis
Comparison 14 Heel lance: sucrose (24%) versus sucrose (24%) + NNS, Outcome 2 Percentage increase in heart rate.
14.3
14.3. Analysis
Comparison 14 Heel lance: sucrose (24%) versus sucrose (24%) + NNS, Outcome 3 Decrease in oxygen saturation in blood (%).
15.1
15.1. Analysis
Comparison 15 Heel lance: sucrose (24%) versus sucrose (24%) + swaddling, Outcome 1 Revised NFCS.
15.2
15.2. Analysis
Comparison 15 Heel lance: sucrose (24%) versus sucrose (24%) + swaddling, Outcome 2 Percentage increase in heart rate.
15.3
15.3. Analysis
Comparison 15 Heel lance: sucrose (24%) versus sucrose (24%) + swaddling, Outcome 3 Decrease in oxygen saturation in blood (%).
16.1
16.1. Analysis
Comparison 16 Heel lance: sucrose (24%) versus sucrose (24%) + NNS + swaddling, Outcome 1 Revised NFCS.
16.2
16.2. Analysis
Comparison 16 Heel lance: sucrose (24%) versus sucrose (24%) + NNS + swaddling, Outcome 2 Percentage increase in heart rate.
16.3
16.3. Analysis
Comparison 16 Heel lance: sucrose (24%) versus sucrose (24%) + NNS + swaddling, Outcome 3 Decrease in oxygen saturation in blood (%).
17.1
17.1. Analysis
Comparison 17 Venipuncture: sucrose (12%) versus water, Outcome 1 NIPS score in term and preterm infants.
18.1
18.1. Analysis
Comparison 18 Venipuncture: sucrose (24% to 30%) versus control (sterile water or no treatment), Outcome 1 PIPP score during venipuncture.
18.2
18.2. Analysis
Comparison 18 Venipuncture: sucrose (24% to 30%) versus control (sterile water or no treatment), Outcome 2 Duration of cry (s).
19.1
19.1. Analysis
Comparison 19 Venipuncture: sucrose (50%) versus water, Outcome 1 Duration of first cry (s).
20.1
20.1. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 1 PIPP score.
20.2
20.2. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 2 PIPP score during recovery period.
20.3
20.3. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 3 DAN score during venipuncture.
20.4
20.4. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 4 DAN score during recovery period.
20.5
20.5. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 5 Facial grimacing score.
20.6
20.6. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 6 Observer‐rated pain (VAS) (cm).
20.7
20.7. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 7 Mean crying times during all procedures (s).
20.8
20.8. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 8 Heart rate (beats/min).
20.9
20.9. Analysis
Comparison 20 Venipuncture: sucrose (24% to 30%) versus sucrose (24% to 30%) + EMLA/Liposomal lidocaine cream on the skin, Outcome 9 Oxygen saturation %.
21.1
21.1. Analysis
Comparison 21 Venipuncture: sucrose (24%) versus liposomal lidocaine, Outcome 1 Facial grimacing score.
21.2
21.2. Analysis
Comparison 21 Venipuncture: sucrose (24%) versus liposomal lidocaine, Outcome 2 Observer‐rated pain (VAS) (cm).
21.3
21.3. Analysis
Comparison 21 Venipuncture: sucrose (24%) versus liposomal lidocaine, Outcome 3 Cry duration (s).
21.4
21.4. Analysis
Comparison 21 Venipuncture: sucrose (24%) versus liposomal lidocaine, Outcome 4 Heart rate (beats/min).
21.5
21.5. Analysis
Comparison 21 Venipuncture: sucrose (24%) versus liposomal lidocaine, Outcome 5 Oxygen saturation (%).
22.1
22.1. Analysis
Comparison 22 Arterial puncture in preterm infants: sucrose (24%) versus no intervention, Outcome 1 Heart rate (beats/min) after needle insertion.
22.2
22.2. Analysis
Comparison 22 Arterial puncture in preterm infants: sucrose (24%) versus no intervention, Outcome 2 Heart rate (beats/min) 1 min after procedure completed.
22.3
22.3. Analysis
Comparison 22 Arterial puncture in preterm infants: sucrose (24%) versus no intervention, Outcome 3 Oxygen saturation in blood (%) after needle insertion.
22.4
22.4. Analysis
Comparison 22 Arterial puncture in preterm infants: sucrose (24%) versus no intervention, Outcome 4 Oxygen saturation in blood (%) 1 min after procedure.
23.1
23.1. Analysis
Comparison 23 Intramuscular injection (term infants): sucrose (20% to 25%) versus water or no intervention, Outcome 1 NIPS 1 min to 2 min after IM injection.
23.2
23.2. Analysis
Comparison 23 Intramuscular injection (term infants): sucrose (20% to 25%) versus water or no intervention, Outcome 2 PIPP during IM injection (term infants).
23.3
23.3. Analysis
Comparison 23 Intramuscular injection (term infants): sucrose (20% to 25%) versus water or no intervention, Outcome 3 Duration of cry (s).
24.1
24.1. Analysis
Comparison 24 Intramuscular injection (term infants): sucrose (25%) versus glucose (25%), Outcome 1 NIPS 1 min to 2 min after immunization.
25.1
25.1. Analysis
Comparison 25 Intramuscular injection (term infants): sucrose (25%) versus sucrose (25%) + warmth, Outcome 1 Crying time (s).
25.2
25.2. Analysis
Comparison 25 Intramuscular injection (term infants): sucrose (25%) versus sucrose (25%) + warmth, Outcome 2 Grimacing time.
26.1
26.1. Analysis
Comparison 26 Bladder catheterization: sucrose (24%) versus sterile water, Outcome 1 Change in DAN score.
26.2
26.2. Analysis
Comparison 26 Bladder catheterization: sucrose (24%) versus sterile water, Outcome 2 Infants crying at maximal catheter insertion.
