Double blind, randomized controlled trial

28 (29 - 36 weeks gestational age) infants, postnatal age 1-26 days

2 ml of 12% sucrose via syringe (n = 8) 2 minutes prior to venipuncture (n = 8).
2 ml of 24% sucrose via syringe (n = 8) 2 min prior to venipuncture (n = 8).
2 ml of spring water via syringe (n = 12) 2 min prior to venipuncture (n = 12).

Oxygen saturation, respiratory rate, heart rate (just before and just after administering the solution and 5 min after venipuncture), time spent in audible crying for three min following venipuncture.

One-way and two-way ANOVA used to evaluate outcomes
Data were reported as means and standard deviations for the three physiologic outcomes and as medians and interquartile ranges for cry duration. Data were collected at three time points; just before the administration of the solution, just after the solution and 5 minutes after venipuncture.
Adverse effects: were not evaluated

Double blind, randomized controlled cross-over trial

39 preterm neonates (mean 30.5 weeks gestational age), mean post natal age 27.2 days

2 ml of 25% (0.5 g) sucrose (n=39)
2 ml of water (n=39)
Via syringe over 2 minutes into infant's mouth

Rise in heart rate, 0₂ saturation, duration of first cry, total duration of crying, NFCS at the 3 phases of the venipuncture

Data were reported using means, standard deviations over the 3 phases of the venipuncture

Adverse effects: were evaluated.

Randomized controlled trial

285 infants between 2 weeks and 18 months old; 50 included in this review (only neonates at 2 weeks of age)

2 ml of 12% sucrose (n=16)

2 ml of sterile water (n=15)

No treatment (n=19)

Mean cry duration and percent time crying during and 3 minutes after subcutaneous injection

Data for percent time crying were presented in graphical form only. Data were requested and obtained directly from the author for this review.

Randomized controlled trial

72 newborn infants (postnatal age between 22 - 40 hours)

2 ml of 12% sucrose (n=8)
2 ml of protein solution (provimin) (n=8)
2 ml of lactose (n=8)
2 ml of dilute fat (coconut and soy oil blend) (n=8)
2 ml of concentrated fat (n=8)
2 ml of fat and lactose solution (n=8)
2 ml of Ross Special Formula (RSF) - artificial milk (n=8)
2 ml of Similac (n=8)

Solutions were given via syringe over a 2 min period

Crying time (percentage of procedure time spent crying; percentage of time spent crying during 3 min recovery period; number of infants that cried 20% or more during each recovery minute)

Sucrose vs. water, Similac vs. water and RSF vs water were compared using Mann-Whitney U statistic. Results were presented in graph form and means were reported in text.
Adverse events: were not evaluated

Randomized controlled trial

40 term newborn infants, 34 - 55 hours old

2 ml of 12% sucrose over two minutes via syringe (n=10)
2 ml of water via syringe over 2 minutes (n=10)
Pacifier dipped every 30 seconds in 12% sucrose solution for two minutes (n=10)
Pacifier dipped in water every 30 seconds for two minutes (n=10) prior to heel lance

Percentage of time spent crying 3 minutes after heel lance. Percentage of time spent grimacing, change in mean HR.

Data were reported in graph forms only
Results of ANOVA reported as p-values only (We have contacted the authors to obtain additional information).
Adverse effects: were not evaluated

Double-blind randomized controlled trial (repeated doses of sucrose)

105 preterm neonates (<31 weeks gestational age), postnatal age ≦ 48 hours

0.1 ml of sterile water up to 3 times for each painful procedure
0.1 ml of 24% sucrose up to 3 times for each painful procedure

Intervention was given prior to all painful procedures for a duration of 7 days

Pulse rate (over 1 day), Cortisol level (change in cortisol levels before/after procedure)

This paper assessed physiological stability over 1 full day of the 7 day study period.

Subset analyses were conducted. Results were reported as means and standard deviations.
Adverse events: were not evaluated

Randomized controlled trial

40 preterm infants <32 weeks GA

Sterile water group, mean GA=27 weeks, postnatal age mean= 45 days
Sucrose group, mean GA=29 weeks, postnatal age mean=43 days
Water + pacifier group, mean GA=30 weeks, postnatal age mean=41 days
Sucrose + pacifier group, mean GA=29 weeks, postnatal age mean=42 days

Two minutes before start of eye exam:
1 ml of sterile water (n=10)
1 ml of sucrose 33% (n=10)
1 ml of sterile water + pacifier (n=9)
1 ml sucrose 33% + pacifier (n=11)
*water or sucrose was given by mouth using a syringe

Premature Infant Pain Profile (PIPP) during eye examination

Data were presented in graph form and reported as means and standard deviations.
Results of ANOVA and independent t-tests reported as p-values

Adverse events: were not evaluated

Randomized, double blind, placebo controlled cross over trial

16 preterm infants (27 - 34 weeks gestational age), postnatal age approximately 42 days

2 ml of 50% sucrose via syringe into the mouth 2 minutes before heel lance
2 ml of distilled water via syringe into the mouth 2 minutes before heel lance
(n = 16, cross over design)

Increase in HR (bpm); Recovery time for HR (sec); recovery time for respirations (sec); crying (percent of total intervention); recovery time until crying stopped (sec); TcpO₂ (max increase -kPa); TcpO₂ (max decrease -kPa); TcpO₂ (difference between baseline and 10 minutes after end of intervention -kPa); TcpCO₂ (max decrease -kPa); TcpCO₂ (difference between baseline and 10 min after the end of intervention).

Results were presented in graph forms without mean values and standard deviations and/or in tables with medians with interquartile ranges. Wilcoxon signed rank test
Adverse effects: were not evaluated

Randomized controlled trial

150 term newborn infants, 3-4 days old

No treatment (n = 25)
2 ml of sterile water via syringe over 30 seconds (n = 25)
2 ml of 30% glucose via syringe (n = 25)
2 ml of 30% sucrose (n = 25)
Pacifier alone (n = 25) 2 minutes prior to venipuncture
2 ml of 30% sucrose via syringe followed by sucking a pacifier (n = 25)

Douleur Aigue du Nouveau-ne (DAN) scale

Mann-Whitney U test used to evaluate pain scores
Adverse effects: were evaluated

Randomized controlled trial

51 term infants, mean GA 39.3(1.2) in breastfeeding group; GA 39.4(1.1) in sucrose group

1 ml of 25% sucrose (n=50)

Breastfeeding (n=51)

PIPP during blood sampling, 2 min after heel lance

HR increase from baselines at 30 seconds following commencement of procedure

0₂ sat decrease

Duration of first cry, % crying time in first 2 minutes, and % in crying time during blood sampling

Randomized, double blind, placebo controlled, crossover study

23 preterm infants mean gestational age 26.4 weeks (range 24-29 weeks), postnatal ages 28-93 days

2 ml of sterile water via syringe (n=23)
2 ml of 24% sucrose via syringe (n=23)

Mydriatic eye drops (Phenylephrine HCl 1%, cyclopentolate HCl 0.2%) and local anaesthetic eye drops (proparacaine HCl 0.5%: 2 drops) were given to both groups prior to exam.

PIPP score at 5 min and 1 min pre-exam
PIPP score at eye speculum insertion
PIPP score 1 min and 5 min post-exam

Results were reported in means and standard deviations
Results of paired t-tests were reported as p-values

Adverse events: were evaluated-no adverse events experienced due to sucrose administration

Randomized double-blind controlled trial

33 preterm infants, median gestational age of 30 weeks

0.5 ml/kg of 25% sucrose before every minor painful procedure (venipuncture, arterial puncture, heel-lance, intravenous cannulation, endotracheal tube introduction, endotracheal tube suctioning, gavage insertion for feeding, removal of electrode leads and tape) (n=17)

0.5 ml/kg of sterile water (n=16)

Incidence of cry (% neonates crying)

Heart Rate (% neonates with HR greater than or equal to 160 bpm)

NFCS (% neonates with score greater than or equal to 3)

Activated Behavioural State (% neonates with score greater than or equal to 4)

Pain was assessed over a period of 4 days during morning blood collection (heel lance)

On day 1, no treatment was given to any neonate in order to collect baseline data. Solutions were administered to neonates before every painful procedure (listed above) on days 2 to 4.

The Mann-Whitney U Test was used to calculate the difference between sucrose and water groups for continuous variables. The X² Test was used to calculate the difference between sucrose and water groups for categorical variables.

No means or standard deviations reported.

Adverse events: were assessed

Randomized controlled trial

190 preterm and term infants, mean gestational age of 33.7 weeks, under 7 days postnatal age

0.5 ml of 24% sucrose via syringe to the anterior surface of the tongue followed by pacifier (n=64)
0.5 ml 24% sucrose without pacifier (n=62)
0.5 ml sterile water with pacifier (n=64)
2 minutes prior to heel lance

Premature Infant Pain Profile (PIPP) at 30 and 60 seconds after heel lance

One-way ANOVA to evaluate mean pain scores
Results were reported as means and standard deviations
Adverse effects: were evaluated

Randomized controlled trial, factorial design

94 normally developing newborns, mean gestational age 39.4 weeks on 2nd or 3rd day of life
Nine infants did not complete the study due to early discharge, nurse or testing room unavailability to obtain heel stick, infant removed from study prior to start date, technical difficulties.

No holding and sterile water given by pipette (n=21)
No holding and 0.25 ml of 24% sucrose solution (0.06 g) given by pipette (n=22)
Holding and sterile water given by pipette (n=20)
Holding and 0.25 ml of 24% sucrose solution (0.06 g) by pipette (n=22)
All solutions given 3 times at 30 second intervals

Percentage of time crying
Pain concatenation scores for facial activity
Mean heart rate
Mean vagal tone index
Measurements at pre intervention, 1, 2, and 3 minutes after heel lance

Factorial ANOVA to assess effects on behavioural and physiological measures
No means or standard deviations reported
Adverse effects: were not evaluated

Prospective randomized, blinded, placebo controlled study

32 preterm infants with birth weight less than 1.5 kg or gestational age under 28 weeks
Mean gestational age =28 wk +/- 1.6, mean postnatal age = 50.8 +/- 20.3 days

Sterile water (n=16)
24% sucrose (n=16)

Dose was adjusted by weight:

<1 kg = 0.5cm3 (0.12 g)
1 -1.5 kg = 1.0cm3 (0.24 g)
1.5 -2 kg = 1.5cm3 (0.36 g)
>2 kg = 2.0cm3 (0.48 g)

HR, RR and oxygen saturation at baseline, post-mydriatic, post-study drug, during eye exam, post eye exam
PIPP at  baseline, during eye exam, post eye exam
Crying time during eye exam
Blood pressure at baseline, post-mydriatics, during eye exam and post-eye exam

Results were reported as means and standard deviations.
Results of t-tests and ANOVAs were reported as p-values where a p-value of <0.05 was considered significant

Adverse events: were evaluated-choking, transient 0₂ desaturation

Randomized controlled trial

84 term newborns, approximately 17-19 hours old.

Sugar coated pacifier held in infant's mouth pre procedure to 3 minutes post procedure (n=21)
Water moistened pacifier (n=21)
2 ml of 12% sucrose via syringe into side of infant's mouth (n =21)
Routine care (n=21)

Salivary cortisol levels
Duration of cry
Vagal tone

Analysis using MANOVA to evaluate outcomes by groups
Results were presented in graph forms without mean values and standard deviations
Adverse effects: were not evaluated.

