L Aliwalas
Protocol writing
Review writing
Identification of
studies
Entering data in Revman
Revision of review
V Shah
Protocol editing
Review editing
Checking the search for
trials
Identification of studies
Checking the data in Revman
Clinical studies have shown beneficial effects of pre-emptive analgesic administration in decreasing neonatal pain and stress (Anand 1989). Pharmacological interventions include acetaminophen, sucrose and opioid analgesics. Nonpharmacological interventions include reduction of noxious stimuli (Schechter 1997), implementation of neurobehaviorally supportive relationship-based care (Corff 1995; Gunnar 1984), limitation of the number of painful procedures (Anand 2001) and breastfeeding during the actual procedure.
There are several potential mechanisms by which breast milk or breast feeding might provide an analgesic effect. Components of breast feeding that may be analgesic include presence of a comforting person (mother) (Blass 1995), physical sensation (skin to skin contact with comforting person) (Blass 1995), diversion of attention (Gunnar 1984) and sweetness of breast milk (presence of lactose or other ingredients present in the breast milk) (Blass 1997). Compared to artificial formulas, breast milk contains a higher concentration of tryptophan (Heine 1999), a precursor of melatonin. Melatonin is shown to increase the concentration of beta endorphins (Barrett 2000) and could possibly be one of the mechanisms for the nociceptive effects of breast milk. Preterm neonates incapable of direct breastfeeding from the mother may benefit from placement of breast milk on the tongue or administering breast milk via the naso/orogastric route (supplemental breast milk) through some of the mechanisms listed above. Among the analgesics studied for neonatal pain, breastfeeding/breast milk is a natural, easily available, easy to use and potentially risk free (Schollin 2004) intervention. It is an intervention that could be easily adopted from the perspectives of health care providers and parents. No adverse effects of breastfeeding apart from rare transmission of micro-organisms have been reported.
In a systematic review, 24% sucrose was found to be effective in alleviating procedural pain in neonates (Stevens 2004). Both opioid and non-opioid mechanisms were suggested for its effectiveness. Breast milk contains only 7% lactose and may not be as effective as sucrose. On the other hand, interventions like pacifiers or positioning may result in an effect similar to breastfeeding or supplemental breast milk without interruption of the regular breastfeeding schedule.
To our knowledge, the topic of breastfeeding or breast milk for procedural pain in neonates has not been systematically evaluated.
Specific objectives were:
Primary
1. Compare breastfeeding with control (placebo, no
treatment, sucrose, glucose, pacifiers or positioning)
2. Compare breast milk
with control (placebo, no treatment, sucrose, glucose, pacifiers or
positioning)
Secondary
Within each comparison, to conduct subgroup analyses
according to:
1. Types of control intervention: placebo, no treatment,
sucrose, glucose, pacifiers and positioning
2. Type of painful procedure:
heel lance and venepuncture
3. Gestational age: preterm (< 37 weeks) and
full term (> 37 weeks)
Within the group of supplemental breast milk, subgroup analysis based on the amount of breast milk was planned to be carried out if data were available.
2. Cry variables:
a. Percentage time crying
b. Duration of crying (in
seconds)
3. Validated pain measures:
a. Neonatal Infant Pain Score (Lawrence 1993)
b.
Premature Infant Pain Profile (PIPP score) (Stevens 1996)
c.
Neonatal Facial Coding System (NFCS) (Craig 1994)
d. Other
pain scores as reported: We identified during this review that other
non-validated scores such as Douleur Aigue Nouveau-né score (DAN) (Carbajal 2003);
composite score (Shendurnikar
2005), body pain score (Bucher 2000) and
visual analogue scale (VAS) (Gradin 2004) were
reported by authors and have been reported in this review.
Secondary outcomes
1. Any clinically important outcome reported by authors (not
pre-specified)
2. Any harmful effects reported by any author
Population: Infant-Newborn (MeSH) OR Infant-premature (MeSH) OR
Infant, Low Birth Weight (MeSH) OR Infant, Very Low Birth Weight (MeSH) OR
Infant, Small for Gestational Age (MeSH) OR Infant, Premature, Disease (MeSH) OR
Infant, Newborn, Diseases (MeSH) OR newborn (text word) OR infant (text word) OR
neonate (text word)
Intervention: Breast (MeSH) OR Breast Feeding
(MeSH) OR Milk, Human (MeSH) OR Breast Milk (MeSH) OR Human, Milk (MeSH)
Comparison: Clinical trials (MeSH) OR Controlled Clinical Trials
(MeSH) OR Randomized Controlled Trials (MeSH) OR Random Allocation (MeSH) OR
Multicenter studies (MeSH) OR Control groups (MeSH) OR Evaluation studies
(MeSH)
Outcome: Pain (MeSH) OR Pain Measures (MeSH) OR Pain
measurement (MeSH)
Other databases that were searched include: EMBASE (1980 - Feb 2006); CINAHL (1982 - Feb 2006); the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005) and the reference lists of identified trials, abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1994 - 2006) and major pediatric pain conference proceedings. Reference lists of the identified articles were searched. No language restrictions were applied.
The following types of articles were excluded: letters (which do not contain original data), editorials, reviews, lectures and commentaries.
Quality of included trials was evaluated independently by all review authors
using the following criteria:
1. Masking of randomization
2. Masking of
intervention
3. Completeness of followup
4. Masking of outcome
assessment
There were three potential answers to these questions - yes, no
and can't tell.
The data were compared for the outcomes outlined in the previous section as follows (planned primary and subgroup analyses):
Comparison 1: Breastfeeding vs. control (The infant
must be actually feeding from the breast at the time of
intervention)
Category 1: Type of control intervention
Subgroups: A.
Breastfeeding vs. placebo, B. Breastfeeding vs. no treatment, C. Breastfeeding
vs. sucrose or glucose, D. Breastfeeding vs. pacifiers E. Breastfeeding vs.
positioning
Category 2: Type of procedure
Subgroups: 1. Heel lance 2. Venepuncture
Category 3: Gestational age
Subgroups 1: Preterm (< 37 weeks
gestational age) 2. Term (> 37 weeks gestation age)
Comparison 2: Supplemental breast milk vs. control
(The infant may be receiving breast milk via oral or nasogastric tube
in the intervention group)
Category 1: Type of control
intervention
Subgroups: A. Supplemental breast milk vs. placebo, B.
Supplemental breast milk vs. no treatment, C. Supplemental breast milk vs.
sucrose or glucose, D. Supplemental breast milk vs. pacifiers E. Supplemental
breast milk vs. positioning
Category 2: Type of procedure
Subgroups: 1. Heel lance 2. Venepuncture
Category 3: Gestational age
Subgroups 1. Preterm (< 37 weeks
gestational age) 2. Term (> 37 weeks gestation age)
RevMan 4.2 was used for statistical analysis. Statistical parameters included relative risk (RR), risk difference (RD), number needed to treat (NNT), number needed to harm (NNH) and weighted mean difference (WMD) when appropriate. Ninety-five percent confidence intervals (CI) were reported for estimates of treatment effects. A fixed effect model was used for meta-analyses. Tests for between study heterogeneity including the I2 test was applied to assess the appropriateness of combining studies.
