Authors

  1. Benoit, Britney MSc(A)N, RN
  2. Martin-Misener, Ruth PhD, NP, RN
  3. Latimer, Margot PhD, RN
  4. Campbell-Yeo, Marsha PhD, NNP-BC, RN

Abstract

To provide an updated synthesis of the current state of the evidence for the effectiveness of breast-feeding and expressed breast milk feeding in reducing procedural pain in preterm and full-term born infants. A systematic search of key electronic databases (PubMed, CINAHL, EMBASE) was completed. Of the 1032 abstracts screened, 21 were found eligible for inclusion. Fifteen studies reported on the use of breast-feeding or expressed breast milk in full-term infants and 6 reported on preterm infants. Direct breast-feeding was more effective than maternal holding, maternal skin-to-skin contact, topical anesthetics, and music therapy, and was as or more effective than sweet tasting solutions in full-term infants. Expressed breast milk was not consistently found to reduce pain response in full-term or preterm infants. Studies generally had moderate to high risk of bias. There is sufficient evidence to recommend direct breast-feeding for procedural pain management in full-term infants. Based on current evidence, expressed breast milk alone should not be considered an adequate intervention.

 

Article Content

All infants undergo routine diagnostic and therapeutic painful procedures as part of universal medical care. While this exposure is highest in preterm and critically ill infants in the neonatal intensive care unit (averaging 12 painful procedures per day1,2), healthy full-term infants are also routinely exposed to painful procedures. For example, many infants will undergo a routine intramuscular injection of vitamin K to prevent bleeding3 and at least 1 heel lance to collect blood for metabolic testing4 and routine total serum bilirubin screening5 within the first days of age. Full-term infants who are at risk of hypoglycemia will further undergo repeated heel lancing for blood glucose testing on the basis of guidelines for infants at risk for low blood glucose.6 Furthermore, children undergo upward of 20 intramuscular injections for immunizations, with the majority occurring from 2 to 18 months of age.7

 

OUTCOMES OF UNTREATED PAIN IN INFANTS

In addition to causing unnecessary suffering to the smallest and most vulnerable of our population, unmanaged early pain exposure is associated with adverse neurological consequences. In research conducted with largely preterm infant samples, repeated pain exposure is associated with changes in somatosensory processing that continues into childhood, including changes in sensitivity and response to later pain.8-11 Pain exposure in preterm infants has additionally been associated with structural changes in the brain, including reduced maturation of white and subcortical gray matter at term equivalent age12 and reduced cortical thickness13 and cerebellum volume14 at school age in children born very preterm. The influence of untreated pain on the developing brain is further evidenced by research suggesting long-term motor, cognitive, and behavioral deficits. For example, exposure to pain in the neonatal period has been shown to be associated with poor body and head growth,15 reduced visual perceptual abilities at school age,16 poorer language outcomes at 18 months corrected age,17 greater internalizing behaviors throughout childhood,18,19 and altered development of the hypothalamic-pituitary-adrenal axis.20-23

 

While the majority of research examining the influence of untreated pain in infants has been conducted with those born preterm, the available evidence suggests that such exposure also produces adverse outcomes in full-term born infants. Studies examining the influence of early full-term infant exposure to major surgery,24-27 circumcision,28,29 burns,30 and repeated acute pain31-34 predominantly suggest that this exposure is associated with heightened pain responses to later painful stimuli.

 

BREASTFEEDING FOR THE TREATMENT OF INFANT ACUTE PAIN

In recognizing the adverse consequences of untreated pain in infants, national guidelines for evidence informed pain assessment and management practices have been developed.35,36 An intervention recommended in such guidelines for procedural pain management is breast-feeding. The most recent synthesis of the evidence of the use of breast-feeding or expressed breast milk as an analgesic intervention in infants was published in a Cochrane review in 2012. In this review, Shah and colleagues37 reported on 20 studies for a total sample of 2071 neonates who directly breastfed (10 studies, n = 1075) or received expressed breast milk (10 studies, n = 996) during acute needle-related painful procedures such as venipuncture, heel lance, and intramuscular injections. Of the 10 studies included in this systematic review examining direct breast-feeding,38-47 those examining its influence on physiological (eg, heart rate) and unidimensional behavioral (eg, cry time) measures of infant pain demonstrated consistent findings. Specifically, breastfed neonates demonstrated significantly lower heart rates,38,41,46 proportion crying time,38,41,44 duration of first cry,38,40,46-48 and total crying time44 than infants who were swaddled, held by their mothers, or received oral sucrose, a pacifier, placebo, or no intervention during the procedure.37

 

With respect to validated behavioral and biobehavioral infant pain measurement tools, Premature Infant Pain Profile (PIPP)49 scores were significantly lower in neonates who were breast-feeding during heel lance or venipuncture than in those who were positioned in their mothers' arms or received oral sucrose or a placebo.39,40,44 Similarly, Douleur Aigue du Nouveau-ne (DAN)50 scores were significantly lower in those neonates who were breast-feeding during painful procedures than in those neonates who were held in their mothers' arms or received a placebo.39 However, there was no significant difference in DAN scores between breast-feeding neonates and those receiving oral glucose.39 Similarly, while Neonatal Infant Pain Scale (NIPS)51 scores were lower for breast-feeding neonates than for those with no intervention, there was no significant statistical difference in NIPS scores between breast-feeding neonates and those who received oral sucrose.48 Finally, while Neonatal Facial Coding System52 scores were lower in the breast-feeding group than those in oral glucose, pacifier use, maternal holding, or no intervention, breast-feeding was not statistically significantly more effective than provision of formula.45,46 A moderate level of evidence quality based on the GRADE (ie, Grading of Recommendations Assessment, Development, and Evaluation)53 criteria was reported for all of the studies examining the influence of direct breast-feeding.37

 

In comparison to direct breast-feeding, there was considerable variability across the 10 studies examining provision of expressed breast milk for pain relief.37 Expressed breast milk reduced duration of crying when compared to placebo,54-60 and behavioral pain response measured using the NFCS when compared to placebo in one61 of three studies reporting on this outcome. However, oral sucrose in 12.5%, 20%, and 25% concentrations; oral glucose in 25% and 30% concentrations; and pacifier use, rocking, and no intervention were more effective than breast milk in reducing duration of crying55,59,60,62 and heart rate.54,55,57,63 Furthermore, expressed breast milk was not effective in reducing NIPS62 and DAN scores.59 Taken together, the authors of this review reported that direct breast-feeding is clearly superior when compared with the provision of expressed breast milk for procedural pain relief.