27.1
27.1. Analysis
Comparison 27 Orogastric tube insertion in preterm infants: sucrose (24%) versus distilled water, Outcome 1 PIPP score intra procedure.
27.2
27.2. Analysis
Comparison 27 Orogastric tube insertion in preterm infants: sucrose (24%) versus distilled water, Outcome 2 PIPP score 30 s post procedure.
27.3
27.3. Analysis
Comparison 27 Orogastric tube insertion in preterm infants: sucrose (24%) versus distilled water, Outcome 3 PIPP score 1 min post procedure.
28.1
28.1. Analysis
Comparison 28 ROP examination: sucrose (24%) by syringe + swaddled + pacifier versus water by syringe + swaddled + pacifier, Outcome 1 PIPP during examination.
28.2
28.2. Analysis
Comparison 28 ROP examination: sucrose (24%) by syringe + swaddled + pacifier versus water by syringe + swaddled + pacifier, Outcome 2 Crying time (%).
28.3
28.3. Analysis
Comparison 28 ROP examination: sucrose (24%) by syringe + swaddled + pacifier versus water by syringe + swaddled + pacifier, Outcome 3 Heart rate (beats/min).
28.4
28.4. Analysis
Comparison 28 ROP examination: sucrose (24%) by syringe + swaddled + pacifier versus water by syringe + swaddled + pacifier, Outcome 4 Mean blood pressure (mmHg).
28.5
28.5. Analysis
Comparison 28 ROP examination: sucrose (24%) by syringe + swaddled + pacifier versus water by syringe + swaddled + pacifier, Outcome 5 Respiratory rate (breaths/min).
28.6
28.6. Analysis
Comparison 28 ROP examination: sucrose (24%) by syringe + swaddled + pacifier versus water by syringe + swaddled + pacifier, Outcome 6 Oxygen saturation (%).
29.1
29.1. Analysis
Comparison 29 ROP examination: sucrose (24% ) + swaddled + held versus lying in the crib, Outcome 1 Total crying time.
29.2
29.2. Analysis
Comparison 29 ROP examination: sucrose (24% ) + swaddled + held versus lying in the crib, Outcome 2 Oxygen saturation (%) during examination.
30.1
30.1. Analysis
Comparison 30 ROP examination: sucrose (24% to 33%) (sucrose or sucrose + NNS) versus control (water or water + NNS), Outcome 1 PIPP score during eye examination.
30.2
30.2. Analysis
Comparison 30 ROP examination: sucrose (24% to 33%) (sucrose or sucrose + NNS) versus control (water or water + NNS), Outcome 2 Crying time (s) during eye examination.
31.1
31.1. Analysis
Comparison 31 Circumcision: sucrose 50% solution on a premature nipple containing a 2 x 2 cm sterile gauze pad moistened by the fluid versus no treatment, Outcome 1 Change from baseline in heart rate (beats/min).
32.1
32.1. Analysis
Comparison 32 Circumcision: sucrose (24%) versus EMLA, Outcome 1 N‐PASS score during circumcision.
32.2
32.2. Analysis
Comparison 32 Circumcision: sucrose (24%) versus EMLA, Outcome 2 N‐PASS score after 5 min.
32.3
32.3. Analysis
Comparison 32 Circumcision: sucrose (24%) versus EMLA, Outcome 3 Heart rate (beats/min) during circumcision.
32.4
32.4. Analysis
Comparison 32 Circumcision: sucrose (24%) versus EMLA, Outcome 4 Respiratory rate (cycles/min) during circumcision.
32.5
32.5. Analysis
Comparison 32 Circumcision: sucrose (24%) versus EMLA, Outcome 5 Oxygen saturation (%) during circumcision.
33.1
33.1. Analysis
Comparison 33 Circumcision: sucrose (24%) versus EMLA + sucrose (24%), Outcome 1 N‐PASS score during circumcision.
33.2
33.2. Analysis
Comparison 33 Circumcision: sucrose (24%) versus EMLA + sucrose (24%), Outcome 2 N‐PASS score after 5 min.
33.3
33.3. Analysis
Comparison 33 Circumcision: sucrose (24%) versus EMLA + sucrose (24%), Outcome 3 Heart rate (beats/min) during circumcision.
33.4
33.4. Analysis
Comparison 33 Circumcision: sucrose (24%) versus EMLA + sucrose (24%), Outcome 4 Respiratory rate (cycles/min).
33.5
33.5. Analysis
Comparison 33 Circumcision: sucrose (24%) versus EMLA + sucrose (24%), Outcome 5 Oxygen saturation (%) during circumcision.
34.1
34.1. Analysis
Comparison 34 Circumcision: sucrose solution (50%) on a premature nipple containing a 2 x 2 cm sterile gauze pad moistened by the fluid versus dorsal penile nerve block (DPNB), Outcome 1 Change in heart rate (beats/min) from baseline.
35.1
35.1. Analysis
Comparison 35 Circumcision: pacifier dipped in sucrose (24%) + DPNB versus pacifier dipped in water + DPNB, Outcome 1 Mean Behavioral Distress Scale scores during circumcision.
35.2
35.2. Analysis
Comparison 35 Circumcision: pacifier dipped in sucrose (24%) + DPNB versus pacifier dipped in water + DPNB, Outcome 2 Mean plasma cortisol levels n mol/dL.
36.1
36.1. Analysis
Comparison 36 Echocardiography (term and preterm infants): sucrose (24%) versus no medication/placebo, Outcome 1 PIPP.
37.1
37.1. Analysis
Comparison 37 Potentially painful procedures over seven days: sucrose (24%) versus water, Outcome 1 'Motor development and vigor' (MDV) domain of NAPI tool.