Randomized controlled trial

140 term (38-41 weeks gestational age)

Nothing (n=20)
Water (n = 20)
5% Glucose (n = 20)
33% Glucose (n = 20)
50% Glucose (n = 20)
33% Sucrose (n = 20)
50% Sucrose (n = 20)
via syringe into infant's mouth over 30 seconds

Heart rate before, during and 3 minutes after heel lance

ANOVA to evaluate heart rate across groups at each phase of the heel lance. Means and SD provided
Adverse effects: were evaluated

Randomized, double blind placebo controlled trial

60 term (37-42 weeks gestation) infants. 1 - 6 days of age.

2 ml of 12.5% sucrose 2 minutes prior to heel lance (n = 15)
2 ml of 25% sucrose 2 minutes prior to heel lance (n = 15)
2 ml of 50 % sucrose 2 minutes prior to heel lance (n = 15)
2 ml of sterile water 2 minutes prior to heel lance (n = 15)
All solutions were given by syringe on the tongue over less than one minute

Total time (seconds) crying over three minutes following heel lance
Time of first cry (seconds) following heel lance
Per cent change in heart rate after heel lance (at 1 min, 3 min and 5 min)

Analysis of non-parametric data was by the Mann-Whitney U test or a trend test. Total time crying in the first three minutes after heel lance was reported as medians and interquartile ranges. Changes in heart rate were expressed in means and standard deviations as a percentage of resting heart rate.
Adverse effects: were not evaluated

Randomized, blinded, controlled trial

Our sample was a subset of a larger study (n=128) that included older infants

Authors provided us with data for a subset of infants that fulfilled our inclusion criteria.

The subset included 99 hospitalised infants

Mean (SD) gestational age of placebo group=36.7 weeks (3.3)
Mean (SD) gestational age of treatment group=36.8 weeks (3.7)

1 ml of water 2 min prior to heel lance (n=46)
1 ml of 25% sucrose 2 min prior to heel lance (n=53)

*For infants weighing 1500g or less the does was reduced to 0.5 ml

NFCS at baseline, upon heel lance, during heel squeeze and completion of heel squeeze at 1 min, 2 min and 3 min of recovery

Duration of cry until 5 second pause, percentage of crying time during heel lance and squeeze, percentage of crying time during 3 min recovery period

Heart rate and O₂ saturation

Results were presented in graphs.
Results of Student's t-test, Pearson's Chi-squared test, Fisher's exact test and Mann-Whitney test were reported as p-values.

Adverse events: were not evaluated

Randomized controlled trial

119 full term male neonates undergoing circumcision, gestational age 38 weeks or more, postnatal age 12 hours or more

No treatment (n=40)
Dorsal Penile Nerve Block (DPNB) - 0.8 ml of 1% lidocaine (n=40)
Pacifier dipped in and packed with gauze soaked in 50% sucrose (n=39)

Heart rate and oxygen saturation (change from baseline and means for each interval of circumcision)

Results of change in heart rate and oxygen saturation for each group was reported as mean and SD. Mean heart rates for each interval of circumcision was graphed.

Mean heart rate and oxygen saturation were compared between groups using ANOVA. Characteristics of infants in the 3 groups were compared using X² test, Fisher exact test or ANOVA.

Adverse events: were not evaluated

Randomized controlled trial

113 healthy newborns gestational ages between 37 and 42 weeks, median post natal age= 2 days (range 2-5 days)

2 ml of 30% sucrose (n=28)
2 ml of 10% glucose (n=29)
2 ml of 30% glucose (n=28)
2 ml of distilled water (n=28)
syringed into the anterior third of the tongue for 1 minute
2 minutes prior to heel lance

Mean cry time during 3 minutes after heel lance
Mean maximum heart rate 3 minutes from heel lance
Mean recovery time for heart rate
Percent change in heart rate at 1, 2, 3 minutes after heel lance

One way ANOVA was used to evaluate mean cry time, recovery time and % change in heart rate
Results reported as means and standard errors of the mean
Adverse effects: were not evaluated

Randomized controlled trial

85 preterm infants (25 - 34 weeks gestational age) 2 - 10 days of age

0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance (n=27)
0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n=14)
0.05 ml of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n=24)
0.05 ml of sterile water via syringe into the mouth just prior to heel lance

Heart rate, oxygen saturation, behavioural facial actions, behavioural state
(NFCS) baseline and at three 30 second blocks

Data were analyzed using MANOVA (facial action). For heart rate repeated measures ANOVA was used with mean values but no standard deviations presented in graph form. For state repeated measures ANOVA was performed and no univariate means and standard deviations were presented.
02 saturation was dropped from analysis
Adverse effects: were not evaluated

Randomized controlled trial

48 preterm neonates mean gestational age of 31 weeks (range 25-34 weeks) within 10 days of birth

0.05 ml of 24% sucrose as a single dose, followed by 2 doses of sterile water (n=15)
3 doses of 0.05 ml of 24% sucrose (n=17)
3 doses of 0.05 ml of sterile water (n=16)
given by syringe to anterior surface of the tongue at:
2 minutes prior to heel lance
just prior to lancing
2 minutes after lancing

Premature Infant Pain Profile
(PIPP)
measured over five 30 second blocks of time

Repeated measures ANOVA was used to evaluate the effect of single versus repeated doses of sucrose.
Means and standard deviations for pain scores were obtained from the author
Adverse effects: were not evaluated

Randomized controlled trial

57 infants undergoing circumcision

Mogen method and water (n=15)
Mogen method and 24% sucrose (n=14)
Gomco method and 24% sucrose (n=14)
Gomco method and water (n=14)

Solutions were given via a dipped pacifier

Cry and grimacing during real time 10-second intervals.

Results were reported graphically. A 2-factor analysis of variance evaluated raw and percent duration of crying and grimacing. The Kolmogorov-Smirnov test for the equivalence of empiric distribution functions was used to evaluate differences in the distribution of cumulative crying and grimacing.

Adverse events: were not evaluated

Randomized study (blinded for cry but not for DAN)

104 term neonates older than 24 hours of life
Sucrose group mean postnatal age = 48 hours
Distilled water group mean postnatal age = 44 hours

2 ml of 20% sucrose (n=17)

2 ml of distilled water (n=15)

2 ml of Expressed Breast Milk (EBM) (n=18)

Non-nutritive sucking (NNS) (n=20)

Rocking (n=17)

Message (n=17)

DAN before heel prick and 30 sec, 1 min, 2 min and 4 min after heel prick.
Time of first cry in seconds (until baby took first inspiration after beginning of cry), total cry in seconds
Heart rate and SpO2 before heel prick, 2 min after heel prick and 4 min after heel prick

Results were graphed and reported as means and standard deviations (2 SD)
AvNOVA, Fischer's exact 't' test, multivariate analysis, Pearson's correlation test - some p-values were reported

Adverse events: were not evaluated

Randomized, double blind controlled trial

20 preterm infants, mean gestational age 30 weeks

Sucrose group: mean postnatal age = 23 days

Water group: mean postnatal age = 27 days

(0.5 - 2 ml)of 24% Sucrose (n=26)

(0.5 - 2 ml) of sterile water (n=25)

*Note: A total of 51 NG tube insertions were performed. Each baby was randomized to either the control or treatment group prior to each insertion. This was not a crossover study.

Incidence of cry

Heart Rate

Oxygen Saturation

NFCS (median)

Incidence of cry reported as percentage of neonates who cried. Heart rate and oxygen saturation measured as change (in bpm and % saturation, respectively) from baseline.

Adverse events were evaluated; brief apnea and self-limiting bradycardia reported in a few neonates, but not clinical intervention needed. No statistically significant differences between sucrose and control groups regarding incidence of adverse events.

Randomized, double blind, placebo controlled trial

30 preterm infants

Water group: mean gestational age = 27.3 weeks, mean postnatal age = 8.2 weeks

Sucrose group: mean gestational age = 26.5 weeks, mean postnatal age = 8.5 weeks

Water group: Pacifier and 3 doses of 0.1 ml sterile water drops (n=15)
Sucrose group: Pacifier and 3 doses of 0.1 ml 24% sucrose drops (n=15)

*Both groups received proparacaine hydrochloride 0.5% and were swaddled before the eye examination

PIPP at baseline, eye drops instillation, examination of left eye and 30 sec, 60 sec, 90 sec, and 120 sec after completion of the eye exam

Results were graphed and reported as means and standard errors of the means. A series of t tests were conducted and their p-values reported.

Adverse events: were not evaluated

Randomized, prospective study

33 preterm neonates, less than 33 weeks gestation

Mean (SD) gestational age at birth = 30 +/- 6 days

Mean (SD) gestational age at injection = 32 +/- 6 days

Non-nutritive pacifier

0.2 - 0.5 ml of 30% sucrose with pacifier

local application of EMLA with pacifier

0.2 - 0.5 ml of sucrose with EMLA and pacifier

DAN and NFCS scores

Heart rate, respiratory rate and oxygen saturation measured before, during and after injection

Fisher test, ANOVA of fixed effect and the Tukey method was used to compare groups.

Results were reported as means and standard deviations.

Adverse effects: were not reported

Randomized, double blind, placebo controlled trial

100 healthy, full term infants greater than or equal to 37 weeks gestation

1 ml of sterile water 2 min before heel lance (n=25)

1 ml of 50% sucrose 2 min before heel lance (n=25)

1 ml of sterile water 2 min before venipuncture (n=25)

1 ml of 50% sucrose 2 min before venipuncture (n=25)

NFCS score after skin puncture, during blood sampling and during compression to stop bleeding

Duration of first cry, ratio of crying to no crying, total procedure time

Intergroup comparisons were performed by the Kruskal-Wallis test Mann Whitney U test for continuous variables or by the X² test for categorical data

Results were reported as medians and ranges and means and standard deviations. P-values were also reported.

Adverse effects: were evaluated for the procedure itself, not sucrose

Randomized, blinded, crossover trial

31 preterm infants, mean (SD) gestational age 30.5 weeks (2.7), postnatal age of 20 days (16)

2 ml of sterile water
2 ml of 20% sucrose
2 ml of 20% glucose

All solutions were given 2 min before heel lance

Heart rate, respiratory rate, oxygen saturation and NFCS score at baseline, heel lance and 1 min, 2 min, 3 min, 4 min post heel lance.

Duration of first cry and total crying time

The differences in duration of crying time and blood collection were analyzed using the Friedman test.