 

Despite this evidence, the routine use of breast-feeding to reduce needle-related pain in healthy infants remains underutilized in practice.64 The limited reported use of breast-feeding to reduce acute pain in newborns may be related to outstanding clinical research questions. However, since the publication of the most recent Cochrane review and meta-analysis of the breast-feeding literature, there has been substantial research activity on this topic. Specifically, the majority of studies included in this Cochrane review reported on only healthy full-term born infants, with only 1 of the 20 studies including stable late preterm infants in addition to full-term infants in their sample.54 There are now several studies reporting on the influence of expressed breast milk and direct breast-feeding for pain reduction in strictly preterm infant samples. Furthermore, there are additional available studies including samples of full-term infants. A synthesis of this evidence makes a valuable contribution to the literature to inform timely updates to clinical practice guidelines and future research in this area.

 

AIMS

The purpose of this systematic review of the literature is to provide an updated synthesis of the current state of the evidence for the influence of breast-feeding and expressed breast milk feeding on acute procedural pain in preterm and full-term born infants.

 

METHODS

To address the aims of this article, a systematic review methodology was utilized. Standards for the conduct of systematic reviews have been outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) group65 and include standards for clearly reporting the rationale of the paper, eligibility criteria, sources of information, search terms and delimiting, and synthesis of the evidence. These guidelines were followed in the completion of this systematic review.65

 

Literature search

Key electronic databases (PubMed, CINAHL, EMBASE) were searched from 2011 (as this was the date to which the most recent Cochrane review search strategy was completed) through to December 22, 2016. The systematic search strategy, which was developed in collaboration with a health sciences librarian specializing in systematic searches, included key terms for infants, pain exposure, and breast-feeding. Medical Subject Headings (MeSH) terms and other key terms were included where possible in each database.

 

Eligibility criteria

Eligibility criteria required that included studies (1) be an empirical investigation (ie, an experimental or quasi-experimental quantitative study) examining the use of breastfeeding or expressed breast milk as a pain relieving intervention, (2) include a sample of full-term or preterm born infants, and (3) be published in English in a peer-reviewed journal. Pain exposure was defined as acute procedural pain (eg, heel lancing, intramuscular injections, venipuncture). Studies that quantified physiological (eg, heart rate, oxygen saturation), behavioral (eg, facial actions, cry duration), brain-based (eg, pain-specific response using neurophysiological measures), and hormonal (eg, changes in cortisol patterns) pain responses were all considered eligible for inclusion.

 

Study selection and data extraction

The titles and abstracts of all of the articles generated by the systematic search were reviewed by the first author (B.B.), and full texts of articles deemed to be relevant were reviewed by the first author (B.B.) and study coinvestigator (M.C.Y.) to verify eligibility for inclusion. Of those studies meeting inclusion criteria, full texts of the articles were reviewed and data on study purpose, sample characteristics, and all outcomes were extracted. Figure 1 outlines the PRISMA flow diagram for identification and screening of studies in this review. Risk of bias for each included study was rated by the first author (B.B.) using the Cochrane Risk of Bias Assessment Tool for Randomized Studies of Interventions66 or the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tools67 as appropriate. Specifically, the first author scored each study as low, high, or unclear risk of bias across each of the 7 domains included in the Cochrane risk of bias tools and drew conclusions regarding the overall risk of bias score for each study by judiciously considering the rating and contribution of each domain.68

  
Figure 1 - Click to enlarge in new windowFigure 1. PRISMA flow diagram for the process of identification and screening of articles for inclusion in a systematic review and meta-analysis. From Moher et al.

RESULTS

The number of studies reporting on the use of direct breast-feeding for acute pain management in full-term infants has more than doubled, with an additional 15 studies (n = 1908 infants) being published (see Table 1). Furthermore, 6 studies (n = 428) have been published examining the use of breast-feeding and expressed breast milk feeding for procedural pain management in preterm infants, which have not been previously synthesized in the literature.

  
Table 1 - Click to enlarge in new windowTable 1. Summary and risk of bias of included studies reporting on the use of breast-feeding or expressed breast milk as an analgesic intervention in full-term newborns undergoing acute procedures

Evidence for breast-feeding and expressed breast milk in full-term infants

All of the additional studies comparing direct breast-feeding to alternate interventions in full-term infants report consistent and positive analgesic effects. Two additional studies compare direct breast-feeding with topical anesthetics,69,70 3 compare breast-feeding with sweet taste interventions (oral sweet solutions such as glucose or sucrose placed on to the anterior tip of the infant's tongue),71,72,73 and 2 compare breast-feeding with skin-to-skin contact (SSC).74,75 Three new studies compare breast-feeding with simple holding,76-78 1 with music therapy,79 and 1 with nonnutritive sucking.80 Finally, 3 studies have reported on the use of expressed breast milk compared with sweet taste interventions.81-83 These studies generally had moderate to high risk of bias (see Table 1). As the findings of these studies have not previously been synthesized, the following section of this review will report on their results.

 

Breast-feeding versus music therapy

A single randomized controlled trial of 288 healthy full-term neonates compared the influence of music therapy, breast-feeding, or the combination of these interventions on NIPS scores, cry duration, and latency to cry, following a heel lance.79 The authors reported that infants who were breast-feeding, both with or without music, demonstrated significantly lower NIPS scores than those who received music therapy alone.79 Furthermore, infants who were breast-feeding had significantly longer latency to first cry and shorter duration of first cry than those receiving music therapy. Thus, the findings of this study suggest that when compared with breast-feeding, music therapy is an ineffective intervention for the reduction of procedural pain in full-term neonates.

 

Breast-feeding versus topical anesthetics and cooling sprays

One study reported on the comparison of breast-feeding with topical anesthetics and 1 reported on the use of a cooling spray. In a sample of full-term born infants undergoing intramuscular injection for immunization, those who were breast-feeding during the procedure demonstrated a significantly higher frequency of painless injections as measured using the NIPS than those infants who received a vapocoolant spray at the site of injection or no intervention.69 A similar finding was demonstrated by Gupta and colleagues,70 who assigned healthy full-term infants to receive (1) EMLA (Eutectic Mixture of Local Anesthetics) plus breast-feeding, (2) EMLA plus water, or (3) placebo cream plus water before immunization. Those infants who received the combined intervention of EMLA and breast-feeding demonstrated significantly lower Modified Facial Coding System scores and shorter duration of cry than those infants receiving EMLA alone or placebo, suggesting synergistic effects of breast-feeding and topical anesthetics during immunization.70

 