37.2
37.2. Analysis
Comparison 37 Potentially painful procedures over seven days: sucrose (24%) versus water, Outcome 2 'Alertness and orientation' (AO) domain of NAPI.
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Update of

References

References to studies included in this review

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Boyle 2006 {published data only}
    1. Boyle EM, Freer Y, Khan‐Orakzai, Watkinson M, Wright E, Ainsworth JR, et al. Sucrose and non‐nutritive sucking for the relief of pain in screening for retinopathy of prematurity: a randomized controlled trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2006;91:F166‐8. - PMC - PubMed
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    1. Bucher H‐U, Moser T, Siebenthal K, Keel M, Wolf M, Duc G. Sucrose reduces pain reaction to heel lancing in preterm infants: a placebo‐controlled, randomized and masked study. Pediatric Research 1995;38:332‐5. - PubMed
Carbajal 1999 {published data only}
    1. Carbajal R, Chauvet X, Couderc SD, Olivier‐Martin M. Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. BMJ 1999;319:1393‐7. - PMC - PubMed
Cignacco 2012 {published data only}
    1. Cignacco EL, Sellam G, Stoffel L, Gerull R, Nelle M, Anand KJ, et al. Oral sucrose and "facilitated tucking" for repeated pain relief in preterms: a randomized controlled trial. Pediatrics 2012;129(2):299‐308. [PUBMED: 22232305] - PubMed
    1. Gerull R, Cignacco E, Stoffel L, Sellam G, Nelle M. Physiological parameters after nonpharmacological analgesia in preterm infants: a randomized trial. Acta Pædiatrica 2013;102(8):e368–73. [PUBMED: 23651076] - PubMed
Codipietro 2008 {published data only}
    1. Codipietro L, Ceccarelli M, Ponzone A. Breastfeeding or oral sucrose solution in term neonates receiving heel lance: a randomized controlled trial. Pediatrics 2008;122:e716‐21. - PubMed
Dilli 2014 {published data only}
    1. Dilli D, Ilarslan NE, Kabatas EU, Zenciroglu A, Simsek Y, Okumus N. Oral sucrose and non‐nutritive sucking goes some way to reducing pain during retinopathy of prematurity eye examinations. Acta Paediatrica 2014;103(2):e76‐9. [PUBMED: 24730361] - PubMed
Elserafy 2009 {published data only}
    1. Elserafy FA, Alsaedi SA, Louwrens J, Bin Sadiq B, Mersal AY. Oral sucrose and a pacifier for pain relief during simple procedures in preterm infants: a randomized controlled trial. Annals of Saudi Medicine 2009;29(3):184‐8. [PUBMED: 19448377] - PMC - PubMed
Gal 2005 {published data only}
    1. Gal P, Kissling GE, Young WO, Dunaway KK, Marsh VA, Jones SM, et al. Efficacy of sucrose to reduce pain in premature infants during eye examinations for retinopathy of prematurity. Annals of Pharmacotherapy 2005;39:1029‐33. - PubMed
Gaspardo 2008 {published data only}
    1. Gaspardo CM, Miyase CI, Chimello JT, Martinez FE, Martins Linhares MB. Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates?. Pain 2008;137:16‐25. - PubMed
Gibbins 2002 {published and unpublished data}
    1. Gibbins S. Efficacy and Safety of Sucrose for Procedural Pain Relief in Preterm and Term Neonates [PhD Thesis]. Toronto: University of Toronto, 2001. - PubMed
    1. Gibbins S, Stevens B. The influence of gestational age on the efficacy and short‐term safety of sucrose for procedural pain relief. Advances in Neonatal Care 2003;3:241‐9. - PubMed
    1. Gibbins S, Stevens B, Hodnett E, Pinelli J, Ohlsson A, Darlington G. Efficacy and safety of sucrose for procedural pain relief in preterm and term neonates. Nursing Research 2002;51:375‐82. - PubMed
Gormally 2001 {published data only}
    1. Gormally S, Barr RG, Wertheim L, Alkawaf R, Calinoiu N, Young SN. Contact and nutrient caregiving effects on newborn infant pain responses. Developmental Medicine and Child Neurology 2001;43:28‐38. - PubMed
Grabska 2005 {published data only}
    1. Grabska J, Walden P, Lerer T, Kelly C, Hussain N, Donovan T, et al. Can oral sucrose reduce the pain and distress associated with screening for retinopathy for prematurity?. Journal of Perinatology 2005;25:33‐5. - PubMed
Gray 2012 {published data only}
    1. Gray L, Lang CW, Porges SW. Warmth is analgesic in healthy newborns. Pain 2012;153(5):960‐6. [PUBMED: 22424877] - PMC - PubMed
Gray 2015 {published data only}
    1. Gray L, Garza E, Zageris D, Heilman KJ, Porges SW. Sucrose and warmth for analgesia in healthy newborns: an RCT. Pediatrics 2015;135(3):e607‐14. [PUBMED: 25687147] - PMC - PubMed
Greenberg 2002 {published data only}
    1. Greenberg CS. A sugar‐coated pacifier reduces procedural pain in newborns. Pediatric Nursing 2002;28:271‐7. - PubMed
Guala 2001 {published data only}
    1. Guala A, Pastore G, Liverani ME, Giroletti G, Gulino F, Meriggi AI, et al. Glucose or sucrose as an analgesic for newborns: a randomized controlled blind trial. Minerva Pediatrica 2001;53:271‐4. - PubMed