Results were reported as means and standard deviations

Adverse effects: were not evaluated

Randomized controlled trial

102 healthy term infants, gestational age 37-42 weeks, median postnatal age 1.6 days (range1-15 days)

2 ml of 25% sucrose (n=35)
2 ml of human milk (n=33)
2 ml of sterile water (n=34)
syringed to anterior part of tongue for one minute
Heel prick done 2 minutes after intervention

Median crying time 3 minutes after heel lance
Percent change in heart rate 1, 2, 3 minutes after heel lance

Kruskal-Wallis 1-way ANOVA used to assess differences between groups
Medians and interquartile ranges reported for outcomes
Adverse effects: were not evaluated

Double-blind randomized controlled trial

100 newborn term infants [mean age 6 days (range 4-9)]

2 ml of 50% sucrose solution via syringe into the mouth over 30 seconds 2 minutes prior to heel lance
2 ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance

NIPS
Crying time (duration of first cry, crying time during heel lance, fraction of crying during sampling, crying time during first minute after end of sampling, total crying time)
NIPS one minute after heel lance and one minute after blood sampling
Change in heart rate at 0,1 minutes
Change in O₂ saturation at 0,1 minutes

Results were reported as medians and 5 and 95 percentiles
Statistical testing used Mann Whitney-U and Fisher's exact test
Adverse effects: were not evaluated

Randomized, double blind, placebo controlled crossover study

15 (32-34 weeks gestation) infants greater than 24 hours of age

1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel lance
1 ml of sterile water via syringe into mouth via syringe 2 minutes before heel lance.
(n=15, cross over design)

Duration of first cry (sec) following heel lance, percentage of time crying 5 minutes after heel lance, heart rate (at -2, 0, 1, 3, 5 min from heel lance), Behavioral scores (four facial expressions and the presence of cry (at -2, 0, 1, 3, 5 min from heel lance)

Medians and ranges were reported for duration of first cry, percent cry over 5 minutes and heart rate. For composite behavioural outcome scores data were presented in graph form only with no indication if data represent medians or means. Wilcoxon matched pairs signed rank test used to evaluate outcomes
Adverse effects: were evaluated

Randomized, single blind, placebo controlled trial

60 (37 - 42 weeks gestational age) 2 - 5 days old infants

2 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel lance (n = 15).
2 ml of 50% sucrose via syringe into mouth 2 minutes prior to heel lance (n =15).
2 ml of commercial sweet tasting solution (Calpol) via syringe into mouth 2 minutes prior to heel lance (n = 15).
2 ml of sterile water via syringe into mouth 2 minutes prior to heel lance (n = 15).

Duration of first cry (sec) following heel lance, percent time crying over 3 minutes following heel lance, percent change in heart rate over 5 min (-2, 0, 1, 3, 5 min from heel lance), behavioral scores (four facial expressions and the presence of cry (-2, 0, 1, 3, 5 min after heel lance)

Results were presented as medians and interquartile ranges for the pain score. For cry duration and percent crying over three minutes the data were presented as medians and inter quartile ranges. Percent change in heart rate was reported in graph form without indicating if data represent means or medians with standard deviations or errors. Mann-Whitney U test used to evaluate outcomes
Adverse effects: were not evaluated

Randomized double blind placebo controlled cross over trial

30 preterm infants (GA 32 - 36 weeks, postnatal age < 24 hours)

25% sucrose solution (volume not reported) was given via syringe into the mouth or via NG tube 2 minutes prior to first heel lance (n = 15), and via the alternate route for the second heel lance within 48 hours
Sterile water via syringe into the mouth or via NG-tube 2 minutes prior to first heel lance and for the second heel lance the alternate route within 48 hours
(cross over design, n= 30)

Percentage cry over 5 minutes after sampling;
Behavioral scores (four facial expressions and the presence of cry) at 1, 3, and 5 minutes after the lance for a total behavioural score

Mann Whitney-U and Wilcoxon matched pairs signed ranked test used to evaluate outcomes
Results reported as median and interquartile and total range
Adverse effects: were not evaluated

Randomized double blind trial

80 infants </= 90 days old, born at least 34 weeks' gestational age

Separated into 3 age groups: 1) 1-30 days, 2) 31-60 days, 3) 61-90 days

2 ml of sterile water via syringe 2 min before bladder catheterization (n=40)

2 ml of 24% sucrose via syringe 2 min before bladder catheterization (n=40)

Douleur Aigue du Nouveau-ne (DAN) scale;

Precentage of cry;

Time to return to behavioral baseline

Post hoc subgroup analyses, t-tests, chi-square tests, Mann-Whitney test, ANOVA and Breslow-Day (BD) test for homogeneity used to evaluate outcomes.

Results were reported as means and standard deviations. P-values were also reported.

Adverse events: were evaluated-no adverse effects experienced

Prospective randomized controlled trial

30 infants less than 32 weeks GA or weighing less than 1500 g

Control group mean gestational age of 28.8wk (range 25-31 wk)

Treatment group mean gestational age of 29.57wk (range 26-32 wk)

Control: No swaddling, no sucrose and not held by nurse

Treatment: Swaddled in a warm blanket, pacifier packed with gauze soaked in 24% sucrose and held by a nurse until 15 min after the eye exam

*All infants received eye drop instillation of 0.5% proparacaine and 1% tropicamide,  then 15 minutes later eye drop instillation of 0.5% tropicamide, 2.5% phenylephrin and, 0.5% tropicamide. Eye drops were all instilled into both eyes before the ROP exam.

Pulse rate, respiratory rate and oxygen saturation at baseline (30 min before instillation of proparacaine), 5 minutes before eye exam, 3 different times during eye exam and 5 minutes after the completion of the exam

Total crying time

Time required to return to baseline value

ANOVA and Wilcoxon signed rank test and the Pearson test were used to evaluate outcomes.

Results were reported as medians, means and standard errors of the means (SEM). p-values were also reported.

Adverse events: were not evaluated

Randomized, double blind, placebo controlled study

52 infants (37 - 42 weeks gestational age) 2-7 days of age

2 ml of 7.5% sucrose administered by a dropper into the mouth over a one minute period prior to heel lance (n = 26)
2 ml of sterile water administered by dropper into the mouth over a one minute period prior to heel lance (n = 26)

Percentage time crying during sampling and 3 minutes following the completion of the heel lance recorded on a standard audio tape recorder and analyzed blindly at a later date

Results are presented as medians only with no ranges
Mann Whitney-U test to evaluate duration of cry
Adverse effects: were not evaluated

Prospective, randomized, double-blind, placebo controlled trial

80 healthy term male newborns, 39.5 weeks mean gestation age, mean postnatal age 31.5 hours

Dorsal Penile Nerve Block (DPNB) with non buffered lidocaine (0.8 ml Lidocaine, 0.2 ml Saline), new padded restraint chair and pacifier dipped in water (n=20)

Dorsal Penile Nerve Block (DPNB) with buffered lidocaine (0.8 ml Lidocaine, 0.2 ml Sodium bicarbonate), rigid plastic restraint chair and pacifier dipped in water (n=20)

Dorsal Penile Nerve Block (DPNB) with non buffered lidocaine (0.8 ml Lidocaine, 0.2 ml Saline), rigid plastic restraint chair and pacifier dipped in 24% sucrose (n=20)

Dorsal Penile Nerve Block (DPNB) with non buffered lidocaine (0.8 ml Lidocaine, 0.2 ml Saline), rigid plastic restraint chair and pacifier dipped in water (n=20)

Behavioural Distress Scale (BDS) (scores at preinjection, at injection for DPNB, 2 min post injection, 4 min post injection and at circumcision)

Plasma cortisol level (30 min after start of circumcision)

Percentage of sleep during circumcision

Results were reported as mean and SD
ANOVA with repeated measures were used to compare distress scores. One way ANOVAs were used to examine plasma cortisol and sleep data.

Adverse effects: were not evaluated

Randomized, crossover, controlled trial

122 neonates, 27 - 31 weeks gestational age, less than 28 days of age
Johnston, 1999b
Subsample of 25 preterm neonates, 27-31 weeks gestational age, less than 28 days of age (refer to Stevens, 1999)

Prone positioning 30 minutes prior to heel lance. Pacifier dipped in sterile water and placed into the mouth 2 minutes prior to heel lance
Pacifier dipped in 24% sucrose and placed into the mouth 2 minutes prior to heel lance
No treatment. (n = 122, crossover design)

Premature Infant Pain Profile
(PIPP)

Repeated measures ANOVA and ANCOVA used to evaluate efficacy of treatment interventions
Means and standard deviations provided for pain scores
Adverse effects: were evaluated

Prospective, randomized, controlled trial

66 preterm infants, 26-30 weeks gestational age, <72 hours postnatal age

Control - no intervention (n=22)
0.1 ml of sterile water via syringe and pacifier (n=21)
0.1 ml of 24% sucrose via syringe and pacifier (n=23)

Solutions were given 2 min before every procedure during the first 28 days of life.

Premature Infant Pain Profile (PIPP)
Neonatal clinical outcomes and Neurobiological risk scores (NRBS)

Actual PIPP scores (mean, SD) were not reported. PIPP scores were analyzed by RMANOVA. Chi-squared analyses were used to compare the incidence of immediate and long-term adverse events.

Adverse events: were evaluated-adverse events were "low" and all immediate adverse events resolved spontaneously.

Randomized, controlled trial

48 preterm, median gestational age 32 wk, median postnatal age 14 days

2 ml of 15% sucrose, n = 12
1 ml of 25% sucrose, n =12
milk via NG tube, n= 12
milk via NG tube, + 25% sucrose, n = 12
All infants were given water prior to a second heel lance
Oral solutions were administered via syringe into infant's mouth 2 minutes prior to heel lance.
Milk was given during the last hour prior to heel lance.

Changes from before heel lance to during heel lance for:
Crying time
Changes in behavioural state
Skin conductance
Heart rate

Paired non-parametric tests (Wilcoxon test) used to compare the infant's intervention and control session
No median or IQR reported for each outcome
Adverse effects: were not evaluated.

Double-blinded, randomized controlled trial

240 newborns, mean gestational age 38.7 - 39.9 weeks, mean postnatal age 0.5 - 0.8 hrs

2 ml of 24% sucrose given to newborns of nondiabetic mothers, n = 60

2 ml of sterile water given to newborns of nondiabetic mothers, n = 60

2 ml of 24% sucrose given to newborns of diabetic mothers, n = 60

2 ml of sterile water given to newborns of diabetic mothers, n = 60

Solutions were given before all intramuscular injections, venipunctures and heel lances during the first 2 days of birth

PIPP score during procedure

Student t-test used to compare average PIPP scores between groups. Post-hoc analyses was performed after adjusting for baseline characteristics by use of a general linear model for intramuscular injection and venipuncture and linear mixed-model analysis for heel lances. Adverse events were analyzed using the X² test or the Student t-test

Adverse effects: were reported-no significant differences between groups in the incidence of adverse events which included spitting up, and blood glucose levels.

Prospective randomized controlled trial

150 term infants

Control - Facilitated tucking

NNS with water

2 ml 24% sucrose with NNS

Modified NFCS, mean crying time

Paper translated from Spanish to English

Abstract

Although this is a randomized controlled trial, four newborns were included twice (i.e. there were 55 events recorded for 51 participants), therefore, it was not possible to separate data for 51 newborns.

This is a non-randomized study. A single cohort was studied. The intervention was a non-sucrose sweetener.

Study did not include the use of sucrose.

Although a randomized controlled trial, the authors do not provide information on the number of infants in each group. Results are presented in graph form without indicating whether means or medians were used. No standard deviations are presented.

Excluded based on Post Natal Age (PNA) (2 and 4 months PNA).

This manuscript was published previously in the European Journal of Pediatrics ("Comparison of sucrose and human milk on pain response in newborns" by Ors et al, Eur J Pediatr, 158:63-66, 1999) and therefore, this article has been retracted by the Journal of Pain.
The editor of the Journal of Pain states that "Anyone citing this article must cite from the European Journal of Pediatrics and not from the Journal of Pain".

Although this is a randomized controlled trial the number of neonates in each group is not stated.

This is a controlled trial without randomization. The number of patients in each group is not stated.

Study not fully randomized.

This study used an artificial sweetener, glycine or breast milk as the intervention.

PNA 0-6 months.

Study not fully randomized.

Study not related to a painful procedure.

Abstract

Abstract

A randomized controlled crossover study. 60 crying infants were randomized to receive 250 ul of 24% sucrose solution, 0.25% quinine hydrochloride solution, or corn oil as well as water in a mixed parallel crossover design. Relative to water, sucrose persistently reduced crying, and transiently increased mouthing and hand-mouth contact. No painful stimulus was applied to the neonates.