Breast-feeding versus sweet taste interventions

Three studies compared the analgesic efficacy of breast-feeding and sweet taste interventions and demonstrated findings consistent with those previously synthesized in the literature. For example, duration of cry, latency of cry, and Modified Facial Coding System scores were consistent between those infants who were breastfed during intramuscular injection and those who received 25% dextrose solution.72 However, both of these interventions (ie, breast-feeding or receiving 25% dextrose 2 minutes prior to injection) were found to significantly reduce duration of cry and latency of onset of cry compared with placebo.72 In a trial of 100 full-term newborns randomly assigned to receive 30% glucose or breastfeed during heel lance, NIPS was significantly lower in the breastfed group.73 Furthermore, a randomized controlled trial including 30 healthy full-term neonates demonstrated that NIPS was significantly reduced in those infants who were breastfed before heel lance compared with those receiving 20% oral glucose prior to procedure.84 In this trial, brain-based response measured using near infrared spectroscopy was reported in addition to the NIPS score. Infants who were breast-feeding during the procedure demonstrated significant increases in oxygenated hemoglobin over the left superior sensorimotor cortex, left somatosensory cortex, right superior sensorimotor cortex, right posterior-superior frontal cortex, and the right posterior parietal cortex.84 Increases in oxygenated hemoglobin measured using near infrared spectroscopy may reflect an increase in neuronal activation secondary to the painful stimulus.85 However, as activation of these brain regions would be anticipated during breast-feeding due to the sensory and motor stimulation associated with close maternal contact and oral movements, the influence of breast-feeding on pain-specific activity isolated from the confounding activity in this intervention group is difficult to discern. Thus, consistent with the finding synthesized by Shah and colleagues,37 the current evidence would suggest that the analgesic effect of breast-feeding is equally as effective, if not more effective, than sweet taste interventions for full-term infants undergoing acute procedures.

 

Breast-feeding versus simple holding and direct skin-to-skin contact

Three studies comparing breast-feeding with being held without SSC during painful procedures all demonstrated that breast-feeding is significantly more analgesic.76-78 Pain associated with intramuscular injection measured using the DAN76 and the NIPS78 was found to be significantly lower when infants were actively breast-feeding 2 minutes prior to and during immunization when compared with simply being held in their mothers' lap during the procedure. Furthermore, in a sample of 128 healthy full-term neonates undergoing a heel lance for routine metabolic screening, breast-feeding was found to significantly reduce PIPP scores compared with maternal holding.77

 

In the 2 studies that compared breast-feeding with direct maternal-infant SSC, breast-feeding continues to appear superior for pain management in full-term neonates. Marin Gabriel and colleagues75 first compared these interventions in a randomized controlled trial of 136 healthy full-term neonates who were randomly assigned to 1 of 4 intervention conditions: (1) maternal SSC and breast-feeding, (2) maternal SSC and 24% oral sucrose, (3) 24% oral sucrose alone, or (4) maternal SSC alone. Median NIPS scores and the percentage of time that the neonates were scored as having moderate to severe pain were significantly lower in the maternal SSC and breast-feeding group than in the other groups. Furthermore, both the maternal SSC and breast-feeding and maternal SSC and sucrose groups demonstrated a significantly lower percentage of crying than the SSC alone group,75 suggesting a potential additive effect of combining these interventions. Breast-Feeding was further demonstrated to be significantly more effective in reducing pain response measured using NIPS and cry duration than maternal SSC or swaddling prior to immunization in healthy full-term infants.74 While it is unclear whether infants were held in SSC during breast-feeding in this study,74 it is likely that the combination of maternal SSC and breast-feeding provides the greatest analgesic benefit.

 

Breast-feeding versus nonnutritive sucking

Only 1 study was identified that compared direct breast-feeding with nonnutritive sucking in full-term healthy newborns.80 This study, which was described as a case-control study but reported randomized controlled trial methodology, found that those infants who were breast-feeding during the procedure and those who received nonnutritive sucking both had lower NIPS scores that those infants who did not receive any analgesia during venipuncture. However, there was no statistically significant difference in NIPS scores between the breast-feeding and nonnutritive sucking groups.80

 

Expressed breast milk versus sweet taste interventions

Three studies were included that reported on the comparative analgesic efficacy of expressed breast milk and sweet taste interventions in full-term infants. Expressed breast milk has been found to be more effective than no intervention in reducing DAN score and crying time during venipuncture.83 One study comparing expressed breast milk and 24% oral glucose demonstrated that those infants who received breast milk had significantly lower heart rates and higher oxygen saturation following heel lance.81 In contrast, Sahoo and colleagues82 compared expressed breast milk, 25% dextrose, and sterile water for pain relief during venipuncture and found that while expressed breast milk was more effective in reducing PIPP scores, heart rate, and cry duration than sterile water, it was not more effective than 25% dextrose.82

 

Evidence for breast-feeding and expressed breast milk in preterm infants

Of the 6 studies (n = 428; see Table 2) identified by this systematic review reporting on direct breast-feeding and expressed breast milk feeding for pain management in preterm infants, there is limited evidence for its analgesic efficacy. Provision of expressed breast milk was not as effective as sweet taste in premature neonates ranging from 32 to 36 completed weeks' gestational age at birth,54,86-88 and no difference was found between expressed breast milk and maternal-infant SSC during tape removal in very low-birth-weight neonates with an average gestational age at enrollment of approximately 32 weeks.89 One study examining direct breast-feeding in preterm infants, which randomly assigned 57 infants born between 30 and 36 weeks' gestational age to receive either direct breast-feeding or nonnutritive sucking during heel lance (performed, on average, at day 9 of age), reported no significant difference in Behavioral Indicators of Infant Pain score or heart rate between the 2 groups.90 However, although no overall group effect of breast-feeding was found, preterm breast-feeding infants in this study who had more mature breast-feeding behaviors as assessed using the Premature Infant Breast-Feeding Behaviors Scale demonstrated lower pain responses during the heel lance, heel squeeze, and recovery phases of data collection.90 One study examining the analgesic effect of expressed breast milk combined with standard care (topical anesthetic drops applied to the eye, swaddling, and nesting) for retinopathy of prematurity examinations in neonates born at less than 35 weeks' gestational age found that the addition of breast milk significantly reduced pain scores when compared with standard care alone.91 These studies generally had low risk of bias (see Table 2).

  
Table 2 - Click to enlarge in new windowTable 2. Summary and risk of bias of included studies reporting on the use of breast-feeding as an analgesic intervention in preterm newborns undergoing acute procedures

DISCUSSION

As is evidenced from this systematic review of the literature, the number of studies reporting on the use of direct breast-feeding and the provision of expressed breast milk as an analgesic intervention in infants has more than doubled in the last 4 years. While the majority of these studies have reported on the use of this intervention in full-term infants, there is an emerging body of evidence using breast-feeding and expressed breast milk for pain in preterm infants.