Haouari 1995 {published data only}
    1. Haouari N, Wood C, Griffiths G, Levene M. The analgesic effect of sucrose in full term infants: a randomised controlled trial. BMJ 1995;310:1498‐500. - PMC - PubMed
Harrison 2003 {published data only}
    1. Harrison D, Johnston L, Loughnan P. Oral sucrose for procedural pain in sick hospitalized infants: a randomized‐controlled trial. Journal of Paediatric and Child Health 2003;39:591‐7. - PubMed
Herschel 1998 {published data only}
    1. Herschel M, Khoshnood B, Ellman C, Maydew N, Mittendorf R. Neonatal circumcision. Randomized trial of sucrose pacifier for pain control. Archives of Pediatrics and Adolescent Medicine 1998;152:279‐84. - PubMed
Isik 2000a {published data only}
    1. Isik U, Ozek E, Bilgen H, Cebeci D. Comparison of oral glucose and sucrose solutions on pain response in neonates. Journal of Pain 2000;1:275‐8. - PubMed
Johnston 1997 {published data only}
    1. Johnston CC, Stremler RL, Stevens BJ, Horton LJ. Effectiveness of oral sucrose and simulated rocking on pain response in preterm neonates. Pain 1997;72:193‐9. - PubMed
Johnston 1999 {published data only}
    1. Johnston CC, Stremler R, Horton L, Friedman A. Effect of repeated doses of sucrose during heel stick procedure in preterm neonates. Biology of the Neonate 1999;75:160‐6. - PubMed
Johnston 2002 {published data only}
    1. Boyer K, Johnston C, Walker CD, Filion F, Sherrard A. Does sucrose analgesia promote physiological stability in preterm neonates?. Biology of the Neonate 2004;85(1):26‐31. [PUBMED: 14631163] - PubMed
    1. Johnston CC, Filion F, Snider L, Majnemer A, Limperopolous C, Walker CD, et al. Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks' postconceptional age. Pediatrics 2002;110:523‐8. - PubMed
Kaufman 2002 {published data only}
    1. Kaufman GE, Cimo S, Miller LW, Blass EM. An evaluation of the effects of sucrose on neonatal pain with 2 commonly used circumcision methods. American Journal of Obstetrics and Gynecology 2002;186:564‐8. - PubMed
Kristoffersen 2011 {published data only}
    1. Kristoffersen L, Skogvoll E, Hafström M. Pain reduction on insertion of a feeding tube in preterm infants: a randomized controlled trial. Pediatrics 2011;127:e1449‐54. - PubMed
Leng 2013 {published data only}
    1. Leng HY, Zheng XL, Yan L, Zhang XH, He HY, Xiang M. [Effects of different types and concentration of oral sweet solution on reducing neonatal pain during heel lance procedures]. Zhonghua er ke za zhi. Chinese Journal of Pediatrics 2013;51(9):654‐8. [PUBMED: 24330983] - PubMed
Leng 2015 {published data only}
    1. Leng HY, Zheng XL, Zhang XH, He HY, Tu GF, Fu Q. Combined non‐pharmacological interventions for newborn pain relief in two degrees of pain procedures: a randomized clinical trial. European Journal of Pain 2016;20(6):989‐97. [PUBMED: 26685099] - PubMed
Liaw 2011 {published data only}
    1. Liaw J‐J, Zeng W‐P, Yang L, Yuh Y‐S, Yin T, Yang M‐H. Nonnutritive sucking and oral sucrose relieve neonatal pain during intramuscular injection of hepatitis vaccine. Journal of Pain and Symptom Management 2011;42(6):918‐30. [PUBMED: 21620644] - PubMed
Liaw 2013 {published data only}
    1. Liaw JJ, Yang L, Lee CM, Fan HC, Chang YC, Cheng LP. Effects of combined use of non‐nutritive sucking, oral sucrose, and facilitated tucking on infant behavioural states across heel‐stick procedures: a prospective, randomised controlled trial. International Journal of Nursing Studies 2013;50(7):883‐94. [PUBMED: 23068310] - PubMed
    1. Yin T, Yang L, Lee T‐Y, Li C‐C, Hua Y‐M, Liaw J‐J. Development of atraumatic heel‐stick procedures by combined treatment with non‐nutritive sucking, oral sucrose, and facilitated tucking: a randomised, controlled trial. International Journal of Nursing Studies 2015;52(8):1288‐99. [PUBMED: 25939641] - PubMed
Marin Gabriel 2013 {published data only}
    1. Marin Gabriel MA, Rey Hurtado de Mendoza B, Jimenez Figueroa L, Medina V, Iglesias Fernandez B, Vazquez Rodriguez M, et al. Analgesia with breastfeeding in addition to skin‐to‐skin contact during heel prick. Archives of Disease in Childhood. Fetal and neonatal edition 2013;98(6):F499‐503. [PUBMED: 23839984] - PubMed
Mathai 2006 {published data only}
    1. Mathai S, Natrajan N, Rajalakshmi NR. A comparative study of non‐pharmacological methods to reduce pain in neonates. Indian Pediatrics 2006;43:1070‐5. - PubMed
McCullough 2008 {published data only}
    1. McCullough S, Halton T, Mowbray D, Macfarlane PI. Lingual sucrose reduces the pain response to nasogastric tube insertion: a randomised clinical trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93:F100‐3. - PubMed
Milazzo 2011 {published data only}
    1. Milazzo W, Fielder J, Bittel A, Coil J, McClure M, Tobin P, et al. Oral sucrose to decrease pain associated with arterial puncture in infants 30 to 36 weeks’ gestation. A randomized clinical trial. Advances in Neonatal Care 2011;11(6):406‐11. [PUBMED: 22123473] - PubMed