Abstract

Abstract

Pain intensity not measured.

The infants in this study were older than the inclusion criteria for this review (mean age 17.1 weeks).

Randomized double blind cross-over study. Data analyzed by paired t-test. Results from the first exposure to sucrose or placebo could not be isolated.

Control group was not randomized.

Immunizations performed at 2, 3 or 4 months.

Study not fully randomized.

PNA (Mean PNA =9.5 weeks).

This study used glucose and breast milk as the interventions.

Abstract

Abstract

Not RCT and PNA included older infants.

Infants did not receive painful procedure.

Population subset of a larger study already included in the review.

Sucrose was not used as an intervention.

Not fully randomized.

Unknown

i) Blinding of randomization - Unclear
ii) Blinding of intervention -Unclear
iii) Complete follow-up - Unclear
iv) Blinding of outcome measurement -Unclear

138 neonates, 37 to 42 weeks postmenstrual age, greater than 24 hours postnatal age. Mean age of 2 days for all groups.

2 ml of 12.5% glucose plus pacifier

2 ml of 12.5% sucrose plus pacifier

2 ml of 12.5% glucose

2 ml of 12.5% sucrose

2 ml of sterile water

Crying behaviours, NFCS

Cry duration measured up to 3 minutes after heel lance in seconds.

Adverse effects: not reported

Unknown

Unknown

Unknown

Unknown

Unknown

72 infants, 22-40 hours old

Heel Lance

2 ml of either of the following solutions:

water       

12% sucrose    

protein mixture

7% lactose         

dilute fat (coconut and soy oil)    

concentrated fat                                 fat and lactose mixture  

Ross Special Formula (RSF) (water, protein, lactose, fat)           

milk

n= 8 for all groups

Crying time (%) during blood collection and 1, 2 and 3 minutes after heel lance   

Mean % of crying time per minute at 1, 2 and 3 minutes after heel lance (recovery period)

Mean proportions    

Graphically reported

Significantly less crying time during blood collection in the sucrose group (47%) compared to the water group (92%, p = 0.015).

40 term newborn infants, 34 - 55 hours old

Heel Lance

2 ml of 12% sucrose over 2 minutes via syringe (n=10)

2 ml of water via syringe over 2 minutes (n=10)

Pacifier dipped every 30 seconds in 12% sucrose solution for 2 minutes (n=10)

Pacifier dipped in water every 30 seconds for 2 minutes (n = 10) prior to heel lance

% time crying 3 minutes after heel lance

Mean change in HR

% time grimacing

Mean percentage

Mean change in beats per minute

Mean percentage

2 ml of 12% (0.24g) sucrose alone diminished cry duration from heel lance compared to water ( 8% vs. 50%, p = 0.003) and water with pacifier ( 8% vs. 35%, p = 0.002). Sucrose with pacifier (pacifier with 12% sucrose) more effective in reducing cry duration compared to water with pacifier (5% vs. 35%, p = 0.001) or water alone (50%, p = 0.002)

Mean heart rate increased significantly from treatment to heel lance in infants receiving water alone (mean increase of 17 beats per minute, p = 0.002) and water with pacifier (mean increase of 20 beats per minute, p = 0.005). Mean increase in heart rates also increased for the 2 ml of 12% (0.24g) sucrose and pacifier group (mean difference of 7.4 beats per minute, p = 0.05) but not for infants receiving 2 ml of 12% (0.24 g) sucrose alone (mean difference of 5.9 beats per minute, p = 0.142)

2 ml of 12%(0.24 g) sucrose reduced grimacing compared to water (p = 0.0003). 12% (0.24 g) sucrose with pacifier reduced grimacing compared to water (p = 0.001) and pacifier alone (p = 0.04).

16 preterm infants (27 - 34 weeks gestational age), postnatal age approximately 42 days

Heel Lance

2 ml of 50% sucrose via syringe into the mouth 2 minutes before heel lance.

2 ml of distilled water via syringe into the mouth 2 minutes before heel lance (n = 16, cross-over design

% time crying

Recovery time until crying stopped

Increase in HR

Recovery time for HR

TcpO₂ (max increase -kPa); TcpO₂ (max decrease -kPa); TcpO₂ (difference between baseline and 10 minutes after end of intervention -kPa); TcpCO₂ (max decrease -kPa); TcpCO₂ (difference between baseline and 10 min after the end of intervention), recovery time for respirations.

Not Reported

Median, IQR

Median, IQR

Cry duration (% of total duration of intervention) significantly reduced in 2 ml of 50% (1.0 g) sucrose group (71.5%) compared to control group (93.5%, p = 0.002)

Median increase in heart rate [beats per minute (bpm)] after heel lance were significantly reduced in the 2 ml of 50% (1.0 g) of sucrose group (35 bpm) compared to water (51 bpm), p = 0.005

No significant differences between groups with respect to measures for Tcp0₂ (p = 0.05) and TcpC0₂(p = 0.21)

101 term infants (39.3-39.4 weeks) gestational age

Heel Lance

Breastfeeding prior to heel lance (N=51)

1 ml 25% sucrose via syringe (N=50)

Duration of first cry, % crying time in first 2 minutes, and % crying time during blood sampling

HR increase from baselines at 30 seconds following commencement of procedure

0₂ sat decrease

PIPP during blood sampling, 2 min after heel lance.

Median, range

Median duration of first cry: BF group [3 (0 - 12)] compared to sucrose [21 (0-120)] p = 0.004

% crying during first 2 minutes:   BF group (4(0-100) compared to sucrose (45(0-100) p < 0.001

% crying during sampling: BF group (8 (0 -100) compared to sucrose (56.5 (0 -100) p = 0.0003

Median increase in HR from baseline to 30 sec after start of heel lance was significantly lower in breastfeeding group [13(-12 to 54)] compared to sucrose group [22(-32 to 65)], p =0.005

Median decrease in 0₂sat from baseline to 30 sec after start of heel lance was significantly greater in sucrose group [-3(-30 to 1)] compared to breastfeeding group [-1(-14 to 2)], p = 0.001

Median PIPP scores significantly lower in breastfeeding group (3.0) vs sucrose group (8.5), p < 0.0001

190 preterm and term infants , mean gestational age of 33.7 weeks, under 7 days post natal age

Heel Lance

0.5 ml of 24% sucrose via syringe to the anterior surface of the tongue followed by pacifier (n=64)
0.5 ml 24% sucrose without pacifier (n=62)
0.5 ml sterile water with pacifier (n=64)
2 minutes prior to heel lance

PIPP scores at 30 and 60 seconds after heel lance

Reported Means, SD

Statistically significant difference in mean PIPP scores at both 30 seconds (F = 8.23, p < 0.001) and 60 seconds (F = 8.49, p < 0.001) after heel lance in favour of 0.5 ml of 24% (0.12 g) sucrose group and 0.5 ml of 24%(0.12 g) sucrose with pacifier group. Post-hoc Tukey tests showed infants who received sucrose and pacifier had significantly lower PIPP scores after heel lance at 30 seconds (mean 8.16, SD 3.24) compared to infants receiving sucrose alone (mean 9.77, SD 3.04, p = 0.007) and water with pacifier (mean 10.19, SD 2.67, p < 0.001). At 60 seconds after heel lance, PIPP scores were significantly lower for 0.5 ml of 24% (0.12 g) sucrose with pacifier group (mean 8.78, SD 4.03) compared to the 0.5 ml of 24% (0.12g) sucrose alone group (mean 11.20, SD 3.25, p = 0.005) and water with pacifier group (mean 11.20, SD 3.47, p = 0.007). No significant differences in PIPP scores found between 0.5 ml of 24% (0.12 g) sucrose alone group or water with pacifier group at both follow-up times

94 term newborns, mean gestational age 39.4 weeks on 2nd or 3rd day of life

Heel Lance

No holding and sterile water given by pipette (n=21)

No holding and 0.250 ml of 24% sucrose solution given by pipette (n=22)

Holding and sterile water given by pipette (n=20)

Holding and 0.250 ml of 24% sucrose solution by pipette (n=22)

All solutions given 3 times at 30 second intervals

% time crying 1, 2, 3 minutes after heel lance

Mean HR preintervention, 1, 2, 3 minutes after heel lance, Mean vagal tone index preintervention, 1, 2, 3 minutes after heel lance

Pain concatenation scores for facial activity preintervention, 1, 2, 3 minutes after heel lance

Not reported

Crying decreased over time [F(2,80) = 10.0, p < 0.001] but no significant interaction noted for time with holding, taste, or holding and taste. Effect of taste on crying was significant [F(1,81) = 4.1, p < 0.05] in favour of 0.25 ml of 24% (0.18 g) sucrose. Effect of holding not statistically significant [F(1,81) = 3.0, p = 0.09)]. No statistically significant interaction between taste and holding to reduce crying [F(1,81) = 0.80, p = 0.37]. Effect of combined interventions was additive.

Although no significant differences in mean heart rate due to holding or sucrose as main effects, there was significant interaction between holding and taste [F(1,61) = 8.89, p< 0.004], indicating synergistic effect that was also dependent on preintervention heart rate [F(1,61) = 9.23, p < 0.004]. No significant main effects noted for vagal tone; as with heart rate, effect of vagal tone was dependent on preintervention vagal tone for both holding and taste interventions [F(1,60) = 4.82, p < 0.03]. Preintervention levels interacted to decrease heart rate and vagal tone in infants who had higher rates before interventions.

Pain concatenation scores measuring facial expressions of pain decreased over time [F(1,65) = 28.5, p <0.001]. Only the effect of holding reduced pain scores [F(1,65) = 5.6, p <0.02].No difference as to whether infant received sucrose (taste main effect F[1,65] 0.17,p =0.68

84 term newborns, approx. 17-19 hours old.

Heel Lance

Sugar coated pacifier (n=21)

water moistened pacifier (n=21)

2 ml of 12% sucrose (n =21)

routine care (n=21)

Duration of cry from procedure phase to 3 minutes post-procedure

Vagal tone and Vagal tone index

Salivary cortisol levels

Not reported

Significant decrease in duration of cry for the sugar-coated pacifier group compared to the control group (p = 0.001) and the water-pacifier group (p = 0.001).

Lower vagal tone during heel lance in the sugar coated pacifier group compared to the control group (p = 0.008) and oral sucrose group (p = 0.018). Lower vagal tone index in the sugar coated pacifier group compared to control group at heel lance (p = 0.019), and 6-10 minutes after (p = 0.007) and 11-15 minutes (p = 0.049) after heel lance.

No significant differences were found in salivary cortisol levels across groups (no p-value reported).

140 term (38-41 wk's gestational age)

Heel lance

Nothing (n=20) Water (n = 20) 5% Glucose (n = 20) 33% Glucose (n = 20 50% Glucose (n = 20) 33% Sucrose (n = 20) 50% Sucrose (n = 20)

Heart rate before, during and 3 minutes after heel lance

Mean, SD

No significant differences were found between groups for differences in heart rate at each of the 3 phases of the heel lance (p-value reported for 3 minutes after heel lance, p = 0.087; the difference between 3 minutes after heel lance and during heel lance, p = 0.068).