 

The findings of this review are consistent with the previously synthesized literature in that direct breast-feeding appears to be superior in comparison to the use of expressed breast milk. The additional studies included in this review utilizing expressed breast milk compared with sweet taste in preterm infants found that the provision of expressed breast milk was no more effective than sweet taste (ie, 25% glucose or 24% sucrose) in reducing pain from heel lancing as measured by composite biobehavioral pain score (ie, PIPP) or cry indicators such as duration of cry after procedure.54,86-88 Of the 3 additional published records reporting on the use of expressed breast milk in full-term newborns, only 1 reported a significant effect of expressed breast milk compared with sweet taste on select physiologic pain indicators.81 This limited effect of expressed breast milk is not surprising given current hypotheses regarding the mechanisms of effectiveness of expressed breast milk and sweet-tasting interventions. While the exact mechanisms of these interventions are not yet fully elucidated, research demonstrating that the effects of sucrose occurred rapidly, are short lasting, and are blocked by systemic opioid receptor antagonists suggest that the effects are mediated by endogenous opioid release.92-95 Sweeter and more concentrated solutions (eg, 24% oral sucrose; 20%-30% glucose96) have demonstrated more robust pain-reducing effects than solutions with lower concentrations of sweet taste.97,98 Given that breast milk contains only 7% lactose, provision of breast milk alone does not appear to be an effective pain-relieving intervention and thus, direct breast-feeding is likely necessary to gain optimal analgesic efficacy.

 

Direct breast-feeding is a multisensorial intervention that encompasses a combination of individually pain-reducing interventions such as maternal closeness and SSC,99 olfactory,100,101 and oral102 stimulation. Thus, it is not surprising that in contrast to studies examining the provision of expressed breast milk, the newly synthesized studies examining direct breast-feeding consistently found it to be an effective analgesic intervention in full-term infants. Consistent with the studies reported in the most recent Cochrane review,37 breast-feeding demonstrated superior analgesic efficacy in all studies comparing it with simple maternal holding.76-78 Interestingly, the use of breast-feeding in combination with alternate interventions, such as EMLA70 and SSC,75 appears to be more effective in reducing behavioral responses to pain than using these interventions alone in full-term infants. This suggests the potential benefit of using breast-feeding in combination with adjuvant therapies to provide optimal pain relief.

 

While the available evidence suggests that breast-feeding is more effective in reducing pain than simple holding, topical anesthetics, and SSC alone during acute procedures, the additional studies included in this systematic review continue to report inconsistent outcomes when comparing direct breast-feeding and sweet tasting interventions. For example, while breast-feeding infants were found to have significantly lower NIPS scores than those receiving 20% glucose84 in 1 study, pain response measured as facial actions and cry indicators were statistically similar between breast-feeding infants and those receiving 25% dextrose in another.72 While it could be hypothesized that these findings are related to the concentration of sweet solutions utilized in these studies, future research is needed to examine the relationship between these interventions. However, unlike the administration of sucrose during pain, which has reported potential adverse effects following repeated dosing such as poorer attention and motor development in preterm infants born less than 31 weeks,103,104 no studies to date have reported on adverse effects associated with breast-feeding during painful procedures.37,75 While additional research examining the potential for adverse outcomes associated with sweet-tasting solutions for pain in full-term infants is needed, there is no evidence for adverse infant outcomes associated with breast-feeding. With the exception of the rare risk of transmitting microorganisms from mother to infant,37 breast-feeding has been associated only with optimizing infant and maternal outcomes, including improved immunological function,105 improved developmental outcomes,106 reduction in obesity risk107,108 and reduced risk of diabetes,107,109,110 celiac disease,111 and inflammatory bowel disease112 in infants, as well as reduced risk of breast and ovarian cancers113 in mothers.

 

Recommendations for clinical practice

Given that direct breast-feeding has demonstrated efficacy that is equal to, or greater than, sweet taste interventions in reducing behavioral and physiological responses to pain in full-term infants undergoing heel lance, intramuscular injection, and venipuncture (in addition to numerous additional health outcomes in a nonpain context and no demonstrated adverse outcomes), direct breast-feeding should be considered the preferred first-line analgesic intervention for painful procedures performed on full-term infants. Therefore, targeted education and supports should be directed toward both clinicians and parents to facilitate the utilization of direct breast-feeding as an analgesic intervention for full-term infants during painful procedures.

 

In contrast, there is limited evidence to support that expressed breast milk should be used as a sole analgesic intervention in full-term infants undergoing painful procedures. For preterm infants who do not have demonstrated maturity to feed directly at the breast, provision of expressed breast milk for pain reduction should not be utilized as the sole pain-relieving intervention, given the limited evidence for its efficacy. Rather, use of maternal infant skin-to-skin99 contact and/or 24% oral sucrose95 that have demonstrated efficacy in the preterm population should be utilized.

 

Recommendations for future research

While the majority of studies comparing these interventions reported that breast-feeding was significantly more analgesic than sweet taste,73,84,114 these studies predominantly had high risk of bias. In one study with a low risk of bias, breast-feeding and higher concentrations of sweet-tasting solutions (eg, 25% dextrose72) demonstrated similar efficacy in reducing behavioral responses to pain. Furthermore, studies reporting on the ability of these interventions to reduce pain response in the infant brain-and thus act as true analgesic interventions-are limited. One study reporting on the use of 24% sucrose to reduce pain-specific event-related potentials in the neonate brain demonstrated that while sucrose significantly reduced biobehavioral pain response measured using the PIPP, its effects in the brain did not differ from placebo.115 This would suggest that the effects of sucrose may be sedative in nature, rather than analgesic-a hypothesis that is supported by the limited ability of sucrose to prevent hyperalgesia from developing in infants who are exposed to repeated acute procedures in early life in one study.33 Given the multimodal nature of breast-feeding analgesia, it is reasonable to hypothesize that breast-feeding may demonstrate superior effects to sweet taste in reducing pain response in the infant brain. However, while one study has examined the influence of breast-feeding on a brain-based measure (i.e., near infrared spectroscopy) during a painful procedure,71 the activation demonstrated could not be isolated as pain specific. Therefore, rigorous randomized controlled trials examining the influence of breast-feeding on sensitive and specific brain-based indicators of pain, in addition to behavioral pain indicators, are needed.

 

Only 1 study in this review reported on the use of direct breast-feeding for pain relief in preterm infants and found no effect.90 However, the findings of this study suggested that breast-feeding maturity (such as longer sucking bursts and more active rooting reflexes) may contribute to the analgesic efficacy of breast-feeding and should be considered when determining whether direct breast-feeding is an appropriate intervention for preterm infants undergoing painful procedures. Future research aimed at identifying at what point breast-feeding maturity is sufficient to offer analgesia to preterm infants is thus warranted. Furthermore, while studies reporting on the use of expressed breast milk demonstrate limited efficacy, future research to determine whether there is a dose-dependent effect of expressed breast milk as well as the potential benefit of using expressed breast milk as an adjuvant intervention (eg, combined with SSC) in preterm infants is needed to inform its use in research and clinical practice.