Mitchell 2004 {published data only}
    1. Mitchell A, Stevens B, Mungan N, Johnson W, Lobert S, Boss B. Analgesic effects of oral sucrose and pacifier during eye examinations for retinopathy of prematurity. Pain Management Nursing 2004;5:160‐8. - PubMed
Montoya 2009 {published data only}
    1. Montoya IG, Gázquez MAR, Cadavid LAM, Jaramillo AQ. [The use of sucrose for the prevention of pain during venipuncture in neonates]. Enfermería Clínica 2009;19:267‐74. - PubMed
Mucignat 2004 {published data only}
    1. Mucignat V, Ducrocq S, Lebas F, Mochel F, Baudon JJ, Gold F. Analgesic effects of EMLA cream and saccharose solution for subcutaneous injections in preterm newborns: a prospective study of 265 injections [Effet analgésique de la crème EMLA®, du saccharose et de leur association pour les injections sous‐cutanées chez le nouveau‐né prématuré: étude prospective de 265 injections]. Archives de Pédiatrie 2004;11:921‐25. - PubMed
O'Sullivan 2010 {published data only}
    1. O'Sullivan A, O'Connor M, Brosnahan D, McCreery K, Dempsey EM. Sweeten, soother and swaddle for retinopathy of prematurity screening: a randomised placebo controlled trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2010;95:F419–22. - PubMed
Ogawa 2005 {published data only}
    1. Ogawa S, Ogihara T, Fujiwara E, Ito K, Nakano M, Nakayama S, et al. Venepuncture is preferable to heel lance for blood sampling in term neonates. Archives of Disease in Childhood. Fetal and Neonatal Edition 2005;90:F432‐6. - PMC - PubMed
Okan 2007 {published data only}
    1. Okan F, Coban A, Ince Z, Yapici Z, Can G. Analgesia in preterm newborns: the comparative effects of sucrose and glucose. European Journal of Pediatrics 2007;166:1017‐24. - PubMed
    1. Ozdogan T, Akman I, Cebeci D, Bilgen H, Ozek E. Comparison of two doses of breast milk and sucrose during neonatal heel prick. Pediatrics International 2010;52:175‐9. - PubMed
Örs 1999 {published data only}
    1. Örs R, Özek E, Baysoy G, Cebeci D, Bilgen H, Türküner M, et al. Comparison of sucrose and human milk on pain response in newborns. European Journal of Pediatrics 1999;158:63‐6. - PubMed
Overgaard 1999 {published data only}
    1. Overgaard C, Knudesen A. Pain‐relieving effect of sucrose in newborns during heel prick. Biology of the Neonate 1999;75:279‐84. - PubMed
Pandey 2013 {published data only}
    1. Pandey M, Datta V, Rehan HS. Role of sucrose in reducing painful response to orogastric tube insertion in preterm neonates. Indian Journal of Pediatrics 2013;80(6):476‐82. [PUBMED: 23263970] - PubMed
Potana 2015 {published data only}
    1. Potana NT, Dongara AR, Nimbalkar SM, Patel DV, Nimbalkar AS, Phatak A. Oral sucrose for pain in neonates during echocardiography: a randomized controlled trial. Indian Pediatrics 2015;52(6):493‐7. - PubMed
Ramenghi 1996a {published data only}
    1. Ramenghi LA, Wood CM, Griffith GC, Levene MI. Reduction of pain response in premature infants using intraoral sucrose. Archives of Disease in Childhood. Fetal and Neonatal Edition 1996;74:F126‐8. - PMC - PubMed
Ramenghi 1996b {published data only}
    1. Ramenghi LA, Griffith GC, Wood CM, Levene MI. Effect of non‐sucrose sweet tasting solution on neonatal heel prick responses. Archives of Disease in Childhood. Fetal and Neonatal Edition 1996;74:F129‐31. - PMC - PubMed
Ramenghi 1999 {published data only}
    1. Ramenghi LA, Evans DJ, Levene MI. "Sucrose analgesia": absorptive mechanism or taste perception?. Archives of Disease in Childhood. Fetal and Neonatal Edition 1999;80:F146‐7. - PMC - PubMed
Rogers 2006 {published data only}
    1. Rogers AJ, Greenwald MH, DeGuzman MA, Kelly ME, Simon HK. A randomized, controlled trial of sucrose analgesia in infants younger than 90 days of age who require bladder catheterization in pediatric emergency department. Academic Emergency Medicine 2006;13:617‐22. - PubMed
Rush 2005 {published data only}
    1. Rush R, Rush S, Ighani F, Anderson B, Irwin M, Naqvi M. The effects of comfort care on the pain responses in preterm infants undergoing screening for retinopathy of prematurity. Retina 2005;25:59‐62. - PubMed
Rushforth 1993 {published data only}
    1. Rushforth JA, Levene MI. Effect of sucrose on crying in response to heel stab. Archives of Disease in Childhood 1993;69:388‐9. - PMC - PubMed
Simonse 2012 {published data only}
    1. Simonse E, Mulder PG, Beek RH. Analgesic effect of breast milk versus sucrose for analgesia during heel lance in late preterm infants. Pediatrics 2012;129(4):657‐63. [PUBMED: 22392168] - PubMed
Slater 2010 {published and unpublished data}
    1. Slater R, Cornelissen L, Fabrizi L, Patten D, Yoxen J, Worley A, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. The Lancet 2010;376:1225‐32. - PMC - PubMed