60 term (37-42 weeks gestation) infants. 1-6 days of age

Heel Lance

2 ml of 12.5% sucrose 2 minutes prior to heel lance (n = 15)

2 ml of 25% sucrose 2 minutes prior to heel lance (n = 15)

2 ml of 50 % sucrose 2 minutes prior to heel lance (n = 15)

2 ml of sterile water 2 minutes prior to heel lance (n = 15)

All solutions were given by syringe on the tongue over less than one minute

Total time crying over 3 minutes. Time of first cry after lance

Percent change in HR at 1, 3, 5 minutes after heel lance

Median, IQR

Reported Means and SEM

After heel lance, significant decreases in total crying time and duration of first cry in 2 ml of 50% (1.0 g) sucrose group compared with water (p = 0.02). Significant reduction in median time crying at end of first minute (p < 0.02) in 2 ml of 50% (1.0 g) sucrose group (35 sec; range 14 - 60) compared with water (60 sec; range 50 -60). In second minute, duration of cry was significantly less in 2 ml of 50% (1.0 g) sucrose group (0 sec; range 0 - 25) and in 2 ml of 25% (0.5 g) sucrose group (18 sec; range 0 - 55) compared to water (60 sec; range 40 - 60), p = 0.003, p = 0.02 respectively

Significant decrease in percent change in heart rate 3 minutes after heel lancing (p = 0.02) in the 2 ml of 50% (1.0 g) sucrose group (mean 0.1%, SE 3.3) compared to water group (mean 17.5%, SE 6.0)

99 sick hospitalized infants, mean (SD) gestation age 36.7 weeks (3.3) (treatment), 36.8 weeks (3.7) (control)  (author provided data on a subset of infants from a larger study (n=128) that fulfilled our inclusion criteria)

Heel Lance

1 ml of water (n=46)

1 ml of 25% sucrose (n=53)

For infants weighing 1500g or less, the dose was reduced to 0.5 ml

Duration of cry until 5 second pause, incidence and duration of crying time during the heel lance and squeeze and during the 3 minute recovery period

Heart rate (HR) at baseline, heel lance, during heel lance and 1, 2, 3 minutes post heel lance

Oxygen saturation at baseline, heel lance, during heel lance and 1, 2, 3 minutes post heel lance

Four point subset of the Neonatal Facial Coding System (NFCS) (brow bulge, eye squeeze, nasolabial furrow, stretch mouth) at heel lance, during heel lance and 1, 2, 3 minutes post heel lance

Mean, SD (collected from authors)

Mean length of first cry was higher in the water group [70.5 (83.6)] compared to the sucrose group [46.8 (63.1)]. The sucrose group cried 57.1% of the procedure time compared to 58.8% in the water group. The mean total duration of cry during the heel lance was 84.7 seconds (68.8) in the sucrose group and 87.4 seconds (87.1) in the water group.

The mean (SD) HR upon heel lance was 163.0 (17.9) bpm in the sucrose group and 159.5 (19.2) bpm in the water group. HR at 30 seconds from the beginning of the procedure was 175.4 (22.2) and 172.8 (23.6) bpm in the sucrose and water groups, respectively. The HR in both groups decreased after the procedure to 152.1 (22.5) bpm in the sucrose group and 154.2 (29.1) bpm in the water group 2 minutes post heel lance.

Results of SpO₂ were similar between the two groups.

Mean facial scores were significantly reduced at heel lance [2.74 (1.8)] in the sucrose group compared to the water group [ 2.94 (1.6) ; p = 0.02] and at 1 minute (p = 0.04) and 2 minutes (p = 0.046) post-heel lance. No significant differences occurred at 3 minutes post heel lance.

113 healthy term newborns gestational ages between 37 and 42 weeks, median post natal age= 2days (range 2-5 days)

Heel Lance

2 ml of 30% sucrose (n=28)

2 ml of 10% glucose (n=29)

2 ml of 30% glucose (n=28)

2 ml of distilled water (n=28)

syringed into the anterior third of the tongue for 1 minute 2 minutes prior to heel lance

Mean cry time during 3 minutes after lance

Mean maximum heart rate 3 minutes from heel lance

Mean recovery time for heart rate

% change in heart rate at 1, 2, 3 minutes after heel lance

Reported means, SD

Reported Means and SEM

Infants who received 2 ml of 30% (0.6 g) sucrose (mean crying time of 61 seconds) cried significantly less than those who received 30% glucose (mean crying time of 95 seconds), 10% glucose (mean crying time of 103 seconds) or sterile water (mean crying time of 105 seconds), p = 0.02

No significant difference between groups with respect to maximum heart rate after heel lance, (p = 0.71), or mean recovery time, (p = 0.09). No significant difference found in percent change in heart rate at 1 or 3 minutes after heel lance, (p = 0.14, p = 0.53), respectively. At 2 minutes after heel lance, percent change in heart rate favoured group receiving sucrose (p = 0.05) compared to other groups

85 preterm infants (25 - 34 weeks gestational age) 2 - 10 days of age

Heel Lance

0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance (n = 27)
0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 14)
0.05 ml of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 24)
0.05 ml of sterile water via syringe into the mouth just prior to heel lance

HR at baseline and 3 x 30 second blocks

Behavioural facial actions(Neonatal Facial Coding System-NFCS) at baseline and 3 x30 second blocks

Not reported

Although heart rate increased across all phases of procedure [F(3,59) = 2.94, p < 0.04], there was no significant differences noted between groups [F(3,59)=0.682, p = 0.566]

Decrease in percent facial action in 0.05 ml of 24% (0.012 g) sucrose alone group and combined 0.05 ml of 24% (0.012 g) sucrose and rocking group compared to water group, F (6, 150) = 2.765, p < 0.02

48 preterm neonates mean gestational age of 31 weeks (range 25-34 weeks) within 10 days of birth

Heel Lance

0.05 ml of 24% sucrose as a single dose, followed by 2 doses of sterile water (n=15)
3 doses of 0.05 ml of 24% sucrose (n=17)
3 doses of 0.05 ml of sterile water (n=16)
given by syringe to anterior surface of the tongue at:
2 minutes prior to heel lance
just prior to lancing
2 minutes after lancing

PIPP scores in five 30 second blocks

Reported Means, SD

Statistically significant difference between groups (F = 9.143, p < 0.0001) for mean PIPP scores. Post-hoc analysis found significantly lower PIPP scores with repeated doses of 0.05 ml of 24% (0.012 g) sucrose compared to placebo groups across all blocks of time, p < 0.05. PIPP scores for repeated doses of 0.05 ml of 24% (0.012 g) sucrose were significantly lower compared to single doses of 0.05 ml of 24% (0.012 g) sucrose (8.25 vs. 6.25) only at last block of time, p < 0.05. PIPP scores for single doses of 0.05 ml of 24% (0.012 g) sucrose compared to placebo showed trend towards statistical significance in favour of 0.05 ml of 24% (0.012 g) sucrose (F = 3.465, p = 0.07)

104 term neonates, postnatal age older than 24hr of life

Sucrose group mean postnatal age 48 hours

Distilled water groups mean postnatal age 44 hours

Heel lance

2 ml 20% sucrose instilled into mouth via a dropper (n=17)

2 ml distilled water instilled into mouth via a dropper (n=15)

rocking (n=17)

massage (n=17)

expressed breast milk (n=18)

non-nutritive sucking (n=18)

Time of first cry in seconds, Total cry in seconds

Heart rate before heel prick, 2 min after heel lance and 4 min after heel lance

Oxygen saturation before heel lance, 2 min after heel lance and 4 min after heel lance

Douleur Aigue du Nouveau-ne (DAN) scale before the heel lance and 30 seconds, 1 min, 2 min, 4 min after heel lance

Means, SD reported

Not reported

Mean, SD

No significant difference between sucrose group and any other group for time of first cry

NNS and rocking significantly reduced total duration of cry, p < 0.05

No significant difference in heart rate between the groups at any time point.

No significant difference in oxygen saturation between the groups at any time point.

Significantly reduced DAN scores at 30s after the heel lance for the sucrose group (mean 7.6, SD 14, p < 0.05)  however this was not sustained at 1,2 and 4 minutes 

NNS and rocking sigificantly decreased the DAN scores at 2 and 4 minutes post heel lance, p < 0.05.

31 healthy preterm newborns, mean gestational age 30.5 weeks, mean postmenstrual age 32.3 weeks

Heel Lance

2 ml of 20% sucrose

2 ml of 20% glucose

2 ml of water

Infants received all 3 interventions at different times

Duration of first cry and total crying time

Heart rate (HR) at baseline, during heel lance and 1, 2, 3, 4 and 5 minutes post heel lance

Oxygen saturation and respiratory rate at baseline, during heel lance and 1, 2, 3, 4 and 5 minutes after heel lance

Neonatal Facial Coding System (NFCS) scores during heel lance and 1, 2, 3, 4 and 5 minutes post heel lance

Mean, SD

Significantly increased duration of first cry and total crying time in the water group compared to the sucrose and glucose groups (p = 0.005 and p = 0.007, respectively). No significant differences in cry characteristics were observed between the sucrose and glucose groups.

Significantly higher HR in the water group (mean 175, SD 20.8) compared to the sucrose (mean 166, SD 17.6) and glucose groups (mean 165, SD 17.5) at 1 minute following heel lance (p= 0.007). No significant differences between the sucrose and glucose groups.

Significantly higher NFCS score in the placebo group in the fourth minute following heel lance (mean 1.3, SD) and fifth minute following heel lance (mean 1.0, SD 1.0) compared to the sucrose (mean 0.5, SD 1.7; mean 0.3, SD 1.3 respectively) and glucose groups (mean 0.2, SD 0.5; mean 0.1, SD 0.3 respectively) p= 0.009 at fourth minute and p = 0.049 at fifth minute. There were no significant differences between the sucrose and glucose groups.

102 healthy term infants, gestational age 37-42 weeks, median postnatal age 1.6 days (range1-15 days)

Heel Lance

2 ml of 25% sucrose (n=35)

2 ml of human milk (n=33)

2 ml of sterile water (n=34)

All solutions syringed onto anterior part of tongue for one minute

Heel prick performed 2 minutes after intervention

Median cry time during 3 minutes after lance

Percent change HR 1,2,3 minutes after heel lance

Median, IQR

Significant decrease in crying times for 2 ml of 25% (0.5 g) sucrose group (median 36, interquartile range 18-43) compared to human milk (median 62, interquartile range 29-107) and sterile water [(median 52, interquartile range 32-158), p = 0.0009]. Recovery time for crying was significantly reduced in 2 ml of 25% (0.5 g )sucrose group (median 72, interquartile range 48-116) compared to human milk (median 112, interquartile range 72-180) and sterile water [(median 124, interquartile range 82-180), p = 0.004]

Percent change in heart rate after heel lance was significantly lower in the group receiving 2 ml of 25% (0.5g) sucrose compared to groups receiving human milk and sterile water at 1, 2 and 3 minutes (p = 0.008, p = 0.01, p = 0.002, respectively)

100 newborn term infants [mean age 6 days (range 4-9)]

Heel Lance

2 ml of 50% sucrose solution via syringe into the mouth over 30 seconds 2 minutes prior to heel lance

2 ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance

Median crying time during heel lance, fraction of crying during sampling, crying time during first minute after end of sampling, total crying time

Change HR 0,1 minutes

Oxygen saturation at 0, 1 minutes

Neonatal Infant Pain Scale (NIPS) scores 1 minute after heel lance and 1 minute after blood sampling