 

Strengths and limitations

A strength of the present systematic review is that it followed the acceptable standards for the completion and reporting of a systematic review of the literature.65 A limitation of this work is that, because of resource constraints, only 1 reviewer (B.B.) completed risk of bias scoring and level 1 and 2 screening for eligible studies, with the final sample of included studies being verified by a study coinvestigator (M.C.Y.). Although unlikely given the explicit inclusion criteria, not employing 2 independent reviewers in the screening process may have reduced the number of eligible studies that were identified for inclusion.116

 

CONCLUSION

The use of breast-feeding and expressed breast milk for pain relief in infants undergoing acute procedures is increasingly being examined in the literature. While there is limited evidence to support the use of these interventions in preterm infants, the available literature supports that breast-feeding is as or more effective than sweet-tasting solutions such as 24% oral sucrose. Future research examining the influence of breast-feeding on brain-based indicators of pain, as well as the influence of breast-feeding maturity and expressed breast milk dose on pain-reducing effects in preterm infants, is needed to support understanding of the mechanisms of efficacy and recommendations regarding utilization in clinical care. However, based on the evidence supporting the benefits of direct breast-feeding in both pain and nonpain contexts, it should currently be supported as a first-line intervention in full-term infants undergoing heel lance, venipuncture, and intramuscular injections.

 

References

 

1. Johnston C, Barrington KJ, Taddio A, Carbajal R, Filion F. Pain in Canadian NICUs: have we improved over the past 12 years? Clin J Pain. 2011;27(3):225-232. doi:10.1097/AJP.0b013e3181fe14cf; 10.1097/AJP.0b013e3181fe14cf. [Context Link]

 

2. Carbajal R, Danan C, Coquery S, et al Epidemiology and treatment of painful procedures in neonates in intensive care units. 2008;300(1):60-70. [Context Link]

 

3. McMillan D, Canadian Paediatric Society Fetus and Newborn Committee. Routine administration of vitamin K. Paediatr Child Heal. 2016;2(6):429-431. [Context Link]

 

4. Maritime Newborn Screening Service. Maritime Newborn Screening Program PL-0166. http://http://www.iwk.nshealth.ca/resources#/content/maritime-newborn-screening-program-pl-0166. Published 2014. Accessed June 20, 2016. [Context Link]

 

5. Barrington KJ, Sankaran K, Society CP. Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm. Paediatr Child Heal. 2016;12(suppl B):1B-12B. [Context Link]

 

6. Aziz K, Dancey P, Canadian Paediatric Society Fetus and Newborn Committee. Screening guidelines for newborns at risk for low blood glucose. Can Paediatr Soc Position Statement. 2016;9(10):723-729. [Context Link]

 

7. Public Health Agency of Canada. Canadian immunization guide. http://http://www.phac-aspc.gc.ca/publicat/cig-gci/p01-12-eng.php#tab1. Published 2013. Accessed June 20, 2016. [Context Link]

 

8. Grunau RE, Holsti L, Haley DW, et al Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU. Pain. 2005;113(3):293-300. doi:S0304-3959(04)00528-7 [pii]. [Context Link]

 

9. Grunau RE, Oberlander TF, Whitfield MF, Fitzgerald C, Morison SJ, Philip Saul J. Pain reactivity in former extremely low birth weight infants at corrected age 8 months compared with term born controls. Infant Behav Dev. 2001;24(1):41-55. doi:10.1016/S0163-6383(01)00065-0. [Context Link]

 

10. Johnston CC, Stevens BJ. Experience in a neonatal intensive care unit affects pain response. Pediatrics. 1996;98(5):925-930. [Context Link]

 

11. Hermann C, Hohmeister J, Demirakca S, Zohsel K, Flor H. Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain. 2006;125(3):278-285. doi:S0304-3959(06)00452-0 [pii]. [Context Link]

 

12. Brummelte S, Grunau RE, Chau V, et al Procedural pain and brain development in premature newborns. Ann Neurol. 2012;71(3):385-396. doi:10.1002/ana.22267. [Context Link]

 

13. Ranger M, Chau CM, Garg A, et al Neonatal pain-related stress predicts cortical thickness at age 7 years in children born very preterm. PLoS One. 2013;8(10):e76702. doi:10.1371/journal.pone.0076702. [Context Link]

 

14. Ranger M, Zwicker JG, Chau CMY, et al Neonatal pain and infection relate to smaller cerebellum in very preterm children at school age. J Pediatr. 2015;167(2):292-298.e1. doi:10.1016/j.jpeds.2015.04.055. [Context Link]

 

15. Vinall J, Miller SP, Chau V, Brummelte S, Synnes AR, Grunau RE. Neonatal pain in relation to postnatal growth in infants born very preterm. Pain. 2012;153(7):1374-1381. doi:10.1016/j.pain.2012.02.007. [Context Link]

 

16. Doesburg SM, Chau CM, Cheung TP, et al Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age. Pain. 2013;154(10):1946-1952. doi:10.1016/j.pain.2013.04.009. [Context Link]

 

17. Vinall J, Grunau RE, Zwicker JG, et al Early neonatal pain exposure and brain microstructure interact to predict neurodevelopmental outcomes at 18 months corrected age in children born very preterm. Int J Deve. 2015;47(Part A):47. doi:10.1016/j.ijdevneu.2015.04.132. [Context Link]

 

18. Ranger M, Synnes AR, Vinall J, Grunau RE. Internalizing behaviours in school-age children born very preterm are predicted by neonatal pain and morphine exposure. Eur J Pain. 2014;18(6):844-852. doi:10.1002/j.1532-2149.2013.00431.x. [Context Link]

 

19. Vinall J, Miller SP, Synnes AR, Grunau R. Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely. Pain. 2013;154(9):1831-1839. doi:10.1016/j.pain.2013.05.050. [Context Link]

 

20. Brummelte S, Chau CMY, Cepeda IL, et al Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress. Psychoneur-oendocrinology. 2015;51:151-163. doi:10.1016/j.psyneuen.2014.09.018. [Context Link]

 

21. Grunau RE, Tu MT, Whitfield MF, et al Cortisol, behavior, and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm. Clin J Pain. 2010;26(8):698-704. doi:10.1097/AJP.0b013e3181e5bb00. [Context Link]

 

22. Grunau RE, Haley DW, Whitfield MF, Weinberg J, Yu W, Thiessen P. Altered basal cortisol levels at 3, 6, 8 and 18 months in infants born at extremely low gestational age. J Pediatr. 2007;150(2):151-156. doi:S0022-3476(06)01027-4 [pii]. [Context Link]

 

23. Grunau RE, Weinberg J, Whitfield MF. Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months. Pediatrics. 2004;114(1):e77-e84. http://ezproxy.library.dal.ca/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=c8h&AN=2005078043&site=ehost-live NS-. [Context Link]

 

24. Andrews K, Fitzgerald M. Wound sensitivity as a measure of analgesic effects following surgery in human neonates and infants. Pain. 2002;99(1-2):185-195. doi:10.1016/S0304-3959(02)00100-8. [Context Link]