Stang 1997 {published data only}
    1. Stang HJ, Snellman LW, Condon LM, Conroy MM, Liebo R, Brodersen L, et al. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics 1997;100:E3. - PubMed
Stevens 1999 {published data only}
    1. Johnston CC, Sherrard A, Stevens B, Franck L, Stremler R, Jack A. Do cry features reflect pain intensity in preterm neonates?. Biology of the Neonate 1999;76:120‐4. - PubMed
    1. Stevens B, Johnston C, Franck P, Petryshen P, Jack A, Foster G. The efficacy of developmentally sensitive interventions and sucrose for relieving pain in very low birth weight infants. Nursing Research 1999;48:35‐43. - PubMed
Stevens 2005a {published data only}
    1. Stevens B, Yamada J, Beyene J, Gibbins S, Petryshen P, Stinson J, et al. Consistent management of repeated procedural pain with sucrose in preterm neonates: is it effective and safe for repeated use over time?. The Clinical Journal of Pain 2005;21:543‐8. - PubMed
Storm 2002 {published data only}
    1. Storm H, Fremming A. Food intake and oral sucrose in preterms prior to heel prick. Acta Paediatrica 2002;91:555‐60. - PubMed
Suhrabi 2014 {published data only}
    1. Suhrabi Z, Taghinejad H, Valian K, Sayehmiri K, Taheri S. A comparative study on the efficacy of glucose and sucrose on the vaccination pain: a randomized controlled clinical trial. Journal of Clinical and Diagnostic Research 2014;8(10):PC01‐03. [PUBMED: 25478418] - PMC - PubMed
Taddio 2008 {published data only}
    1. Taddio A, Shah V, Hancock R, Smith RW, Stephens D, Atenafu E, et al. Effectiveness of sucrose analgesia in newborns undergoing painful medical procedures. Canadian Medical Association Journal 2008;179:37‐43. - PMC - PubMed
Taddio 2011 {published data only}
    1. Taddio A, Shah V, Stephens D, Parvez E, Hogan ME, Kikuta A, et al. Effect of liposomal lidocaine and sucrose alone and in combination for venipuncture pain in newborns. Pediatrics 2011;127:e940‐7. - PubMed
Thakkar 2016 {published data only}
    1. Thakkar P, Arora K, Goyal K, Das RR, Javadekar B, Aiyer S, et al. To evaluate and compare the efficacy of combined sucrose and non‐nutritive sucking for analgesia in newborns undergoing minor painful procedure: a randomized controlled trial. Journal of Perinatology 2016;36(1):67‐70. [PUBMED: 26583940] - PubMed
Tutag Lehr 2015 {published data only}
    1. Tutag Lehr V, Cortez J, Grever W, Cepeda E, Thomas R, Aranda JV. Randomized placebo controlled trial of sucrose analgesia on neonatal skin blood flow and pain response during heel lance. The Clinical Journal of Pain 2015;31(5):451‐8. [PUBMED: 24918475] - PubMed
Unceta‐Barranechea 2008 {published data only}
    1. Unceta‐Barrenechea A, Saitua Iturriaga G, Sainz de Rozas Aparicio I, Riveira Fernández D. Analgesia when taking heel lance blood in the newborn [Analgesia en la toma sanguínea de talónen los recién nacidos]. Anales de Pediatria (Barcelona) 2008;69:544‐7. - PubMed
Yilmaz 2010 {published data only}
    1. Yilmaz F, Arikan D. The effects of various interventions to newborns on pain and duration of crying. Journal of Clinical Nursing 2010;20(7‐8):1008–17. [PUBMED: 21054600] - PubMed

References to studies excluded from this review

Abad 1993 {published data only}
    1. Abad F, Diaz NM, Domenech E, Robayna M, Rico J, Arrecivita A, et al. Attenuation of pain related behavior in neonates given oral sweet solutions. 7th World Congress on Pain. Paris, 1993.
Abad 2001 {published data only}
    1. Abad F, Diaz‐Gomez NM, Domenech E, Gonzalez D, Robayna M, Feria M. Oral sucrose compares favourably with lidocaine‐prilocaine cream for pain relief during venepuncture in neonates. Acta Paediatrica 2001;90:160‐5. - PubMed
Ahuja 2000 {published data only}
    1. Ahuja VK, Daga SR, Gosavi DV, Date AM. Non‐sucrose sweetener for pain relief in sick newborns. Indian Journal of Pediatrics 2000;67:487‐9. - PubMed
Akman 2002 {published data only}
    1. Akman I, Özek E, Bilgen H, Ozdogan T, Cebeci D. Sweet solutions and pacifiers for pain relief in newborn infants. Journal of Pain 2002;3(3):199‐202. [PUBMED: 14622773] - PubMed
Aziznejad 2013 {published data only}
    1. Aziznejad P, Zahed Pasha Y, Ahmadpour Kacho M, Haji Ahmadi M, Mohammadzadeh I, Arzani A, et al. Comparing the effect of oral sucrose, breast milk and EMLA cream on acute pain during venipuncture in full term neonates. Journal of Babol University of Medical Sciences 2013;15(3):16‐23.
Barbier 1994 {published data only}
    1. Barbier P, Lionnet C, Jonville AP, Hamon B, Autret E, Laugier J, et al. Does the placebo effect exist in newborn infants?. Therapie 1994;49:113‐6. - PubMed
Barr 1993 {published data only}
    1. Barr RG, Oberlander T, Quek V, Brian J, Cassidy K‐L, Beauparlant J, et al. Dose‐response analgesic effect of intraoral sucrose in newborns [abstract]. Proceedings of the Society for Research in Child Development. 1993.