Median, 5th and 95th percentiles

Median duration of first cry in group receiving 2 ml of 50% (1 g) sucrose was significantly lower (18 seconds (2-75) compared to placebo group [(22 seconds (11-143), p = 0.03]. Median crying time during heel lance in the sucrose group was lower (26 seconds (2-183) compared to placebo group [(40 seconds (12 - 157), p = 0.07]. Median fraction of crying during sampling in 2 ml of 50% (1 g) sucrose group was significantly lower (43% (4-100) compared to placebo group [(83% (20 - 100), p = 0.004]. Median crying time during first minute after end of sampling in 2 ml of 50% (1 g) sucrose group was significantly lower (3 seconds (0 - 58) compared to placebo group [(16 seconds (0-59), p = 0.004]. Median total time crying in 2 ml of 50% (1 g) sucrose group was significantly lower (30 seconds (2 - 217) compared to placebo group [(71 seconds (13-176), p = 0.007]

No significant HR differences between groups, p = 0.05

No significant differences between groups with respect to changes in oxygen saturation, p = 0.8

Median NIPS scores 1 minute after heel lance were lower in 2 ml of 50% (1.0 g) sucrose group compared to placebo group [(3(0-7), 6(0-7), respectively), p = 0.04]. Median NIPS scores 1 minute after end of blood sampling were lower in 2 ml of 50% (1.0 g) sucrose group [0 (0-7)] compared to placebo group [(2 (0-7), p = 0.05]

15 preterm (32-34 weeks gestation) infants greater than 24 hours of age

Heel Lance

1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel lance

1 ml of sterile water via syringe into mouth 2 minutes before heel lance (n=15, cross-over design)

Duration of first cry and % time crying 5 minutes after lance

Heart rate (at -2, 0, 1,3,5 minutes from heel lance)

Behavioral scores (four facial expressions and the presence of cry) -2,-1,0,1,2,3,5 minutes

Quality/intensity of sucking

Median, IQR

Not reported

Not reported

Significant decrease in total percentage of time crying over 5 minutes (median 6%, interquartile range 3.3 - 15.3) in the 1 ml of 25% (0.25 g) sucrose group compared with water group [(median 16.6%, range 5 - 27.3), p = 0.018]. Duration of first cry was significantly decreased in the 1 ml of 25% (0.25 g) sucrose group (median 12 sec, interquartile range 8 - 22 sec) compared to control group [(median quartile 23 sec, range 15 - 45), p = 0.004]

No significant differences in HR between groups, p-value not reported

Mean pain scores were significantly lower in the groups receiving 1 ml of 25% sucrose (0.25 g)of sucrose at both 1 minute and 3 minutes after heel lance ( p = 0.01, p = 0.03, respectively).

The clinical interpretation of the quality of sucking was significantly more intense in the 1 ml of 25% (0.25 g) sucrose group than in the water group (p = 0.04).

60 term (37 - 42 weeks gestational age) 2 - 5 days old infants

Heel Lance

2 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel lance (n = 15)

2 ml of 50% sucrose via syringe into mouth 2 minutes prior to heel lance (n =15)

2 ml of commercial sweet tasting solution (Calpol) via syringe into mouth 2 minutes prior to heel lance (n = 15)

2 ml of sterile water via syringe into mouth 2 minutes prior to heel lance (n = 15)

Duration of first cry after lance

% time crying over 3 minutes after heel lance

Percent change in heart rate over 5 minutes (at -2, 0, 1,3,5 minutes from heel lance)

Behavioral scores (four facial expressions and the presence of cry) -2,-1,0,1,2,3,5 minutes

Median, IQR

Not Reported

Median, IQR

Significant decrease in duration of first cry and percent crying during 3 minutes after heel lance in the 2 ml of 25% (0.5 g) sucrose, 2 ml of 50% (1.0 g) sucrose and Calpol groups (p = 0.02) (data in graph form only)

Significant increase in heart rate for 3 minutes after heel lance in water group compared with 2 ml of 50% (1.0 g) sucrose group and Calpol group, p = 0.009

Pain score (0 - 5) was significantly higher in water group (score = 2, range 1-5) than in other three groups: 2 ml of 50% (1 g) sucrose group (score = 0, range 0 - 3); 2 ml of 25% (0.5 g) sucrose group (score = 0, range 0 - 2); Calpol group (score = 0, range 0 -1), p = 0.05

30 preterm infants (GA 32-36 weeks, postnatal age < 24 hours)

Heel Lance

25 % sucrose solution (volume not reported) was given via syringe into the mouth or via NG tube 2 minutes prior to first heel lance (n = 15), and via the alternate route for the second heel lance within 48 hours

Sterile water via syringe into the mouth or via NG-tube 2 minutes prior to first heel lance and for the second heel lance the alternate route within 48 hours (cross over design, n= 30)

% cry over 5 minutes after sampling

Behavioral scores (four facial expressions and the presence of cry) at 1, 3, and 5 minutes after the lance for a total behavioral score

Median, IQR

Median percentage cry in intraoral water group was 22% (interquartile range 10.6 - 40) and 27% (interquartile range 11.6 - 47) for infants in NG-tube water group. Median percentage cry in intraoral 25% sucrose group was 6% (interquartile range 0.6 -15) and 18.3% (interquartile range 11.6 - 41.6) for NG-tube 25% sucrose group. Significant reduction in crying time (p = 0.006) noted in the 25% sucrose group compared with water group when infants received 25% sucrose intraorally, not via NG-tube route. For infants in 25% sucrose group, significant reduction in crying time noted (p = 0.008) when solution given intraorally compared to NG-tube route

Behavioral scores for the intraoral water group was 9 (interquartile range 6-12) and 10 (interquartile range 6-14) for N-G tube water group. Behavioural scores for intraoral 25% sucrose group was 5 (interquartile range 3-6) and 9 (interquartile range 8-10) for NG-tube sucrose group. Significant reduction in behavioral scores noted in 25% sucrose group (p = 0.002) compared with water group when infants received 25% sucrose intraorally but not via N-G route. For infants in 25% sucrose group, there was significant reduction in behavioral score, p = 0.001 when solution was given intraorally compared to via NG-tube

52 term infants (37 - 42 weeks gestational age) 2-7 days of age.

Heel Lance

2 ml of 7.5% sucrose administered by a dropper into the mouth over a one minute period prior to heel lance (n = 26).

2 ml of sterile water administered by dropper into the mouth over a one minute period prior to heel lance (n = 26).

% cry over 3 minutes after sampling

Median only

No significant differences in median percentage time crying between group receiving 2 ml of 7.5% (0.15 g) sucrose (74.3%) compared to group receiving water (73.2%). No significant differences between groups in duration of cry after 1 minute (p = 0.65), 2 minutes (p = 0.52) and 3 minutes (p = 0.72). No difference in time to cessation of crying (p = 0.16)

122 neonates, 27 - 31 weeks gestational age, less than 28 days of age

Heel Lance

Prone positioning 30 minutes prior to heel lance

Pacifier dipped in sterile water and placed into the mouth 2 minutes prior to heel lance

Pacifier dipped in 24% sucrose and placed into the mouth 2 minutes prior to heel lance

Control:Containment in SnuggleUp device (n = 122)

NB: All infants were contained in SnuggleUp device

PIPP scores at 30 and 60 seconds

Reported Means, SD

Main effect of treatment for mean PIPP scores, [F (16.20), p < 0.0001]. Post hoc analysis revealed significant reduction in PIPP scores 30 seconds after heel lance in sucrose group (pacifier dipped in 24 % sucrose - estimated at 0.02g), (mean 7.87, SD 3.35), compared to control group [(mean 9.80, SD 3.55), F (24.09), p < 0.0001]. Statistically significant reduction in PIPP scores in pacifier and water group (mean 8.44, SD 3.55) compared to control group [(mean 9.80, SD 3.55), F (9.00), [ p = 0.003]. Trend towards lower PIPP scores with sucrose and pacifier group compared to water and pacifier group [(F (3.62), p < 0.05)]

66 preterm infants (26-30 weeks), postnatal age 72 hours

Heel lance

Standard care-positioning and swaddling (n=21)

Standard care-positioning and swaddling  and 0.1 ml sterile water via syringe into the mouth immediately followed by a pacifier 2 min prior to painful procedure (n=23)

Standard care-positioning and swaddling  and 0.1 ml 24% sucrose via syringe into the mouth immediately followed by a pacifier 2 min prior to painful procedure (n=22)

These interventions were given every time there was a painful procedure during the first 28 days of life

PIPP at day 7, 14,21,28 at routine heel lance

Not reported

Significant main effect of group (p =0.03) with differences occurring between the sucrose+pacifier group and standard care group; t(60)= -2.54, p = 0.01). Mean PIPP scores were generally higher in the standard care group.

No significant main effect of time.

Adverse Effects: No group differences for adverse events, clinical outcomes or neurobiological risk status.

48 preterm, median gestational age of 32 wk, median postnatal age of 14 days

Heel Lance

2 ml of 15% sucrose, n = 12
1 ml of 25% sucrose, n =12
milk via NG tube n= 12
milk via NG tube, + 25% sucrose, n = 12
All infants were given water prior to a second heel lance

Differences in crying time for pre heel lance to heel lance procedure

Changes in heart rate from pre-heel lance to heel lance procedure

Difference in skin conductance from pre heel lance to heel lance procedure

Not reported

Significantly less crying in Infants receving 1 ml of 25% sucrose (p < 0.05) and food (milk) + 1 ml of 25% sucrose (p < 0.05).

No significant differences between groups in changes in heart rate from pre-heel lance to heel lance procedure (no p- value reported)

No statistically significant smaller increase in skin conductance variables compared to their water control session (p-value not reported).

150 term infants

Heel Lance

Facilitated tucking

NNS + water

NNS + 2 ml 24% sucrose

Mean crying time between groups

Modified NFCS

Mean, SD

Statistically significant differences in crying time between control group and 2 intervention groups (p < 0.001). No significant difference between sucking with placebo and sucking with sucrose groups (p = 0.735).

Statistically significant differences in pain score between control group and 2 intervention groups (p < 0.001). No significant difference between sucking with placebo and sucking with sucrose groups (p = 0.105).

28 preterm (29 - 36 weeks gestational age) infants, postnatal age 1-26 days

Venipuncture

2 ml of 12% sucrose via syringe (n = 8)

2 ml of 24% sucrose via syringe (n = 8)

2 ml of spring water via syringe (n = 12) 2 minutes prior to venipuncture

Time crying for 3 minutes after venipuncture

Heart rate:pre solution, post solution 5 minutes after venipuncture

Mean 02 saturation and respiratory rate pre solution, post solution, 5 minutes after venipuncture

Median, IQR

Mean,SEM

Mean, SD

Significant group effect noted, (F (2, 25) = 4.26; p = 0.0256) for cry duration 3 minutes after venipuncture. Cry duration was significantly reduced in 2 ml of 24% (0.48 g) sucrose group (19.1 sec) compared to 2 ml of 12% (0.24 g) sucrose (63.1 sec) and water (72.9 sec) groups (p < 0.05)

Significant group effect for HR, F (2, 25) = 6.37, p = 0.006. Overall time effect, F (2, 50) = 14.15, p < 0.001. No significant interaction between treatment group and time. Post hoc Tukey test showed that group receiving 2 ml of 12% sucrose (0.24 g) had lower HR compared to the 2 ml of 24% sucrose group (0.48 g) or water group at all three time points (pre solution, p = 0.048; post solution, p = 0.010; 5 minutes after, p = 0.007).

No significant differences noted between groups over time for oxygen saturation and respiratory rates (no p-values reported ).     