Post-hoc subgroups for comparison were added when it was identified that
comparison of breastfeeding or supplemental breast milk have been reported with
artificial sweetener and glycine.
Blass 2001
compared the effects of supplemental breast milk (colostrum) to water and
sucrose. This was a quasi-randomized controlled trial of 60 full-term infants.
The infants were randomly assigned to one of the following groups (10 neonates
in each group):
Group 1: water via syringe;
Group 2: colostrum via
syringe;
Group 3: sucrose via syringe;
Group 4: water on a pacifier;
Group 5: colostrum on a pacifier and Group 6: sucrose on a pacifier.
The
infants were between 30 - 55 hrs of age at the time of blood collection for
routine neonatal screening using the heel lance procedure. Two ml of the
allocated solution was given either by slow administration via syringe over a
span of two minutes or by allowing infant to suck a pacifier dipped in the
solution every 30 seconds for two minutes. Prior to the procedure, baseline data
were obtained for 60 seconds and continuous monitoring was done throughout and
after the procedure during the recovery time. The blood collection was done by
an experienced phlebotomist for 49 of the 60 infants. The outcomes measured were
reduction in the percentage crying and grimacing times during the procedure; the
mean crying time following the procedure and the mean heart rate change during
and following the procedure. Despite repeated requests, data regarding
individual groups were not obtained from the authors.
Bucher 2000
compared the effects of commercially available artificial sweetener (containing
10 parts cyclamate and one part saccharin) to glycine (sweet amino acid),
expressed breast milk and sterile water. This was a randomized controlled trial
of 80 full-term infants. The infants were randomly assigned to one of the
following groups (20 neonates in each group):
Group 1: 2 ml of artificial
sweetener via syringe;
Group 2: 2 ml of glycine via syringe;
Group 3: 2
ml of breast milk via syringe;
Group 4: 2 ml of sterile water via syringe.
The infants were studied on postnatal day four at the time of blood
collection for routine neonatal screening using the heel lance procedure. Two ml
of the allocated solution was given via syringe on the anterior part of tongue
by a nurse not involved in the study. Prior to the procedure, baseline data were
obtained and continuous monitoring was done throughout and after the procedure
during the recovery time. The blood collection was performed two minutes after
administration of solution by a research nurse. The procedure was video taped
and evaluated by two independent observers unaware of allocation. The outcomes
measured were heart rate change, percentage time crying, body pain score, facial
pain score (five components of NFCS) and body pain score (torso movements 1 =
one side, 2 = both sides; head movements = 1; arm movements 1 = one arm, 2 =
both arms; hand movements 1 = one hand, 2 = both hands; bringing hands to face
(mouth) = 1 point; maximum score was 8 points, minimum score was 0 points)
during and after blood collection. The data were presented in graphical format.
Numerical data were obtained by contacting the author.
Carbajal 2003
compared the effects of breastfeeding to positioning, sterile water and 30%
glucose. This was a randomized controlled trial of 180 term neonates. The
infants were randomized to one of the four groups:
Group 1: breastfeeding (n
= 44);
Group 2: held in mother's arms without breastfeeding (n = 45);
Group 3: sterile water without pacifier (n = 45);
Group 4: 30% glucose
followed by a pacifier (n = 45).
In Group 1 and 2, the interventions were
started two minutes before the procedure and continued throughout the procedure.
In groups 3 and 4 the intervention was commenced two minutes prior to the
procedure respectively. Venepuncture was performed when infants were at least 24
hours of age and had not been fed for the previous 30 minutes. The
primary outcome measure was the DAN scale (Carbajal 1997), a
behavioral scale developed to rate acute pain in term and preterm neonates. The
score comprised of three items namely facial expressions, limb movements, and
vocal expression with values in each ranging from zero (no pain) to 10 (maximum
pain). The secondary outcome measure was the PIPP score. Mothers were
interviewed 48 - 72 hours after the study by standardized questionnaires to
assess any change in the sucking behavior. One infant was excluded from the
analysis as the outcome measure could not be assessed properly due to the
mother's head partially covering her infant's face. Data from all four groups
were used in their respective appropriate comparisons.
Gradin 2004
compared the effects of breastfeeding to sterile water and 30% glucose. This was
a randomized controlled trial of 120 full term neonates. The infants were
randomized to four groups:
Group 1: breastfeeding and 1 ml of sterile water
(n = 27);
Group 2: breastfeeding and 1 ml of 30% glucose (n = 29);
Group
3: fasting and 1 ml of sterile water (n = 26);
Group 4: fasting and 1 ml of
30% glucose (n = 29).
Infants underwent routine neonatal screening procedure
using venepuncture at 3 - 5 days of age. The data from the Group 3 were not used
for this review. For the breast fed group, the infants were allowed
breastfeeding ad libitum 45 minutes prior to blood sampling while infants
in the fasting group had blood sampling performed at least two hours after the
last feeding. One ml of either sterile water or 30% glucose was administered
through a syringe into the infants mouth, and one minute later the blood
sampling was performed. After sampling the infants were left undisturbed for
three minutes during recovery phase. The outcomes measured were the PIPP score
and mean crying time. Parents were asked to assess pain using a Visual Analogue
Scale (VAS). The agreement between the parental assessment of pain and the PIPP
score and crying time was determined. The primary author provided missing data.
Nine infants were excluded from the study by the authors mostly due to technical
problems with the video recordings (n = 6) and maternal choice to withdraw their
infants from the study (n = 3). Data from group 1, 3 and 4 were used for this
review as the combination of breastfeeding and glucose was not planned to be
compared a priori.
Gray 2002 compared
the effects of breastfeeding to positioning. This was a randomized controlled
trial of 30 full term neonates. The infants were randomized to two groups (15
neonates in each group):
Group 1: breast fed and cuddled with full body skin
to skin contact;
Group 2: swaddled and placed on their side in the crib.
All infants underwent heel lance for routine neonatal screening procedure.
Mean postnatal age at procedure was 46 hours in Group 1 and 40 hours in Group 2.
The outcomes measured were differences in crying, grimacing and heart rate
between the two groups before, during and after blood collection. The primary
author provided additional information.
Ors 1999 compared
the effects of supplemental breast milk to water and 25% sucrose. This was a
randomized controlled trial of 102 healthy term neonates. The infants were
randomized to three groups:
Group 1: received 2 ml of 25% sucrose (n = 35);
Group 2: received 2 ml of human milk (n = 33);
Group 3: received 2 ml of
sterile water (n = 34).