Barr 1995 {published data only}
    1. Barr RG, Young SN, Wright JH, Cassidy KL, Hendricks L, Bedad Y, et al. "Sucrose analgesia" and diphtheria‐tetanus‐pertussis immunizations at 2 and 4 months. Journal of Developmental Behavioral Pediatrics 1995;16:220‐5. - PubMed
Bilgen 2001 {published data only}
    1. Bilgen H, Ozek E, Cebeci D, Ors R. Comparison of sucrose, expressed breast milk, and breast‐feeding on the neonatal response to heel prick. Journal of Pain 2001;2:301‐5. - PubMed
Blass 1991 {published data only}
    1. Blass EM, Hoffmeyer LB. Sucrose as an analgesic for newborn infants. Pediatrics 1991;87:215‐8. - PubMed
Blass 1995 {published data only}
    1. Blass EM, Shah A. Pain‐reducing properties of sucrose in human newborns. Chemical Senses 1995;20:29‐35. - PubMed
Blass 2001 {published data only}
    1. Blass EM, Miller EW. Effects of colostrum in newborn humans. Dissociation between analgesic and cardiac effects. Journal of Developmental and Behavioral Pediatrics 2001;22:385‐90. - PubMed
Bucher 2000 {published data only}
    1. Bucher HU, Baumgartner R, Bucher N, Seiler M, Fauchere JC. Artificial sweetener reduces nociceptive reaction in newborn infants. Early Human Development 2000;59:56‐60. - PubMed
Curtis 2007 {published data only}
    1. Curtis SJ, Jou H, Ali S, Vandermeer B, Klassen T. A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department. BMC Pediatrics 2007;7:27. - PMC - PubMed
Dilli 2009 {published data only}
    1. Dilli D, Küçük IG, Dallar Y. Interventions to reduce pain during vaccination in infancy. Journal of Pediatrics 2009;154:385‐90. - PubMed
Efe 2007 {published data only}
    1. Efe E, Savaser S. The effect of two different methods used during peripheral venous blood collection on pain reduction in neonates. Journal of the Turkish Society of Algology 2007;19:49‐56. - PubMed
Fernandez 2003 {published data only}
    1. Fernandez M, Blass EM, Hernandez‐Reif M, Field T, Diego M, Sanders C, et al. Sucrose attenuates a negative electroencephalographic response to an aversive stimulus for newborns. Journal of Developmental and Behavioral Pediatrics 2003;24:261‐6. - PubMed
Gibbins 2000 {published data only}
    1. Gibbins S, Stevens B, Ohlsson A, Hodnett E, Pinelli J. Safety and efficacy of sucrose for procedural pain in neonates. The 5th International Symposium on Paediatric Pain. London, 2000:P98.
Gormally 1996 {published data only}
    1. Gormally SM, Barr RG, Young SN, Alhawaf R, Wersheim L. Combined sucrose and carrying reduces newborn pain response more than sucrose or carrying alone. Archives of Pediatrics and Adolescent Medicine 1996;150:47.
Graillon 1997 {published data only}
    1. Graillon A, Barr RG, Young SN, Wright JH, Hendricks LA. Differential response to intraoral sucrose, quinine and corn oil in crying human newborns. Physiology and Behavior 1997;62:317‐25. - PubMed
Harrison 2011 {published data only}
    1. Harrison D, Loughnan P, Manias E, Smith K, Johnston L. Effect of concomitant opioid analgesics and oral sucrose during heel lancing. Early Human Development 2011;87:147–9. - PubMed
Isik 2000b {published data only}
    1. Isik U, Ozek E, Bilgen H, Ors R, Cebeci D, Basaran M. Comparison of oral dextrose and sucrose solutions on pain response in neonates. Pediatric Research 2000;47:403A. - PubMed
Johnston 2000 {published data only}
    1. Johnston C. The efficacy of sucrose analgesia for procedural pain in preterm infants < 32 weeks in the first week of life [abstract]. Pediatric Research 2000;47:405A.
Joung 2010 {published data only}
    1. Joung KH, Cho SC. The effect of sucrose on infants during a painful procedure. Korean Journal of Pediatrics 2010;53:790‐4. - PMC - PubMed
Lewindon 1998 {published data only}
    1. Lewindon PJ, Harkness L, Lewindon N. Randomized controlled trial of sucrose by mouth for the relief of infant crying after immunization. Archives of Disease in Childhood 1998;78:453‐5. - PMC - PubMed
Mandel 2012 {published data only}
    1. Mandel R, Ali N, Chen J, Galic IJ, Levesque L. Nitrous oxide analgesia during retinopathy screening: a randomised controlled trial. Archives of Disease in Childhood. Fetal Neonatal Edition 2012;97:F83‐87. - PubMed
Mellah 1999 {published data only}
    1. Mellah D, Gourrier E, Merbouche S, Mouchino G, Crumiere C, Leraillez J. Analgesia with saccharose during heel capillary prick. A randomized study in 37 newborns of over 33 weeks of amenorrhea [Analgesie au saccharose lors des prelevements capillaires au talon. Etude randomisee chez 37 nouveau‐nes de plus de 33 semaines d'amenorrhee]. Archives of Pediatrics 1999;6:610‐6. - PubMed
Mohan 1998 {published data only}
    1. Mohan CG, Risucci DA, Casimir M, Gulrajani‐LaCorte M. Comparison of analgesics in ameliorating the pain of circumcision. Journal of Perinatology 1998;18:13‐9. - PubMed
Ozdogan 2010 {published data only}
    1. Ozdogan T, Akman I, Cebeci D, Bilgen H, Ozek E. Comparison of two doses of breast milk and sucrose during neonatal heel prick. Pediatrics International 2010;52:175‐9. - PubMed
Ramenghi 2002 {published data only}
    1. Ramenghi LA, Webb AV, Shevlin PM, Green M, Evans DJ, Levene MI. Intra‐oral administration of sweet‐tasting substances and infants' crying response to immunization: a randomized, placebo‐controlled trial. Biology of the Neonate 2002;81:163‐9. - PubMed
Razmus 2004 {published data only}
    1. Razmus IS, Dalton ME, Wilson D. Pain management for newborn circumcision. Pediatric Nursing 2004;30:414‐7. - PubMed
Reis 2003 {published data only}
    1. Reis EC, Roth EK, Syphan JL, Tarbell SE, Holubkov R. Effective pain reduction for multiple immunization injections in young infants. Archives of Pediatrics and Adolescent Medicine 2003;157:1115‐20. - PubMed
Sahebihag 2011 {published data only}
    1. Sahebihag MH, Hosseinzadeh M, Mohammadpourasl A, Kosha A. The effect of breastfeeding, oral sucrose and combination of oral sucrose and breastfeeding in infant's pain relief during the vaccination. Iranian Journal of Nursing and Midwifery Research 2011;16:9–15.