 

25. Peters JW, Koot HM, de Boer JB, et al Major surgery within the first 3 months of life and subsequent biobehavioral pain responses to immunization at later age: a case comparison study. Pediatrics. 2003;111(1):129-135. [Context Link]

 

26. Peters JWB, Schouw R, Anand KJS, van Dijk M, Duivenvoorden HJ, Tibboel D. Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain. 2005;114(3):444-454. doi:10.1016/j.pain.2005.01.014. [Context Link]

 

27. Schmelzle-Lubiecki BM, Campbell KA, Howard RH, Franck L, Fitzgerald M. Long-term consequences of early infant injury and trauma upon somatosensory processing. Eur J Pain. 2007;11(7):799-809. doi:10.1016/j.ejpain.2006.12.009. [Context Link]

 

28. Taddio A, Goldbach M, Ipp M, Stevens B, Koren G. Effect of neonatal circumcision on pain responses during vaccination in boys. Lancet. 1995;345(8945):291-292. doi:S0140-6736(95)90278-3 [pii]. [Context Link]

 

29. Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349(9052):599-603. doi:S0140-6736(96)10316-0 [pii]. [Context Link]

 

30. Wollgarten-Hadamek I, Hohmeister J, Demirakca S, Zohsel K, Flor H, Hermann C. Do burn injuries during infancy affect pain and sensory sensitivity in later childhood? Pain. 2009;141(1-2):165-172. doi:10.1016/j.pain.2008.11.008. [Context Link]

 

31. Ozawa M, Kanda K, Hirata M, Kusakawa I, Suzuki C. Influence of repeated painful procedures on prefrontal cortical pain responses in newborns. Acta Paediatr Int J Paediatr. 2011;100(2):198-203. doi:10.1111/j.1651-2227.2010.02022.x. [Context Link]

 

32. Piira T, Champion GD, Bustos T, Donnelly N, Lui K. Factors associated with infant pain response following an immunization injection. Early Hum Dev. 2007;83(5):319-326. doi:S0378-3782(06)00185-X [pii]. [Context Link]

 

33. Taddio A, Shah V, Atenafu E, Katz J. Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants. Pain. 2009;144(1-2):43-48. doi:10.1016/j.pain.2009.02.012. [Context Link]

 

34. Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. JAMA. 2002;288(7):857-861. doi:joc12153 [pii]. [Context Link]

 

35. American Academy of Pediatrics Committee on Fetus and Newborn and Section on Anesthesiology and Pain Medicine. Prevention and management of procedural pain in the neonate: an update. Pediatrics. 2016;137(2):1-13. doi:10.1542/peds.2015-4271. [Context Link]

 

36. Batton DG, Barrington KJ, Wallman C. Prevention and management of pain in the neonate: an update. Policy statement [corrected] [published erratum appears in PEDIATRICS February 2007;119(2):425]. Pediatrics. 2006;118(5):2231-2241. http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=2009337795&site=ehost-live. [Context Link]

 

37. Shah PS, Herbozo C, Aliwalas LL, et al Breastfeeding or breast milk for procedural pain in neonates. Cochrane Databased of Systematic Reviews. 12: CD009450. doi:10.1002/14651858 .CD004950.pub3. [Context Link]

 

38. Gray L, Miller LW, Philipp P, Blass EM. Breast-Feeding is analgesic in healthy newborns. Pediatrics. 2002;18(4):590-593. doi:10.1177/08934402018003015. [Context Link]

 

39. Carbajal R, Veerapen S, Couderc S, Jugie M, Ville Y. Analgesic effect of breast-feeding in term neonates: randomised controlled trial. BMJ. 2003;326(7379):13. [Context Link]

 

40. Gradin M, Finnstrom O, Schollin J. Feeding and oral glucose-additive effects on pain reduction in newborns. Early Hum Dev. 2004;77(1-2):57-65. doi:10.1016/j.earlhumdev.2004.01.003. [Context Link]

 

41. Phillips RM, Chantry CJ, Gallagher MP. Analgesic effects of breast-feeding or pacifier use with maternal holding in term infants. Ambul Pediatr. 2005;5(6):359-364. doi:10.1367/A04-189R.1. [Context Link]

 

42. Shendurnikar N, Gandhi K. Analgesic effects of breast-feeding on heel lancing. Indian Pediatr. 2005;42(7):730-732. [Context Link]

 

43. Efe E, Savaser S. The effect of two different methods used during peripheral venous blood collection on pain reduction in neonates. Agri. 2007;19(2):49-56. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L46861313. [Context Link]

 

44. Codipietro L, Ceccarelli M, Ponzone A. Breast-Feeding or oral sucrose solution in term neonates receiving heel lance: a randomized, controlled trial. Pediatrics. 2008;122(3):e716-e721. doi:10.1542/peds.2008-0221. [Context Link]

 

45. Leite AM, Linhares MBM, Lander J, Castral TC, dos Santos CB, Silvan Scochi CG. Effects of breast-feeding on pain relief in full-term newborns. Clin J Pain. 2009;25(9):827-832. doi:10.1097/AJP.0b013e3181b51191. [Context Link]

 

46. Weissman A, Aranovitch M, Blazer S, Zimmer EZ. Heel-lancing in newborns: behavioral and spectral analysis assessment of pain control methods. Pediatrics. 2009;124(5):e921-e926. doi:10.1542/peds.2009-0598. [Context Link]

 

47. Okan F, Ozdil A, Bulbul A, Yapici Z, Nuhoglu A. Analgesic effects of skin to skin contact and breast-feeding in procedural pain in healthy term neonates. Ann Trop Paediatr. 2010;30(2):119-128. doi:10.1179/146532810x12703902516121. [Context Link]

 

48. Efe E, Ozer ZC. The use of breast-feeding for pain relief during neonatal immunization injections. Appl Nurs Res. 2007;20(1):10-16. doi:10.1016/j.apnr.2005.10.005. [Context Link]

 

49. Stevens B, Johnston C, Taddio A, Gibbins S, Yamada J. The premature infant pain profile: evaluation 13 years after development. Clin J Pain. 2010;26(9):813-830. doi:10.1097/AJP.0b013e3181ed1070; 10.1097/AJP.0b013e3181ed1070. [Context Link]

 

50. Carbajal R, Paupe A, Hoenn E, Lenclen R. DAN: une echelle comportementale d'evaluation de la douleur aigui du nouveau-ne. Arch Pediatr. 1997;4:623-628. [Context Link]

 

51. Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulberg C. The development of a tool to assess neonatal pain. Neonatal Netw. 1993;12(6):59-66. http://ezproxy.library.dal.ca/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=c8h&AN=107476153&site=ehost-live. [Context Link]

 