All infants underwent heel lance blood sampling by a
single performer. The allocated solution was given by syringe into the baby's
mouth over one minute. The heel prick was performed two minutes after
administration of the solution. Crying duration and heart rate at three minutes
were recorded from the time of the heel prick. The outcomes measured were crying
time, percentage change in heart rate and recovery time for the heart rate. The
primary author provided additional information. Data from all three groups were
used for this review in their respective appropriate comparisons.
Phillips 2005
compared the effects of breastfeeding in three groups in a randomized controlled
trial of 96 healthy term neonates:
Group 1: Breastfeeding (n = 32);
Group
2: neonates held by mother holding pacifier in infant's mouth (n = 39);
Group
3: neonates held by research assistant holding pacifier in infant's mouth (n =
25).
All infants underwent heel lance blood sampling by a single performer.
Mothers held babies in their bed while giving pacifier (group 2) while research
assistant held infants in bedside chairs (group 3). The outcomes measured were
crying duration, percentage of infants crying, changes in the heart rate, blood
pressure and oxygen saturation. The primary author provided additional
information. The purpose of studying three groups was to assess the differences
in outcome measures caused by one of the component of the act of breastfeeding
(maternal contact).
Shendurnikar
2005 compared the effects of breastfeeding to positioning (swaddling). The
authors provided details about the study as it was published as a letter to the
editor. This was a randomized controlled trial of 100 full term neonates. The
infants were randomized to two groups (50 neonates in each group):
Group 1:
breastfeeding group;
Group 2: swaddled and placed on a cradle.
Infants in
group 1 were breastfed for 15 minutes prior to heel prick. All infants underwent
heel lance procedure for clinical indication such as measurement of packed cell
volume or bilirubin. The outcomes measured were behavioral (state of arousal,
cry, facial expression, body movements); physiological (breathing pattern, heart
rate) and composite score (non validated) between the two groups before, during
and after blood collection. The primary author provided additional information.
The composite score was calculated using the following criteria:
(a) heart
rate (0 = < 120/minute; 1 = 120 - 160/minute and 2 = > 160/minute)
(b)
breathing (0 = relaxed; 1 = changed)
(c) facial expression (0 = relaxed; 1 =
grimaced)
(d) body movements (0 = relaxed; 1 = no gross movement; 2 = gross
body movement)
(e) state of arousal (0 = sleepy; 1 = awake; 2 = fussy)
(f)
cry (0 = no; 1 = whimper; 2 = vigorous) and combining the score.
The minimum
score was 0 and maximum score was 10. This study was published as a letter to
editor and authors provided additional data.
Skogsdal 1997
compared the effects of no intervention to 30% oral glucose, 10% oral glucose
and breast milk. This was a randomized controlled trial of 120 neonates (66
preterm neonates between 30-37 weeks and 54 term neonates). The infants were
randomly assigned to one of the following groups (30 neonates in each group):
Group 1: no intervention;
Group 2: 1 ml of 30% glucose via syringe;
Group 3: 1 ml of 10% glucose via syringe;
Group 4: 1 ml of breast milk
via syringe.
The infants were studied on mean (SD) postnatal day of five at
the time of blood collection for their routine care using the heel lance
procedure. One ml of the allocated solution was given via syringe by a nurse not
aware of allocation. Prior to the procedure, baseline data were obtained and
continuous monitoring was done throughout and after the procedure during the
recovery time. The blood collection was performed two minutes after
administration of solution. The outcomes measured were heart rate change and
duration of crying. The data were presented in graphical format, however,
contact author provided the data necessary for the review. As this study had two
comparative groups with different concentrations of glucose, for the purpose of
analyses the group who received 30% glucose was combined with data from Ors 1999 study where they
used 25% sucrose in one group (presuming very minimal difference in pain
responses between 25 and 30% sugar solution). The group who received 10% glucose
was compared with breast milk group separately.
Upadhyay 2004
compared the effects of supplemental breast milk to sterile water. This was a
randomized controlled trial of 87 full term neonates. The infants were
randomized to two groups:
Group 1: received 5 ml of expressed breast milk (n
= 40);
Group 2: received 5 ml of distilled water (n = 41) prior to
venepuncture.
Venepuncture was performed based on clinical indications.
Three babies from each group were excluded from the study by the authors due to
venepuncture failure and failure to attain state 3 or 4 of wakefulness. Data
from 81 infants were analyzed. The primary outcome was the duration of the cry
after the venepuncture. The secondary outcomes included changes in physiological
parameters namely heart rate and oxygen saturation from baseline to one and
three minutes after venepuncture and the modified NFCS. Only five easily
recordable parameters of the NFCS (out of ten) were assessed by investigators.
Data on heart rate, oxygen saturation were provided as mean and standard
deviation at baseline and three minutes. Authors were contacted to provide data
on mean changes in these parameters, but no response was obtained. The mean
difference and standard deviation of the difference were calculated assuming 50%
correlation between baseline and subsequent findings by the review authors.
Uyan 2005 compared
the effects of supplemental breast milk (two groups foremilk and hindmilk) to
water. This was a quasi-randomized controlled trial of 62 healthy term neonates.
The infants were randomized to three groups:
Group 1: received 2 ml of
foremilk (n = 20);
Group 2: received 2 ml of hindmilk (n = 21);
Group 3:
received 2 ml of sterile water (n = 21).
All infants underwent heel lance
blood sampling by single performer. The allocated solution was given by syringe
into the baby's mouth. The heel prick was performed two minutes after
administration of the solution. Crying duration and heart rate changes at one,
two, and three minutes were recorded from the time of the heel prick. The
outcomes measured were crying time, percentage change in heart rate and NFCS at
one, two and three minutes. The data from the group 1 and 2 were combined for
the analyses. Authors provided data on combined groups.
Blass 2001: The infants were initially assessed to determine whether they were successfully breastfed or not and then randomized into the colostrum groups and non-colostrum groups. Investigators initially planned the assignment of the infants based on a table of random numbers. Group assignment needed to be adjusted because some mothers were unable to obtain sufficient colostrum. After passing the exclusion criteria, investigators assessed mother's success regarding breastfeeding. If the mother was unsuccessful, she was assigned to groups that didn't involve breast milk (group 1, 3, 4 and 6). If breastfeeding was established the infant was assigned to group 2 or 5. The phlebotomist who performed the heel-lance was unaware of allocation, study's purpose or hypotheses. The authors did not define what constituted successful breastfeeding. The data collection for sucrose, water and pacifier groups completed in June 1998, while colostrum data collection ended in March 1999. Although the phlebotomist and the person who rated video data were unaware of treatment allocation, this could have introduced a degree of bias. Masking of intervention was not possible in this study since it involved the use of a pacifier and a liquid (colostrum) that differed in color from two other solutions. Masking of outcome assessment was possible with crying time and heart rate changes, but not so when assessing the grimacing since the intervention involved the use of a pacifier. A number of infants in the water and colostrum groups were excused (data collection not continued and infant allowed to be comforted in other ways) after 90 seconds of recovery period due to excessive crying, though all infants were included in the final analysis with the assumption that these behaviors would have continued at the same level for the rest of the recovery period.