39 preterm neonates (mean 30.5 weeks gestational age), mean postnatal age 27.2 days

Venipuncture

2 ml of 25%(0.5g) sucrose administered by syringe into front of infant's mouth over 2 minutes, 4 minutes prior to venipuncture

Duration of first cry (beginning to end of first cry); total duration of crying (onset of first cry to cessation of all crying)

Mean change in heart rate from pre-procedure, procedure and post-procedure phase of venipuncture

Mean Sa02 (%) at pre-procedure, procedure and post-procedure

Neonatal Facial Coding System (NFCS) changes across 3 phases of venipuncture

Mean SD

Mean duration of first cry lower in infants who received sucrose [18.6 (24.4) seconds] compared to infants who received water [52.3 (56) seconds] (estimated treatment effect = 33.7, p < 0.001). Mean total duration of crying was significantly lower in infants who received sucrose [31.9(41.9) seconds] compared to infants who received water 7 [2.5(66.7) seconds] (estimated treatment effect = 40.6, p < 0.001).

Mean change in heart rate from pre procedure to procedure was lower in the infants receiving sucrose compared to water (estimated treatment effect = 7.5, p = 0.003). Mean change in heart rate from pre-procedure to post procedure was lower in the infants who received sucrose compared to water (estimated treatment effect = 4.16, p = 0.036).

No significant differences between groups with respect to changes in oxygen saturation from pre-procedure to procedure phase (p = 0.17)

Changes in mean NFCS scores were significantly lower in the sucrose group compared to water group from pre-procedure to procedure phase (estimated treatment effect = 1.08, p = 0.013) and between the pre-procedure and post-procedure phase (estimated treatment effect = 2.39, p < 0.001).

150 term newborn infants, 3-4 days old

Venipuncture

No treatment (n = 25)

2 ml of sterile water via syringe over 30 seconds (n = 25)

2 ml of 30% glucose via syringe (n = 25)

2 ml of 30% sucrose (n = 25)

Pacifier alone (n = 25) 2 minutes prior to venipuncture

2 ml of 30% sucrose via syringe followed by sucking a pacifier (n = 25)

Douleur Aigue du Nouveau-ne (DAN) scale

Median, IQR

Median pain scores with interquartile ranges during venipuncture were: No treatment 7 (5-10); sterile water group 7 (6-10); 30% glucose group 5 (3-7); 2 ml of 30% sucrose (0.6g) group 5 (2-8); pacifier alone group 2 (1-4); 2 ml of 30% (0.6 g) sucrose with pacifier group 1 (1-2). All groups had significantly lower pain scores compared to sterile water group: 30% glucose (p = 0.005), 2 ml of 30% (0.6 g) sucrose (p = 0.01), pacifier (p < 0.0001), 2 ml of 30% (0.6 g) sucrose with pacifer (p < 0.0001). Pacifier alone group had significantly lower pain scores than infants receiving 30% glucose (p = 0.0001) or 2 ml of 30% (0.6 g) sucrose (p = 0.001). Trend towards lower pain scores for infants receiving 2 ml of 30% (0.16 g) sucrose with pacifier compared to pacifier alone (p < 0.06)

33 preterm infants. Median (Range) gestational age of intervention group  30 (25-33). Median (Range) gestational age of control  group  31 (27-33)

Pain assessed at venipuncture phases (baseline, antisepsis, puncture, dressing, recovery). Sucrose administered before every minor painful procedure (venipuncture, arterial puncture, heel-lance, intravenous cannulation, endotracheal tube introduction, endotracheal tube suctioning, gavage insertion for feeding, removal of electrode leads and tape)

0.5 ml/kg  of sterile water 2 min prior to procedure

0.5 ml/kg  25% sucrose 2 min prior to procedure

Volume of solution was adjusted for current body weight

Incidence of cry

Heart Rate

Neonatal facial coding system (NFCS) score

Activated Behavioural State (ABS) score

Percentage

Percentage with rate greater than 160 beats per min (bpm)

Percentage attaining score equal to or greater than 3

Percentage attaining score equal to or greater than 4

On the second day there was a significant difference between the sucrose and control groups in the antisepsis phase (p = 0.04) and puncture phases (p = 0.009). On day 3, there was a significant difference between groups in the dressing phase (p = 0.04). On day 4, significant differences existed between groups at th puncture phase (p = 0.03). 

No significant differences in HR were observed.   

NFCS: A significant difference was seen between sucrose and control groups on day 2 at the puncture phase (p = 0.05) favouring the glucose group. A significant difference was also observed on day 3 at the antisepsis phase (p = 0.02) in favour of the sucrose group. At the dressing phase, the trend favoured the sucrose groups, but this result was not significant (p = 0.09). No significant differences were observed on day 4, but a trend favouring the sucrose group was noted in the  puncture (p = 0.08) and dressing (p= 0.09) phases.    

ABS: A significant difference was seen between sucrose and control groups on day 2 at the puncture phase (p = 0.05) favouring the sucrose group. A significant difference were also observed on day 3 at the antisepsis phase (p = 0.02) in favour of the glucose group. At the dressing phase, the trend favoured the sucrose groups, but this result was not significant (p= 0.09). No significant differences were observed on day 4, but a trend favouring the sucrose group was noted in the  puncture (p = 0.08) and dressing (p = 0.09) phases.

100 healthy full term infants

Heel lancegroup gestational age (GA) 40 weeks (range 38-42 weeks)

Heel lance + sucrose group GA 39 weeks (range 37-41 weeks)

Venipuncture group GA 39 weeks (range 37-41 weeks)

Venipuncture + sucrose group GA 39 weeks (range 37-41 weeks)

Heel lance (HL) or Venipuncture (VP)

Heel lance + 0.1 ml of sterile water on infant's tongue via syringe 2 min before procedure (n=25)

Heel lance + 0.1 ml of 50% sucrose on infant's tongue via syringe 2 min before procedure (n=25)

Venipuncture + 0.1 ml of sterile water on infant's tongue via syringe 2 min before procedure (n=25)

Venipuncture + 0.1 ml of 50% sucrose on infant's tongue via syringe 2 min before procedure (n=25)

Duration of first cry (sec), First crying time/total procedure time (%) and the ration of crying: no crying

NFCS score 1 min after oral administration of water/sucrose (1), disinfection of skin before HL or VP (2), during skin puncture (3), during blood sampling (4), during compression to stop bleeding (5), during application of plaster (6) and 1 min after application of plaster (7)

Reported Medians, range and Mean, SD

Reported in graph form, median and interquartile range

Significant reduction in duration of first cry in heel lance group given sucrose compared to heel lance alone, p < 0.05.

Significantly reduced NFCS scores in sucrose group during heel lance (median 47, interquartile range 31-60) and during compression to stop bleeding (median 32, interquartile range 8-54) compared to the water group (median 58 interquartile range 54-65, median 52, interquartile range 41-61 respectively) (p < 0.01).

Sucrose did not significantly reduce NFCS scores during or after venipuncture.

40 preterm infants, median gestational age (GA) 29 weeks (24-34 weeks)

Sterile water group: median GA 27 weeks, median postnatal age 45 days.

Sucrose group: median GA 29 weeks, median postnatal age 43 days

Water and pacifier group: median GA 30 weeks, median postnatal age 41 days

Sucrose and pacifier group: median GA 29 weeks, median postnatal age mean 42 days

Eye exam for retinopathy of prematurity

1 ml sterile water via a syringe into the mouth (n=10)

1 ml sucrose 33% via a syringe into the mouth (n=10)

1 ml sterile water via a syringe into the mouth and pacifier (n=9)

1 ml sucrose 33% via a syringe into the mouth and pacifier (n=11)

*all were given two minutes before start of  the eye exam*

Premature Infant Pain Profile (PIPP) during examination of eye

Mean, SD, 95% CI

Significant differences in PIPP scores between the groups, p = 0.023.

Infants in pacifier groups scored significantly lower than groups without pacifiers, p = 0.003 (95% CI -4.23, -0.96).

No significant differences between groups receiving sucrose vs. groups receiving water.

.

23 neonates, gestational age 24-29 weeks, postnatal age 28-93 days

Eye examination for Retinopathy of Prematurity (ROP)

2 ml of sterile water

2 ml of 24% sucrose (n=23, crossover design)

Mydriatic eye drops (Phenylephrine HCl 1% cyclopentolate HCl 0.2%) and local anaesthetic eye drops (proparacaine HCl 0.5%; 2 drops) given to both groups prior to exam

Decreased oxygen saturation by ≥10% preexamination, at eye speculum insertion and postexamination

PIPP scores at 5 min and 1 min pre-exam, eye speculum insertion, and 1 min and 5 min post-exam

Percentage of population

Means, SD reported

No significant difference in oxygen saturation between water group and sucrose group.

PIPP score at the eye exam significantly lower in the group given sucrose (mean 8.3, SD 4.5) compared to the placebo group (mean 10.5, SD 4.0), p = 0.01); however, this effect was not sustained at 1 and 5 min post-exam.

32 preterm infants, mean gestational age 28 weeks, mean postnatal age 50.8 days

Eye exam for retinopathy of prematurity

Sterile water delivered either directly into the mouth or via a nipple 2 min prior to eye exam (n=16)

24% oral sucrose was delivered either directly into the mouth or via a nipple 2 min prior to eye exam (n=16)

Doses were adjusted by weight

<1kg=0.5cm3 (0.12g); 1-1.5kg=1.0cm3 (0.24g); 1.5-2kg=1.5 cem3 (0.36g); >2kg=2.0cm3 (0.48g)

All infants were swaddled and offered a pacifier

All infants received tropicamide 0.5% and phenylephrine 2.5% eye drops approx. 30 min before exam. Topical tetracaine was instilled into the eyes just prior to the exam. 

% of the eye exam the infant spent crying 

Mean HR, at baseline, post-eye drop instillation, post-study drug, during eye exam and post eye exam*

RR and oxygen saturation at baseline, post-eye drop instillation, post-study drug, during eye exam and post eye exam*

PIPP at  baseline, during eye exam, post eye exam*

*measures are taken at 1 minute intervals and are averaged for each study period - study period times (in min) is not defined

Mean, SD

No significant difference in crying time between the sucrose and water groups.

Significant increases in HR, in both groups from baseline, p <0.01.

No differences between the sucrose and placebo groups in HR at any time point.

Significant reduction in oxygen saturation in infants receiving sucrose after the study drug (mean 95%, SD 4%) compared to the water group (mean 97%, SD 3%)

Significant reduction in oxygen saturation in infants receiving sucrose during the eye exam (mean 93%, SD 5%; p < 0.05) compared to the water group (mean 96% SD 3%; p < 0.05).

No significant difference in RR and oxygen saturation at two minutes post-exam.

No significant differences in PIPP scores between the sucrose and placebo groups before, during and after eye exams.

30 preterm infants

Water group: mean gestational age 27.3 weeks, mean postnatal age 8.2 weeks

Sucrose group: mean gestational age 26.5 weeks, mean postnatal age=8.5 weeks

Eye exam for retinopathy

Pacifier and 3 doses of 0.1 ml sterile water via syringe into the mouth (n=15)

Pacifier and 3 doses of 0.1 ml 24% sucrose via syringe into the mouth (n=15)

*1^st dose given 1.5 minutes before local anesthetic eye drops, 2^nd dose right at placement of the eye speculum, 3^rd dose 120s after 2^nd drop*

All infants received proparacaine hydrochloride 0.5% eye drops and were swaddled before the eye examination

PIPP at baseline, at eye drop instillation, at examination of left eye and at 30s, 60s, 90s and 120s after the exam

Mean, SEM

Statistically significant differences in mean PIPP scores were found between sucrose group (mean 8.8, Mean SE 0.7) and the water group (mean 11.4, Mean SE 0.6) during the eye examination p = 0.0077. However this was not sustained after the eye examination.