52. Grunau RV, Craig KD. Pain expression in neonates: facial action and cry. Pain. 1987;28(3):395-410. doi:0304-3959(87)90073-X [pii]. [Context Link]

 

53. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ. What is "quality of evidence" and why is it important to clinicians? BMJ. 2008;336(7651):995-998. doi:10.1136/bmj.39490.551019.BE. [Context Link]

 

54. Skogsdal Y, Eriksson M, Schollin J. Analgesia in newborns given oral glucose. Acta Paediatr. 1997;86(2):217-220. [Context Link]

 

55. Ors R, Ozek E, Baysoy G, et al Comparison of sucrose and human milk on pain response in newborns. Eur J Pediatr. 1999;158(1):63-66. [Context Link]

 

56. Bucher HU, Baumgartner R, Bucher N, Seiler M, Fauchere JC. Artificial sweetener reduces nociceptive reaction in term newborn infants. Early Hum Dev. 2000;59(1):51-60. [Context Link]

 

57. Jatana SK, Dalal SS, Wilson CG. Analgesic effect of oral glucose in neonates. Med J Armed Forces India. 2003;59(2):100-104. http://http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L36503263. [Context Link]

 

58. Uyan ZS, Ozek E, Bilgen H, Cebeci D, Akman I. Effect of foremilk and hindmilk on simple procedural pain in newborns. Pediatr Int. 2005;47(3):252-257. doi:10.1111/j.1442-200x.2005.02055.x. [Context Link]

 

59. Mathai S, Natrajan N, Rajalakshmi NR. A comparative study of non-pharmacological methods to reduce pain in neonates. Indian Pediatr. 2006;43:1070-1075. [Context Link]

 

60. Ozdogan T, Akman I, Cebeci D, Bilgen H, Ozek E. Comparison of two doses of breast milk and sucrose during neonatal heel prick. Pediatr Int. 2010;52(2):175-179. doi:10.1111/j.1442-200X.2009.02921.x. [Context Link]

 

61. Upadhyay A, Aggarwal R, Narayan S, Joshi M, Paul VK, Deorari AK. Analgesic effect of expressed breast milk in procedural pain in term neonates: a randomized, placebo-controlled, double-blind trial. Acta Paediatr. 2004;93(4):518-522. doi:10.1080/08035250410022792. [Context Link]

 

62. Yilmaz F, Arikan D. The effects of various interventions to newborns on pain and duration of crying. J Clin Nurs. 2011;20(7-8):1008-1017. doi:10.1111/j.1365-2702.2010.03356.x. [Context Link]

 

63. Blass EM, Miller LW. Effects of colostrum in newborn humans: dissociation between analgesic and cardiac effects. J Dev Behav Pediatr. 2001;22(6):385-390. doi:10.1097/00004703-200112000-00006. [Context Link]

 

64. Harrison D, Sampson M, Reszel J, et al Too many crying babies: a systematic review of pain management practices during immunizations on YouTube. BMC Pediatr. 2014;14:134. doi:10.1186/1471-2431-14-134. [Context Link]

 

65. Liberati A, Altman DG, Tetzlaff J, et al The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1-e34. doi:10.1016/j.jclinepi.2009.06.006. [Context Link]

 

66. Higgins JPT, Altman DG, Gotzsche PC, et al The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi:10.1136/bmj.d5928. [Context Link]

 

67. Sterne JA, Hernan MA, Reeves BC, et al ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi:10.1136/bmj.i4919. [Context Link]

 

68. Guyatt GH, Oxman AD, Vist G, et al GRADE guidelines: 4. Rating the quality of evidence-study limitations (risk of bias). J Clin Epidemiol. 2011;64(4):407-415. doi:10.1016/j.jclinepi.2010.07.017. [Context Link]

 

69. Boroumandfar K, Khodaei F, Abdeyazdan Z, Maroufi M. Comparison of vaccination-related pain in infants who receive vapocoolant spray and breast-feeding during injection. Iran J Nurs Midwifery Res. 2013;18(1):33-37. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3748552&tool=pmcentrez&rendertype=abstract. [Context Link]

 

70. Gupta NK, Upadhyay A, Agarwal A, Goswami G, Kumar J, Sreenivas V. Randomized controlled trial of topical EMLA and breast-feeding for reducing pain during wDPT vaccination. Eur J Pediatr. 2013;172(11):1527-1533. doi:10.1007/s00431-013-2076-6. [Context Link]

 

71. Bembich S, Davanzo R, Brovedani P, Clarici A, Massaccesi S, Demarini S. Functional neuroimaging of breast-feeding analgesia. Int J Dev Neurosci. 2012;30(8):677-678. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L71828249. [Context Link]

 

72. Goswani G, Upadhyay A, Gupta N, Chaudhry R, Chawla D, Sceenivas V. Comparison of analgesic effect of direct breast-feeding, oral 25% dextrose solution, and placebo during first DPT vaccination in health term infants: a randomized placebo controlled trial. Indian Pediatr. 2013;50(4):649-653. [Context Link]

 

73. Chiabi A, Eloundou E, Mah E, Nguefack S, Mekone I, Mbonda E. Evaluation of breast-feeding and 30% glucose solution as analgesic measures in indigenous African term neonates. J Clin Neonatol. 2016;5(1):46-50. doi:10.4103/2249-4847.173269. [Context Link]

 

74. Fallah R, Naserzadeh N, Ferdosian F, Binesh F. Comparison of effect of kangaroo mother care, breast-feeding and swaddling on Bacillus Calmette-Guerin vaccine injection pain score in healthy term neonates by a clinical trial. J Matern Neonatal Med. 2016;7058:1-13. doi:10.1080/14767058.2016.1205030. [Context Link]

 

75. Marin Gabriel MA, del Rey Hurtado de Mendoza B, Jimenez Figueroa L, et al Analgesia with breast-feeding in addition to skin to skin contact during heel prick. Arch Dis Child Fetal Neonatal Ed. 2013;98:F499-F503. doi:10.1136/archdischild-2012-302921. [Context Link]

 

76. Modarres M, Jazayeri A, Rahnama P, Montazeri A. Breast-Feeding and pain relief in full-term neonates during immunization injections: a clinical randomized trial. BMC Anesthesiol. 2013;13(1):22. doi:10.1186/1471-2253-13-22. [Context Link]

 

77. Obeidat HM, Shuriquie MA. Effect of breast-feeding and maternal holding in relieving painful responses in full-term neonates. J Perinat Neonatal Nurs. 2015;29(3):248-254. doi:10.1097/JPN.0000000000000121. [Context Link]

 

78. Thomas T, Shetty AP, Bagali PV. Role of breast-feeding in pain response during injectable immunisation among infants. Nurs J India. 2011;102(8):184-186. [Context Link]

 