Bucher 2000: The randomization was done through sealed envelopes. One nurse administered solution in the absence of investigators and was not involved in heel prick or data collection. Masking of outcome assessment was done by blinding observer as to the assignments to the study group.
Carbajal 2003: The randomization was done by research assistant using numbered envelopes. Allocation was concealed from the investigators. Masking of the intervention was not possible in this study since it involved breastfeeding, the use of a pacifier and cuddling before and throughout the procedure. The outcome assessment was masked as the observers who assessed the outcome measures were not aware as to the purpose and hypothesis of the study. However, personal bias on the part of outcome observer could not be excluded.
Gradin 2004: The randomization was done through sealed envelopes. The intervention involved the use of placebo to mask the solution in question. Masking of outcome assessment was done by blinding observer as to the assignments to the study group.
Gray 2002: The randomization was done through sealed envelopes. The masking of intervention was not possible since it involved breastfeeding before and throughout the procedure. Masking of outcome assessment was also not possible. All participants were accounted for in the analysis of outcomes.
Ors 1999: The manner of randomization was not discussed by the authors. Masking of the intervention was made possible by using a placebo and by performing the heel prick one minute after giving the solutions. The two investigators who analyzed the data were unaware of the treatment intervention, hence, the outcome measure analysis was blinded. All infants were accounted for in the analysis.
Phillips 2005: The randomization was done through envelopes containing allocation cards. Masking of intervention was not possible since it involved breastfeeding before and throughout the procedure. Masking of outcome assessment (from video recordings) was not done; however, data from monitors (heart rate, saturation and blood pressure) were analyzed in a masked manner. All participants were accounted for in the analysis of outcomes; however, for some analyses complete data were not available from all patients.
Shendurnikar 2005: Primary author provided this information. The randomization was done by the primary author asking mother to choose from a collection of randomization cards. The masking of intervention was not possible since it involved breastfeeding before and throughout the procedure. Masking of outcome assessment was not done and primary author collecting data was aware of the allocation and hypothesis of the study. All participants were accounted for in the analysis of outcomes.
Skogsdal 1997: The randomization was done through random digit table. The heel prick and administration of allocated solution was done by the same nurse. Outcome data collection was done by a different nurse who was unaware of allocation. All participants were accounted for in the analysis of outcomes.
Upadhyay 2004: The randomization was performed using computer generated numbers. Allocation was adequately concealed. The observers were blinded as to the intervention given to the infants. The data of the 81 subjects were available for analysis because in six infants, either there was technical problem or the infants were not fully awake.
Uyan 2005: The authors provided further information on method of randomization indicating that it was quasi-randomized (based on number or day of the procedure). According to authors the intervention was masked. The two investigators who analyzed the data and the person who recorded video for the NFCS coding were unaware of the treatment allocation; hence, the outcome measure analysis was blinded. All infants were accounted for in the analysis.
Comparison 1: Breastfeeding vs. control
Five studies reported on this comparison (Carbajal 2003; Gray 2002; Gradin 2004; Phillips 2005; Shendurnikar 2005).
1. Physiological parameters
a. Outcome 01.01: Heart rate change (bests per minute)
Two studies (Gray 2002; Phillips 2005) reported on the heart rate change during heel lance. The heart rate tended to increase in both groups during the procedure, but the increase was significantly lower in the breastfeeding group compared to the swaddled group (Gray 2002) (mean difference [MD] -23; 95% confidence interval [CI] -35 to -11) and the breastfeeding group and group of infants held by mother holding a pacifier in the infant's mouth (Phillips 2005) (mean difference -11; 95% CI -21 to -1). There was no statistically significant difference in heart rate change between breastfeeding group and group of infants held by research assistant along with the use of pacifier (Phillips 2005) (MD -7; 95% CI -15, 1).
b. Changes in the respiratory rate
None of the studies included in this review reported on this outcome.
c. Outcome 01.02: Oxygen saturation change
One study (Phillips 2005)
reported on the oxygen saturation change during heel lance. There was no
difference in oxygen saturation change between the breastfeeding group and the
group of infants held by mother holding a pacifier in the infant's mouth (MD
0.3; 95% CI -2.8, 3.4) and between the breastfeeding group and group of infants
held by research assistant holding a pacifier in the infant's mouth (MD 0.6 95%
CI -1.5, 2.7).
d. Outcome 01.03: Blood pressure changes
One study (Phillips 2005) reported on the blood pressure change during heel lance. There was no difference in blood pressure change between the breastfeeding group and the group of infants held by mother holding a pacifier in the infant's mouth (MD -3.6; 95% CI -9.1, 1.9) and the breastfeeding group and the group of infants held by research assistant holding a pacifier in the infant's mouth (MD 1.6 95% CI -4.9, 8.1).
2. Cry variables
a. Outcome 01.04: Percentage of time crying
Two studies (Gray 2002; Phillips 2005) reported percentage of time crying during heel lance. There was statistically significant reduction in the percentage time crying among infants in the breastfeeding group compared to the swaddled group (Gray 2002) (MD -39; 95% CI -55 to -23) and infants in the breastfeeding group compared to the group of infants held by research assistant holding a pacifier in the infant's mouth (Phillips 2005) (MD -33; 95% CI -50, -13). There was no statistically significant reduction in the percentage time crying between the breastfeeding group and the group of infants held by mothers holding a pacifier in the infant's mouth (Phillips 2005) (MD -12; 95% CI -28, 4).
b. Outcome 01.05: Duration of crying in seconds
Two studies (Gradin 2004; Gray 2002) reported on the duration of crying. Infants in the breastfeeding group compared to the fasting group had a significant reduction in the duration of crying (Gradin 2004) (MD -50; 95% CI -79 to -22 sec). However, for infants in the breastfeeding group compared to the group given glucose, there was no statistically significant difference in the duration of crying (Gradin 2004) (MD -5; 95% CI -37 to 26 sec). Infants in the breastfeeding group compared to the swaddled group had a statistically significantly reduced duration of crying during heel lance (Gray 2002) (MD -63; 95% CI -75 to -52 sec).
Phillips 2005 reported that 69% of infants in the breastfeeding group cried during the procedure compared to 81% of the infants in the group held by mothers with pacifier use and 100% of infants in the group held by a research assistant and use of pacifier (p < 0.01).