30 preterm infants <32 weeks gestational age (GA) or weighing <1500g

Control group mean GA 28.88 weeks (range 25-31 weeks)

Treatment group mean GA of 29.57 weeks (range 26-32 weeks)

Eye exam for retinopathy of prematurity (ROP)

Prior to exam: instillation of 0.5% proparacaine and 1% tropicamide,  then 15 minutes later eye drop instillation of 0.5% tropicamide, 2.5% phenylephrin and, 0.5% tropicamide.

Control group: no swaddling, no pacifier and no holding (n=16)

Treatment group: Swaddled in warm blanket 15 minutes prior to exam; given pacifier soaked in 24% sucrose solution and held by nurse until 15 minutes after examination (n=14)

Total crying time out of 5 minutes starting at the onset of the ROP exam

HR 30 min before eye drop instillation and 5 min before ROP exam, during exam, 5 min after exam

Oxygen saturation and RR at 30 min before eye drop instillation and 5 min before the ROP exam, oxygen saturation and RR at ROP (3 measurements) and oxygen saturation and RR 5 minutes after ROP exam

Reported Means and SEM

Not reported

Oxygen saturation means and SEM reported

RR not reported

No significant differences in crying time between treatment and control groups.

There was no significant difference in heart rate between groups.

No significant differences between treatment group and the control group for oxygen saturation and respiratory rate at any point.

285 term infants

Various age groups based on required immunizations. Age groups were:

2 weeks, 2 months, 4 months, 6 months, 15 months, and 18 months.

Only data for neonates at 2 weeks of age are included in this review.

Subcutaneous injection

2 ml 12% Sucrose

2 ml sterile water

No treatment

Cry duration (during and after procedure)

Mean, SD

Percent time crying

The overall P-value for percent time crying was significant (F= 5.92, p < 0.005). Pair wise comparisons of the percent time spent crying of sucrose and water groups versus the no treatment group show significant differences (p < 0.01 for both comparisons).

This was the only age group in which significant differences were observed between sucrose, water, and no treatment groups.

33 preterm neonates, mean (SD) gestational age at birth 30 weeks (6 days), gestational age at injection 32 weeks (6 days)

Subcutaneous Injections

Non-nutritive pacifier sucking (41 injections)

0.2-0.5 ml of 30% sucrose with pacifier (86 injections)

local application of EMLA with pacifier (71 injections)

0.2-0.5 ml of sucrose with EMLA and pacifier (67 injections)

Duration of cry from needle introduction until to 2 minutes after its removal

Heart rate (HR) before injection, during injection and after injection

Oxygen saturation before injection, during injections and after injection

Douler Aigue Du Nouveau-ne (DAN) and Neonatal Facial Coding System (NFCS) scores during injection

Mean, SD

Crying time was significantly lower in the sucrose + EMLA+ Pacifier group (p = 0.0002). The mean (SD) crying time in each group was as follows: 3.93 sec (2.97) in the pacifer only group, 2.81 sec (4.81) in the EMLA + Pacifier group, 2.32 sec (7.51) in the sucrose + pacifier group and 0.89 sec (2.66) in the sucrose with EMLA +Pacifier group.

There were no significant differences in HR between the four groups

The only significant difference in oxygen saturation between groups occurred during injection, which was lower in the NNS group (p = 0.02)

Significant reduction in DAN and NFCS scores in EMLA+NNS, sucrose+NNS, and sucrose+ EMLA+Pacfier groups compared to NNS alone.

20 infants,

Mean (SD) gestational age 30.7 weeks (2.3)

NG tube (NGT) insertion

0.5 - 2 ml of Sterile water 2 min prior to procedure

0.5 - 2 ml 24% sucrose 2 min prior to procedure

Volume of solution was adjusted for current body weight

> 2kg = 2 ml

1.5kg to 2kg = 1.5 ml

<1.5kg = 0.5 ml

Incidence of cry

Baseline heart rate and change in HR from baseline during NGT insertion

Baseline oxygen saturation and change in oxygen saturation from baseline during NGT insertion

Neonatal Facial Coding Score (NFCS) during NGT insertion and after insertion

Percentage

Mean, SD

Median

There was a non-significant trend (p = 0.069) for fewer sucrose-treated infants to cry during NGT insertion (8/26), compared with the placebo group (14/25).

Infants in the sucrose group had higher mean pretreatment baseline heart rate than placebo group but showed no change in heart rate during NGT insertion (mean change -0.7 bpm). The placebo groups heart rate increased during NFT insertion (mean change +11). This difference approached statistical significance (p = 0.055)

No significant changes in mean oxygen saturation occurred in either groups.

Sucrose group had a significant lower median NFCS score during NGT insertion compared with the water group [1(range 0-4) vs. 3 (range 0-4), median difference 1 (95% CI 0 to 2) p = 0.004].

After NGT insertion, the NFCS scores fell to a median of 0 in both groups.

To see if NFCS is specific for pain, authors analyzed the 4 components on their own. Nasolabial folds showed a significant inhibition in the sucrose group [present in 4/26 or (15%) compared with 12/25 (48%) in the placebo group; p = 0.012].

120 healthy male newborns, gestational age 38 weeks or greater

Circumcision

Control group - no treatment (n=40)

Dorsal Penile Nerve Block (DPNB) - 0.8 ml of 1% lidocaine without epinephrine injected into dorsolateral penile root 3 min before procedure (n=40)

Pacifier dipped in 50% sucrose with a gauze pad moistened with sucrose inside the nipple 2 min before procedure (n=39)

Heart rate (HR) at baseline, restraint, skin preparation for procedure, lateral clamping, lysis of adhesions, dorsal clamping, dorsal cut, retraction, application of Gomco bell and clamp, tightening of clamp, excision of foreskin, removal of clamp, removal of bell, placement of dressing and overall change in heart rate from baseline

Oxygen saturation at baseline and throughout procedure; change from baseline during the circumcision procedure

Mean, SD, mean differences and 95% CI

Mean change in HR from baseline through all follow-up times were significantly different between groups (p-values < 0.001).

Mean HR differences + 95% CIs: control vs. DPNB, 27.1 bpm (17.6, 36.6), control vs. sucrose, 9.7 bpm (0.1, 19.3), and sucrose vs. DPNB, 17.4 bpm (7.8, 27.0).

Sucrose had statistically significant effect compared to the no treatment controls (p < 0.001)

Significant differences between groups in changes in oxygen saturation from baseline to circumcision ( P < .001).

Mean oxygen saturation differences + 95% CI between the 3 groups from baseline: -2.5 (-15.8 to 3.12) for the control group, -0.8 (-4.3 to 5.5) for the DPNB group and 0.7 (-6.8 to 12.5) for the sucrose group.

Differences between both the DPNB and sucrose groups compared to control were significant (p < 0.05)

Control vs. sucrose, -3.3 (-5.0 to -1.6) was statisically significant (p < 0.001)

57 term infants, mean age at time of procedure 30-43 hours

Circumcision

Gomco method and pacifier dipped in water (n=14)

Gomco method and pacifier dipped in 24% sucrose (n=14)

Mogen method and pacifier dipped in water (n=15)

Mogen method and pacifier dipped in 24% sucrose (n=14)

All infants had EMLA cream applied 1-3 hours before procedure

Time spent crying during procedure

Time spent grimicing

Procedure stages:

1) Table - Restraint,

2) Restraint - Forceps,

3) Forceps - Excision,

4) Excision - Unrestraint

5) Unrestraint - End

Median and Means, Graphically

Not reported

Cumulative mean time crying for forceps to unrestraint interval in the Gomco-sucrose group was 56 seconds (median = 53 sec) compared to 86 seconds (median = 78 sec) in the Gomco-water group ( p = 0.0001). Crying time in Mogen-sucrose and Mogen-water groups were not significantly different.

Overall, mean crying time significantly decreased in infants treated with sucrose compared to infants treated with water (p = 0.0001).

Significantly less time spent grimacing in the Gomco-sucrose group compared to the Gomco-water group (p = 0.0001).

No significant differences between Mogen-sucrose and the Mogen-water groups.

Overall, mean time grimacing was significantly reduced in infants treated with sucrose compared to infants treated with water (p = 0.0001).

80 healthy term newborn male infants, mean gestational age 39.5 weeks

Circumcision

Dorsal Penile Nerve Block (DPNB) (0.8 ml lidocaine and 0.2 ml saline) plus pacifier dipped in water and using new padded restraint chair

DPNB with buffer (0.8 ml of lidocaine and 0.2 ml of sodium bicarbonate) and pacifier dipped in water

DPNB (0.8 ml lidocaine and 0.2 ml saline) and pacifier dipped in 24% sucrose

Control: DPNB (0.8 ml lidocaine and 0.2 ml saline) and pacifier dipped in water

Plasma cortisol level 30 minutes after beginning circumcision

Mean, SD

Plasma cortisol levels not significantly different between groups.

80 infants less than or equal to 90 days of age requiring bladder catheterization

Subgroup analysis performed: infants 1-30, 31-60, and 61-90 days of age

Bladder Catheterization

2 ml of sterile water via syringe 2 min before procedure (n=40)

2 ml of 24% sucrose via syringe 2 min before procedure (n=40)

Percentage of subjects crying at maximal insertion (%)

Percentage

Subgroup analysis of infants (1-30 days) receiving sucrose were significantly less likely to cry during maximal catheter insertion compared to water group (28.6%, vs. 78.6%, p = 0.008).

103 infants, GA < 31 weeks (57 infants included in this analysis)

All painful procedures during the 1st week of life

Before every painful procedure, up to 3 doses of:

0.1 ml of 24% sucrose (n=27)

0.1 ml of sterile water (n=30)

Salivary cortisol levels at baseline, 30 minutes after painful procedure at days 1,3,5,7

Mean, SD

No significant differences between groups for mean cortisol levels at baseline or post painful procedures.

240 newborn infants born to non-diabetic and diabetic mothers, gestational age greater than or equal to 36 weeks

3 heel lances, venipuncture and intramuscular vitamin K injection

2 ml of 24% sucrose given to infants of non-diabetic mothers (n=60)

2 ml of 24% sucrose given to infants of diabetic mothers (n=60)

2 ml of sterile water given to infants of non-diabetic mothers (n=60)

2 ml of sterile water given to infants of diabetic mothers (n=60)

PIPP scores overall, during intramuscular injection, during venipuncture and all three heel lances

Mean, SD, 95% CI

Overall PIPP scores significantly lower among newborns given sucrose (mean 6.8, SD 2.9) compared to placebo (mean 8.1, SD 2.5) (mean difference-1.3, 95% CI -2.0 to -0.6, p < 0.001).

PIPP scores during intramuscular injection did not differ between the sucrose and placebo group for non-diabetic or diabetic mothers.

PIPP score during venipuncture was significantly lower among infants of non-diabetic mothers who received sucrose compared to placebo (mean score 5.7, 95% CI 4.7-6.7 vs. mean score 8.9, 95% CI 7.9-9.9, p < 0.001). Similar results were found among infants of diabetic mothers (sucrose: mean score 6.8, 95% CI 5.7-7.9 vs. placebo: mean score 9.2, 95% CI 8.4-10.1, p < 0.001).

During first 3 heel lances, newborns from diabetic mothers receiving sucrose or placebo did not have significantly different PIPP scores