Scaramuzzo 2013 {published data only}
    1. Scaramuzzo RT, Faraoni M, Polica E, Pagani V, Vagli E, Boldrini A. Skin conductance variations compared to ABC scale for pain evaluation in newborns. Journal of Maternal‐fetal & Neonatal Medicine 2013;26(14):1399–403. [PUBMED: 23566033] - PubMed
Skogsdal 1997 {published data only}
    1. Skogsdal Y, Eriksson M, Schollin J. Analgesia in newborns given oral glucose. Acta Paediatrica 1997;86:217‐20. - PubMed
Stevens 1997b {published data only}
    1. Stevens B, Johnston C, Franck L, Petryshen P, Jack A, Narciso J, et al. Nonpharmacologic interventions for decreasing procedural pain in preterm neonates. Fourth International Symposium on Pediatric Pain. Helsinki, 1997:154.
Stevens 2000 {published data only}
    1. Stevens B, Petryshen P, Johnston C, Franck L, Jack A. The influence of consistent pain management on neonatal outcomes: preliminary findings. The 5th International Symposium on Paediatric Pain. London, UK, 2000:P96.
Taddio 2000 {published data only}
    1. Taddio A, Pollock N, Gilbert‐MacLeod C, Ohlsson K, Koren G. Combined analgesia and local anesthetic to minimize pain during circumcision. Archives of Pediatrics and Adolescent Medicine 2000;154:620‐3. - PubMed
Taddio 2003 {published data only}
    1. Taddio A, Shah V, Shah P, Katz J. Beta‐endorphin concentration after administration of sucrose in preterm infants. Archives of Pediatrics and Adolescent Medicine 2003;157:1071‐4. - PubMed
Taddio 2009b {published data only}
    1. Taddio A, Shah V, Katz J. Reduced infant response to a routine care procedure after sucrose analgesia. Pediatrics 2009;123:e425‐9. - PubMed
Vederhus 2006 {published data only}
    1. Vederhus BJ, Eide GE, Natvig G. Psychometric testing of a Norwegian version of the Premature Infant Pain Profile: an acute pain assessment tool. A clinical validation study. International Journal of Nursing Practice 2006;12:334‐44. - PubMed
Yoon 2001 {published data only}
    1. Yoon HB. Pain relieving effect of intraoral sucrose replacement in neonates. Korean Journal of Child Health 2001;7:35‐50.

References to studies awaiting assessment

Moradi 2012a {published data only}
    1. Moradi F, Imani A, Keyghobadi S, Nazari H, Ghorbani R, Keyghobadi T. Assessment of the effect of 20% oral sucrose on pain relief from Hepatitis B vaccine injection in full term infants. Journal of Zanjan University of Medical Sciences and Health Services 2012;20:79.
Moradi 2012b {published data only}
    1. Moradi F, Imani A, Keyghobadi S, Nazari H, Ghorbani R, Keyghobadi T, et al. Effects of intra‐oral intake of different concentrations of sucrose on biobehavioral pain response to immunizations in infants. Koomesh 2012;13(4):414‐9.
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References to ongoing studies

Campbell‐Yeo 2013 {published data only}
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ISRCTN59514984 {published data only}
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ISRCTN73259137 {published data only}
    1. ISRCTN73259137. Kangaroo mother care combined with sucrose to reduce pain responses in preterm infants. Controlled‐trials.com Identifier:, 2010.
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    1. Montanholi LL. Effect of skin‐to‐skin compared to sucrose for pain relief in infants undergoing repeated painful procedures: randomized clinical trial. www.ensaiosclinicos.gov.br/rg/RBR‐7nynr7/. RBR‐7nynr7, 2012.
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NCT01552993 {published data only}
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NCT01742520 {published data only}
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NCT01800318 {published data only}
    1. Hall RW. Does noninvasive electrical stimulation of acupuncture points (NESAP) reduce heel stick pain in infants?. ClinicalTrials.gov. Identifier: NCT01800318, 2011.
NCT01894659 {published data only}
    1. Angeles DM. Oral Sucrose Versus Glucose for Procedural Pain in Premature Neonates. ClinicalTrials.gov. NCT01894659 2013.
NCT01931020 {published data only}
    1. Datta V. Analgesic effect of oral 25% glucose versus oral 24% sucrose for pain relief during heel lance in preterm neonates. ClinicalTrials.gov. Identifier: NCT01931020, 2013.
NCT02133716 {published data only}
    1. Gómez LC. Efficacy of breast milk expressed and sucrose in procedural pain in preterm (LACTEET). ClinicalTrials.gov. Identifier: NCT02133716, 2013.
NCT02344368 {published data only}
    1. NCT02344368. The effect of sucrose on pain relief during venous blood sampling in preterm infants: a comparison of two different doses. ClinicalTrials.gov NCT02344368. ClinicalTrials.gov, 2015.
Passariello 2014 {published data only}
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Philip 2012 {published data only}
    1. Philip S. Effectiveness of human breast milk, table sugar vs sterile water for pain relief in premature infants undergoing a heel prick procedure in nursery of Christian Medical College and Hospital, Vellor. http://ctri.nic.in/Clinicaltrials/login.php. CTRI/2012/06/002730, 2012.
Roue 2013 {published data only}
    1. Roue J‐M. Prevention of the procedural pain in the newborn (ACTISUCROSE). ClinicalTrials.gov. NCT02109263, 2013.
Shah 2015 {published data only}
    1. Shah S. Comparing efficacy of music therapy, sucrose and combination of the two in neonates for pain relief during heel prick procedure. [Computer program]. Version ACTRN12615000271505. ANZCTR (Australian New Zealand Trials Registry), 2015.
Stevens 2014 {published data only}
    1. Stevens B. Sucrose practices for pain in neonates. NCT02134873. ClinicalTrials.gov 2014.

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