3. Validated pain measures
a. Neonatal Infant Pain Score
None of the studies included in this review reported on this outcome.
b. Outcome 01.06: Premature Infant Pain Profile (PIPP) Score
Two studies reported on the PIPP scores (Carbajal 2003; Gradin 2004). The PIPP scores in the breastfeeding group were significantly lower compared to placebo group (MD -6; 95% CI -7 to -4) or the positioning in mother's arms group (MD -7; 95% CI -9 to -6). The PIPP score between breastfeeding and no treatment group was not statistically significantly different (MD 0; 95% CI -2 to 1). PIPP score was statistically significantly higher in the breastfeeding group compared to glucose group (MD 1.30; 95% CI 0.05 to 2.56).
c. Neonatal Facial Coding Score (NFCS)
None of the studies included in this review reported on this outcome.
d. Other pain scores as reported (non validated):
i. Outcome 01.07: Douleur Aigue Nouveau-né score (DAN) Scale
Only one study reported on DAN score (Carbajal 2003). The DAN scores in the breastfeeding group compared to placebo (MD -6; 95% CI -7 to -5) and breastfeeding group compared to positioning in mother's arms group (MD -7; 95% CI -8 to -6) were statistically significantly lower. The DAN score between breastfeeding group and glucose group was not statistically significantly different (MD -0.8; 95% CI -2.0 to 0.5).
ii. Outcome 01.08: Composite score
Shendurnikar
2005 calculated composite score. The composite score was calculated using
the following criteria:
(a) heart rate (0 = < 120/minute; 1 = 120 -
160/minute and 2 = > 160/minute)
(b) breathing (0 = relaxed; 1 =
changed)
(c) facial expression (0 = relaxed; 1 = grimaced)
(d) body
movements (0 = relaxed; 1 = no gross movement; 2 = gross body movement)
(e)
state of arousal (0 = sleepy; 1 = awake; 2 = fussy)
(f) cry (0 = no; 1 =
whimper; 2 = vigorous) and combining the score
There was statistically
significant decrease in the composite score in the breastfeeding group compared
to swaddled group (MD -3; 95% CI -4, -2).
Comparison 2: Supplemental
breast milk vs. control
Six studies reported on this outcome (Blass 2001; Bucher 2000; Ors 1999; Skogsdal 1997; Upadhyay 2004 and Uyan 2005)
1. Physiological parameters
a. Outcome 02.01: Heart rate change (beats per minute)
Six studies reported on changes in the heart rate (Blass 2001; Bucher 2000; Ors 1999; Skogsdal 1997; Upadhyay 2004 and Uyan 2005). The heart
rate tended to increase in both groups during the procedure. There was no
statistically significant difference in the heart rate change between the
supplemental breast milk group and the placebo group (WMD -4; 95% CI -9 to 1
bpm; p = 0.08, I2 = 78%); supplemental breast milk and no treatment
group (MD -5; 95% CI -12 to 2 bpm; p = 0.17); supplemental breast milk and 10%
glucose group (MD 3; 95% CI -5 to 11 bpm; p = 0.50); supplemental breast milk
and artificial sweetener group (MD 8; 95% CI 0 to 16 bpm; p = 0.05) and
supplemental breast milk and glycine group (MD 4; 95% CI -3 to 11 bpm; p =
0.25). Statistical heterogeneity (Higgins 2003) was
identified when pooling data from breast milk vs. placebo studies (I2
= 78%; p = 0.0004) which is concordant with clinical heterogeneity
observed between studies (population and dose of breast milk). Blass 2001 reported on
mean heart rate change during and following the heel lance in the form of a bar
graph. The mean heart rate changes in the group given colostrum via a pacifier
and the groups given sucrose either via syringe or pacifier were significantly
less than the group given water, either by syringe or pacifier, and the group
given colostrum via syringe. Ors 1999 reported
significantly higher increase in the heart rate change in the supplemental
breast milk group compared to 25% sucrose group (MD 14; 95% CI 4 to 23). Skogsdal 1997
reported significantly higher increase in heart rate change in supplemental
breast milk group compared to 30% glucose group (MD 7, 95% CI 1, 13).
b. Changes in respiratory rate
None of the studies
included in this review reported on this outcome.
c. Outcome 02.02: Oxygen saturation change
One study reported on the change in oxygen saturation (Upadhyay 2004). The infants in the supplemental breast milk group compared to placebo group had no statistically significant difference in the change in oxygen saturation at three minutes (MD 0; 95% CI -2 to 2).
d. Changes in blood pressure
None of the studies included in this review reported on this outcome.
2. Cry variables
a. Outcome 02.03: Percentage of time crying
Blass 2001 reported the mean time spent crying during the recovery period in the form of a linear graph. This study identified a statistically significant reduction in the proportion time crying in the group given sucrose (via syringe or pacifier) compared to the control group and the group given colostrum (via syringe or pacifier) (p < 0.0015). There was no statistically significant difference between the colostrum group and the control group. It was not possible to abstract data from the graphs. Bucher 2000 reported statistically significant reduction in the percentage time crying in the artificial sweetener group compared to the supplemental breast milk group (MD 15; 95% CI 2 to 28), but no statistically significant reduction between the supplemental breast milk group and the placebo group (MD 9; 95% CI 2 to 20) and the supplemental breast milk group and the glycine group (MD 1; 95% CI -5 to 7).
b. Outcome 02.04: Duration of crying (in seconds)
Six studies (Blass 2001; Bucher 2000; Ors 1999; Skogsdal 1997; Upadhyay 2004 and Uyan 2005) reported on the duration of crying. Blass 2001 reported the reduction in crying time, however, the data was not in a format that could be abstracted. Upadhyay 2004 reported statistically significant reduction in the duration of crying among infants fed breast milk compared to placebo (71 secs; 95% CI 37 to 105 secs); comparative data could not be abstracted. Combining the data from four studies Bucher 2000; Ors 1999; Skogsdal 1997 and Uyan 2005 revealed no statistically significant difference in the duration of crying between the supplemental milk and the placebo group (WMD -6; 95% CI -16 to 3 secs). Ors 1999 observed statistically significant increase in the duration of crying in the supplemental breast milk group compared to the 25% glucose group (MD 33; 95% CI 12 to 54 secs). There was no statistically significant reduction in the duration of crying between the supplemental breast milk and the 30% glucose group (MD 13; 95% CI -3 to 29 secs); the supplemental breast milk group and the 10% glucose group (MD 4; 95% CI -15 to 23 secs) and the supplemental breast milk group and the artificial sweetener group (MD 41; 95% CI -7 to 89 secs). There was statistically significant reduction in the duration of crying in the glycine group compared to the supplemental breast milk group (MD 52; 95% CI 6 to 97 secs).
3. Validated pain measures
a. Neonatal infant pain score
None of the studies included in this review reported on this outcome.
b. Premature Infant Pain Profile
None of the studies included
in this review reported on this outcome.
c. Outcome 02.05: Neonatal Facial Coding Score at 3 minutes
Three studies (Bucher 2000; Upadhyay 2004; Uyan 2005) reported on NFCS. Bucher 2000 used five components of NFCS and Upadhyay 2004 modified the score and collected data on only part of the components. Bucher 2000 reported no statistically significant difference between the supplemental breast milk and the placebo group (MD -0.09; 95% CI -0.58, 0.40). Upadhyay 2004 reported statistically significant reduction in the NFCS in the supplemental breast milk group compared to the placebo group (MD -2.0; 95% CI -2.8 to -1.2). Uyan 2005 reported no statistically significant difference between the supplemental breast milk and the placebo group (MD -0.46; 95% CI -2.05, 1.13). There was marked heterogeneity in the data collection for NFCS. The data were not combined statistically due to this marked clinical heterogeneity. Bucher 2000 reported no statistically significant reduction in NFCS between supplemental breast milk group and artificial sweetener group (MD -0.2; 95% CI -0.7 to 0.2). However, a statistically significant reduction in NFCS was noted in the supplemental breast milk group compared to the glycine group (MD -0.47; 95% CI -0.90 to -0.04).
d. Other pain scores as reported (non validated)
i. Outcome 02.06: Body pain score
One study (Bucher 2000) reported on the body pain score outcome (maximum score was eight and minimum score was 0). There was no statistically significant reduction in body pain score between the supplemental breast milk and the placebo group (MD 0.5; 95% CI -0.4 to 1.3), the supplemental breast milk group and the artificial sweetener group (MD 0.2; 95% CI -0.7 to 1.0) and the supplemental breast milk group and the glycine group (MD 0.4; 95% CI -0.5 to 1.4).
Secondary outcome
Carbajal 2003 gathered information on infant's sucking behavior 48 to 72 hours after venepuncture by interviewing mothers. There was no difference in the number of infants in whom the suck was same or more effective among four groups (p = 0.14). The authors reported that infants who underwent venepuncture while they were being breast fed did not suck less effectively after the procedure.
Planned subgroup analyses according to gestational age groups was not performed in this version of the review because with the exception of one study (Skogsdal 1997), all other studies included only term infants. Other planned subgroup analyses according to type of intervention and type of procedure were not performed because subdividing the current data in these subgroup will have one and at the most two studies for comparison between groups at this point. However, in future updates of this review we plan to evaluate this subgroup analysis.
For preterm and sick full term neonates who are subjected to repeated painful procedures during hospitalization, the ideal analgesic has not yet been identified. Johnston 2002 evaluated effects of repeated administration of sucrose prior to painful procedures in infants < 31 weeks post-conceptional age. Use of sucrose was associated with reduced scores on motor development, vigour, alertness and orientation at 36 weeks; affected motor development and vigour at 40 weeks and higher Neuro-Biological Risk Score at two weeks postnatal age. Although unproven, breast milk may be an effective and safe alternative to sucrose even for repeated use. Placing small amount of solution in the oral cavity of small preterm infants was only associated with minor complication such as transient desaturation or transient choking which did not require any intervention. As breast milk is the most natural/physiological substance available for oral stimulation, repeated exposure is not perceived to be associated with complications of oral aversion or repeated tongue thrusting. However, this needs to be studied.
Several methodological challenges were apparent during this review. First, assessment of pain varied between studies. This has been a problem encountered in previous review of sucrose for procedural pain in neonates (Stevens 2004). Behavioural and physiological parameters of pain and/or validated pain measures were used to assess pain at random in various studies. Standardization of utilizing only validated pain scales should be the framework of further research. Future studies of adequate sample size should only include validated measures of pain as outcomes. Second, all studies explored effects of breastfeeding or breast milk following a single painful procedure. Future studies should include preterm or term neonates who require repeated painful stimuli to assess side effects of repeated oral administration of breast milk. Additionally, it should also measure the future success of breastfeeding as an outcome, as repeated conditioning may prime infant to refuse breastfeeding at a later stage. This is an important consideration particularly for preterm neonates. Only one study that evaluated maternal perception regarding sucking after single venepuncture while breastfeeding and found no changes; however, effect of repeated exposure is not studied. Thirdly, there was marked heterogeneity between studies in terms of control intervention, amount/time of prior exposure to breastfeeding or breast milk, time interval between this exposure and type of painful procedure.
Though the reasons for the effectiveness of breastfeeding over simple measures such as positioning/no intervention are unclear, it is perceived to be due to psychological and/or chemical properties of breast milk. On the other hand, the effectiveness of sucrose over breastfeeding is probably due to higher concentration of sugar in the former, however, the mechanism of action of sucrose is also unclear.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Blass 2001 | Quasi-randomized controlled trial I. Masking of randomization - can't tell II. Masking of intervention - no III. Masking of outcome assessment - no IV. Completeness of follow up - yes |
60 stable full term newborn infants undergoing routine newborn
screening (heel lance) between 30 and 55 hours of age were randomly
assigned to one of the 6 treatment groups (10 neonates in each group)
Mean (range) BW - 3200 (2400-4200) grams Male: Female - 27:33 |
Group 1: 2 ml water given over 2 minutes via syringe Group 2: 2 ml colostrum given over 2 minutes via syringe Group 3: 2 ml of 12% sucrose given over 2 minutes via syringe Group 4: 2 ml water given on a pacifier dipped in water every 30 seconds for 2 minutes Group 5: 2 ml of colostrum given on a pacifier dipped in colostrum every 30 seconds for 2 minutes Group 6: 2 ml of sucrose given on a pacifier dipped in sucrose every 30 seconds for 2 minutes |
Percentage of time crying during the procedure in relation to
control Percentage of time grimacing during the procedure Mean crying time during the recovery phase Mean changes in heart rate during and following the procedure |
C | |
| Bucher 2000 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - yes III. Masking of outcome assessment - yes IV. Completeness of follow up - yes |
80 stable full term newborn infants undergoing routine newborn
screening (heel lance) on postnatal day 3 were randomly assigned to one of
the 4 treatment groups Group 1: 20 neonates Mean (range) BW - 3420 (2650-5000) grams Male: Female - 10: 10 Group 2: 20 neonates Mean (range) BW - 3430 (2640-3960) grams Male: Female- 10:10 Group 3: 20 neonates Mean (range) BW - 3350 (2720-4200) grams Male: Female-8:12 Group 4: 20 neonates Mean (range) BW - 3410 (2740-4170) grams Male: Female-9:11 |
Group 1: 2 ml of artificial sweetener Group 2: 2 ml of glycine Group 3: 2 ml of breast milk Group 4: 2 ml of sterile water |
Heart rate change Percentage time crying Body pain score Facial pain score Combined pain score |
A | |
| Carbajal 2003 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - no III. Masking of outcome assessment - yes IV. Completeness of follow up - yes |
179 healthy term neonates Inclusion criteria: healthy term (>/= 37 weeks GA) undergoing venepuncture for diagnostic evaluation. Exclusion criteria: medical instability, received naloxone in the last 24 hours, received sedative or major analgesic in the last 48 hours. Group 1: 44 neonates Mean GA - 39.7 (1.15) weeks Mean BW - 3306 (382.8) grams Group 2: 45 neonates Mean GA - 39.8 (1.23) weeks Mean BW - 3304 (483.0) grams Group 3: 45 neonates Mean GA - 40.0 (1.14) weeks Mean BW - 3420 (418.8) grams Group 4: 45 neonates Mean GA - 39.6 (1.20) weeks Mean BW - 3313 (401.2) grams |
Group 1: Breastfeeding 2 minutes before and throughout the procedure
Group 2: Cuddled in mother's arms without breastfeeding starting 2 minutes prior to procedure Group 3: One ml of placebo (sterile water) without pacifier 2 minutes before the procedure while lying supine on the table Group 4: One ml of 30% glucose followed by pacifier 2 minutes prior to venepuncture while lying supine on the table |
Douleur Aigue Nouveau-ne (DAN) rating scale for pain in
neonates Premature Infant Pain Profile (PIPP) Standardized questionnaires to mothers to determine the effect of venepuncture on breastfeeding at 48-72 hours after the venepuncture |
A | |
| Gradin 2004 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - yes III. Masking of outcome assessment - yes IV. Completeness of follow up - no |
120 full term infants at 3-5 days of age undergoing venepuncture for
metabolic screening Exclusion criteria: feeding problems or suspicion of illness Group 1: 27 neonates Mean (range) GA - 39.4 (37-42) weeks Mean (range) BW - 3638 (2325-4425) grams Group 2: 29 neonates Mean (range) GA - 39.5 (37-42) weeks Mean (range) BW - 3637 (2700-4830) grams Group 3: 26 neonates Mean (range) GA - 39.4 (37-42) weeks Mean (range) BW - 3442 (2185-4560) grams Group 4: 29 neonates Mean (range) GA - 39.4 (37-42) weeks Mean (range) BW - 3660 (3025-4950) grams |
Group 1: Breastfeeding and 1 ml sterile water Group 2: Breastfeeding and 1 ml 30% glucose Group 3: Fasting and 1 ml sterile water Group 4: Fasting and 1 ml 30% glucose For breastfed group, breastfeeding was allowed for as long as the
infant wanted within 45 mins prior to blood sampling |
Premature Infant Pain Profile Visual Analogue Scale Median crying time |
A | |
| Gray 2002 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - no III. Masking of outcome assessment - no IV. Completeness of the follow up - yes |
30 term neonates Inclusion criteria: Healthy full term neonates delivered by normal spontaneous vaginal delivery undergoing heel lance for newborn screening Exclusion criteria: Patients with evidence of congenital abnormalities, medical complications, drug exposure, history of oxygen administration or ventilatory support Group 1: 15 neonates Mean GA - 39.8 weeks Mean BW - 3480 grams Group 2: 15 neonates Mean GA - 39.9 weeks Mean BW - 3524 grams |
Group 1: Breastfeeding during procedure Group 2: Swaddled in the bassinet during procedure |
Changes in facial grimacing, crying time and heart rate before, during and after blood collection | A | |
| Ors 1999 | Randomized controlled trial I. Masking of randomization - can't tell II. Masking of intervention - can't tell III. Masking of outcome assessment - yes IV. Completeness of the follow up - yes |
102 healthy term infants at median age of 1.6 days undergoing routine
heel lance blood sampling Exclusion criteria: Infants < 24 hours of age, Apgar score < 7 at 1 minute and on any medication were excluded Group 1: 35 neonates Median (range) GA - 40.0 (37-42) weeks Median (range) BW - 3220 (2445-4210) grams Group 2: 33 neonates Median (range) GA - 39.5 (37-42) weeks Median (range) BW - 3200 (2390-4200) grams Group 3: 34 neonates Median (range) GA - 39.0 (37-42) weeks Median (range) BW - 3380 (2450-4300) grams |
All infants were fed 1 hour before the procedure Group 1: 2 ml of 25 % sucrose Group 2: 2 ml of human milk Group 3: 2 ml of sterile water The solutions were administered by syringe over 1 minute Heel lance was performed 2 minutes after administration of the solution |
Recovery time Percentage change in heart rate at 1, 2 and 3 minutes Median crying time |
B | |
| Phillips 2005 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - no III. Masking of outcome assessment - not done for outcome recorded on video camera (cry duration, percentage time crying), outcomes on monitors (heart rate, saturation, blood pressure) were masked IV. Completeness of follow up - yes |
96 stable full term newborn infants undergoing routine newborn
screening (heel lance) were randomly assigned to one of the 3 treatment
groups Group 1: 32 neonates Mean (range) age at procedure - 37 (9) hours Male: Female - 13: 19 Group 2: 39 neonates Mean (range) age at procedure 36 (8) hours Male: Female- 13:26 Group 3: 25 neonates Mean (range) age at procedure 38 (14) hours Male: Female- 12:13 |
Group 1: Breastfeeding Group 2: Held by mother with use of pacifier Group 3: Held by research assistant with the use of pacifier |
Percentage of infants cried Proportion of cry time Heart rate, blood pressure and oxygen saturation change before and after the procedure |
A | |
| Shendurnikar 2005 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - no III. Masking of outcome assessment - no IV. Completeness of follow up - yes |
100 full term newborn infants who underwent heel lance were randomly
assigned to one of the 2 treatment groups Group 1: 50 neonates GA: 38.2 weeks Male: Female= 22:28 Group 2: 50 neonates GA: 38.6 weeks BW: 2865 grams Male: Female =31:19 Postnatal age 3.4 days BW: 2910 grams Postnatal age 3.1 days Inclusion criteria: Full term neonates >2500g BW Exclusion criteria: Septicemia, birth asphyxia, major congenital malformation |
Group 1: Breastfeeding group Group 2: Swaddled group |
Behavioral (state of arousal, cry, facial expression, body
movements) Physiological (heart rate, breathing pattern) Composite score |
A | |
| Skogsdal 1997 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - yes III. Masking of outcome assessment - yes IV. Completeness of follow up - yes |
120 stable newborn infants (66 preterm and 54 full term) undergoing
heel lance for blood collection for their care between 1 to 30 days of age
were randomly assigned to one of the 4 treatment groups (30 neonates in
each group) Exclusion criteria: age <24 hours, analgesic or sedative drug given within last 5 days, gestational age <30 weeks, ventilator or CPAP treatment, oxygen requirement > 40%, neurological symptoms, antibiotic therapy and age > 1 month Mean (SD) GA - 35.5 (2.3) weeks Mean (SD) age at testing - 5.4 (4.9) days |
Group 1: no treatment group Group 2: 1 ml of 30% glucose Group 3: 1 ml of 10% glucose Group 4: 1 ml of breast milk |
Crying time Heart rate change |
A | |
| Upadhyay 2004 | Randomized controlled trial I. Masking of randomization - yes II. Masking of intervention - yes III. Masking of outcome assessment - yes IV. Completeness of follow up - can't tell |
81 neonates requiring venepuncture for clinical
indication Inclusion criteria: GA of 37-41weeks who were </= 4 weeks of postnatal age and required venepuncture for clinical indication Exclusion criteria: Perinatal asphyxia (Apgar score < 7 at 1 min), major congenital malformations, admission to neonatal intensive care unit, maternal anesthesia, opiates administration before delivery or within 48 hours of sampling, babies given naloxone or phenobarbitone Group 1: 40 neonates Mean (SD) GA - 38 (0.9) weeks Mean (SD) BW - 2600 (300) grams Group 2: 41 neonates Mean (SD) GA - 38 (0.8) weeks Mean (SD) BW - 2900 (300) grams |
Group 1: 5 ml of expressed breast milk Group 2: 5 ml of distilled water The solutions were administered over 2 minutes prior to venepuncture |
Duration of crying after venepuncture Neonatal Facial Coding Score at 1 and 3 minutes after the venepuncture Changes in heart rate and oxygen saturation |
A | |
| Uyan 2005 | Quasi-randomized controlled trial I. Masking of randomization - no II. Masking of intervention - yes III. Masking of outcome assessment - yes IV. Completeness of the follow up - yes |
62 term infants undergoing heel lance blood sampling for screening
tests Exclusion criteria: preterm neonates, neonates with Apgar score < 7 at 5 minutes, neonates with low birth weight, sick neonates and neonates on any medication Group 1: 20 neonates Median (range) GA - 39 (38-41) weeks Median (range) BW - 3300 (2800-4260) grams Group 2: 21 neonates Median (range) GA - 39 (38-41) weeks Median (range) BW - 3510 (2750-4030) grams Group 3: 21 neonates Median (range) GA - 40 (38-41) weeks Median (range) BW - 3300 (2800-4500) grams |
All infants were fed 1 hour before the procedure Group 1: 2 ml of foremilk Group 2: 2 ml of hindmilk Group 3: 2 ml of sterile water The solutions were administered by syringe Heel lance was performed 2 minutes after administration of the solution |
Crying time Duration of first cry Percentage change in heart rate at 1, 2 and 3 minutes Neonatal Facial Coding Score |
C |
| Study | Reason for exclusion |
| Bilgen 2001 | Article is retracted by the journal. We have not used any of the data from this report because the data were previously reported by Ors 1999. |
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| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 Breastfeeding vs control | ||||
| 01 Heart rate change (beats per minute) | WMD (fixed), 95% CI | Subtotals only | ||
| 02 Oxygen saturation change | WMD (fixed), 95% CI | Subtotals only | ||
| 03 Blood pressure changes (mm of Hg) | WMD (fixed), 95% CI | Subtotals only | ||
| 04 Percentage of time crying | WMD (fixed), 95% CI | Subtotals only | ||
| 05 Duration of crying (secs) | WMD (fixed), 95% CI | Subtotals only | ||
| 06 Premature Infant Pain Profile Score | WMD (fixed), 95% CI | Subtotals only | ||
| 07 Douleur Aigue Nouveau-né (DAN) Scale | WMD (fixed), 95% CI | Subtotals only | ||
| 08 Composite score | 1 | 100 | WMD (fixed), 95% CI | -2.90 [-3.51, -2.29] |
| 02 Supplemental breast milk vs control | ||||
| 01 Heart rate change (beats per minute) | WMD (fixed), 95% CI | Subtotals only | ||
| 02 Oxygen saturation change | WMD (fixed), 95% CI | Subtotals only | ||
| 03 Percentage of time crying | WMD (fixed), 95% CI | Subtotals only | ||
| 04 Duration of crying (secs) | WMD (fixed), 95% CI | Subtotals only | ||
| 05 Neonatal Facial Coding Score at 3 minutes | WMD (fixed), 95% CI | No total | ||
| 06 Body pain score | WMD (fixed), 95% CI | Subtotals only | ||
01.01 Heart rate change (beats per minute)
01.01.01 Breastfeeding vs positioning
01.01.02 Breastfeeding vs pacifier use (neonate held by
mother)
01.01.03 Breastfeeding vs pacifier use (neonate held by research
assistant)
01.02 Oxygen saturation change
01.02.01 Breastfeeding vs pacifier use (neonate held by
mother)
01.02.02 Breastfeeding vs pacifier use (neonate held by research
assistant)
01.03 Blood pressure changes (mm of Hg)
01.03.01 Breastfeeding vs pacifier use (neonate held by
mother)
01.03.02 Breastfeeding vs pacifier use (neonate held by research
assistant)
01.04 Percentage of time crying
01.04.01 Breastfeeding vs positioning
01.04.02 Breastfeeding vs pacifier use (neonate held by
mother)
01.04.03 Breastfeeding vs pacifier use (neonate held by research
assistant)
01.05 Duration of crying (secs)
01.05.01 Breastfeeding vs no treatment
01.05.02 Breastfeeding vs sucrose/glucose
01.05.03 Breastfeeding vs positioning
01.06 Premature Infant Pain Profile Score
01.06.01 Breastfeeding vs placebo
01.06.02 Breastfeeding vs no treatment
01.06.03 Breastfeeding vs sucrose/glucose
01.06.04 Breastfeeding vs positioning
01.07 Douleur Aigue Nouveau-né (DAN) Scale
01.07.01 Breastfeeding vs placebo
01.07.02 Breastfeeding vs sucrose/glucose
01.07.03 Breastfeeding vs positioning
02 Supplemental breast milk vs control
02.01 Heart rate change (beats per minute)
02.01.01 Supplemental breast milk vs placebo
02.01.02 Supplemental breat milk vs no treatment
02.01.03 Supplemental breast milk vs 25% sucrose
02.01.04 Supplemental breas milk vs 30% glucose
02.01.05 Supplemental breast milk vs 10% glucose
02.01.06 Supplemental breast milk vs artificial sweetener
02.01.07 Supplemental breast milk vs Glycine
02.02 Oxygen saturation change
02.02.01 Supplemental breast milk vs placebo
02.03 Percentage of time crying
02.03.01 Supplemental breast milk vs placebo
02.03.02 Supplemental breast milk vs artificial sweetener
02.03.03 Supplemental breast milk vs glycine
02.04 Duration of crying (secs)
02.04.01 Supplemental breast milk vs placebo
02.04.02 Supplemental breast milk vs 25% sucrose
02.04.03 Supplemental breast milk vs 30% glucose
02.04.04 Supplemental breast milk vs 10% glucose
02.04.05 Supplemental breast milk vs artificial sweetener
02.04.06 Supplemental breast milk vs glycine
02.05 Neonatal Facial Coding Score at 3 minutes
02.05.01 Supplemental breast milk vs placebo
02.05.02 Supplemental breast milk vs artificial sweetener
02.05.03 Supplemental breast milk vs glycine
02.06.01 Supplemental breast milk vs placebo
02.06.02 Supplemental breast milk vs artificial sweetener
02.06.03 Supplemental breast milk vs glycine
Dr Vibhuti S Shah
Staff Neonatologist
Department of
Paediatrics
Mount Sinai Hospital
Room 775A
600 University
Avenue
Toronto
Ontario CANADA
M5G 1X5
Telephone 1: 416 586
4816
Telephone 2: 416 664 6708
Facsimile: 416 586 8745
E-mail: vshah@mtsinai.on.ca