79. Zhu J, Hong-Gu H, Zhou X, et al Pain relief effect of breast-feeding and music therapy during heel lance for healthy-term neonates in China: a randomized controlled trial. Midwifery. 2015;31(3):365-372. doi:10.1016/j.midw.2014.11.001. [Context Link]

 

80. Lima AH, Hermont AP, Friche AA. Analgesia in newborns: a case-control study of the efficacy of nutritive and non-nutritive sucking stimuli. Codas. 2013;25(4):365-368. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L373966002. [Context Link]

 

81. Cordero MJA, Villar NM, Garcia IG, Lopez MAR, Baeza MMR. Oral glucose and breast milk as a strategy for pain reduction during the heel lance procedure in newborns. Nutr Hosp. 2014;30(5):1071-1076. doi:10.3305/nh.2014.30.5.7862. [Context Link]

 

82. Sahoo JP, Rao S, Nesargi S, Ranjit T, Ashok C, Bhat S. Expressed breast milk vs 25% dextrose in procedural pain in neonates: a double blind randomized controlled trial. Indian Pediatr. 2013;50(2):203-207. doi:10.1007/s13312-013-0067-3. [Context Link]

 

83. Sabety F, Yaghoobi M, Torabizadeh M, Javaherizadeh H, Haghighizadeh MH, Mohammadian F. Which is better for pain reduction before venipuncture: glucose, lidocaine or expressed breast milk? Hong Kong J Paediatr. 2013;18(1):19-23. [Context Link]

 

84. Bembich S, Davanzo R, Brovedani P, Clarici A, Massaccesi S, Demarini S. Functional neuroimaging of breast-feeding analgesia by multichannel near-infrared spectroscopy. Neonatology. 2013;104(4):255-259. http://www.embase.com/search/results?subaction=viewrecord&from=export&pid=L603959907. [Context Link]

 

85. Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature. 2001;412(6843):150-157. doi:10.1038/35084005. [Context Link]

 

86. Bueno M, Stevens B, de Camargo PP, Toma E, Krebs VLJ, Kimura AF. Breast milk and glucose for pain relief in preterm infants: a noninferiority randomized controlled trial. Pediatrics. 2012;129(4):664-670. doi:10.1542/peds.2011-2024. [Context Link]

 

87. Simonse E, Mulder PGH, van Beek RHT. Analgesic effect of breast milk versus sucrose for analgesia during heel lance in late preterm infants. Pediatrics. 2012;129(4):657-663. doi:10.1542/peds.2011-2173. [Context Link]

 

88. Ou-Yang MC, Chen IL, Chen CC, Chung MY, Chen FS, Huang HC. Expressed breast milk for procedural pain in preterm neonates: a randomized, double-blind, placebo-controlled trial. Acta Paediatr. 2013;102(1):15-21. doi:10.1111/apa.12045. [Context Link]

 

89. Nanavati RN, Balan R, Kabra NS. Effect of kangaroo mother care vs expressed breast milk administration on pain associated with removal of adhesive tape in very low-birth-weight neonates: a randomized controlled trial. Indian Pediatr. 2013;50(11):1011-1015. doi:10.1007/s13312-013-0280-0. [Context Link]

 

90. Holsti L, Oberlander TF, Brant R. Does breast-feeding reduce acute procedural pain in preterm infants in the neonatal intensive care unit? A randomized clinical trial. Pain. 2011;152(11):2575-2581. doi:10.1016/j.pain.2011.07.022. [Context Link]

 

91. Rosali L, Nesargi S, Mathew S, Vasu U, Sp R, Bhat S. Efficacy of expressed breast milk in reducing pain during ROP screening a randomized controlled trial. PubMed Commons. 2015;61(2):2014-2015. doi:10.1093/tropej/fmu073. [Context Link]

 

92. Blass EM, Shide DJ, Weller A. Stress-reducing effects of ingesting milk, sugars, and fats. A developmental perspective. Ann N Y Acad Sci. 1989;575:292-305. doi:10.1111/j.1749-6632.1989.tb53251.x. [Context Link]

 

93. Ren K, Blass EM, Zhou Q, Dubner R. Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats. Proc Natl Acad Sci U S A. 1997;94(4):1471-1475. doi:10.1073/pnas.94.4.1471. [Context Link]

 

94. Shide DJ, Blass EM. Opioidlike effects of intraoral infusions of corn oil and polycose on stress reactions in 10-day-old rats. Behav Neurosci. 1989;103(6):1168-1175. http://ezproxy.library.dal.ca/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=psyh&AN=1990-09365-001&site=ehost-live. [Context Link]

 

95. Stevens B, Yamada J, Gy L, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2016;(7), 1-355. CD001069, doi:CD001069 [pii]\r10.1002/14651858.CD001069. [Context Link]

 

96. Bueno M, Yamada J, Harrison D, et al A systematic review and meta-analyses of nonsucrose sweet solutions for pain relief in neonates. Pain Res Manag. 2013;18(3):153-161. [Context Link]

 

97. Blass EM, Ciaramitaro V. A new look at some old mechanisms in human newborns: taste and tactile determinants of state, affect, and action. Monogr Soc Res Child Dev. 1994;59(1):I-V, 1-81. [Context Link]

 

98. Stevens B, Taddio A, Ohlsson A, Einarson T. The efficacy of sucrose for relieving procedural pain in neonates-a systematic review and meta-analysis. Acta Paediatr Int J Paediatr. 1997;86(8):837-842. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L27342727%5Cnhttp://sfxhosted.exlibrisgroup.com/dal?sid=EMBASE&issn=08035253&id=doi:&atitle=The+efficacy+of+sucrose+for+relieving+procedural+pain+in+neonates+-+A+systematic+review+and+. [Context Link]

 

99. Johnston C, Campbell-Yeo M, Fernandes A, Inglis D, Streiner D, Zee R. Skin to skin care for procedural pain in neonates. Cochrane Database Syst Rev. 2014;1:CD008435. doi:10.1002/14651858.CD008435.pub2. [Context Link]

 

100. Goubet N, Rattaz C, Pierrat V, Bullinger A, Lequien P. Olfactory experience mediates response to pain in preterm newborns. Dev Psychobiol. 2003;42(2):171-180. doi:10.1002/dev.10085. [Context Link]

 

101. Goubet N, Strasbaugh K, Chesney J. Familiarity breeds content? Soothing effect of a familiar odor on full-term newborns. J Dev Behav Pediatr. 2007;28(3):189-194. doi:10.1097/dbp.0b013e31802d0b8d. [Context Link]

 

102. Pillai Riddell RR, Racine NM, Gennis HG, et al Non-pharmacological management of infant and young child procedural pain (review). Cochrane Database Syst Rev. 2015;(12)CD006275. doi:10.1002/14651858.CD006275. doi: 10.1002/14651858.CD006275.pub3. [Context Link]

 

103. Johnston CC, Filion F, Snider L, et al Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks' postconceptional age. Pediatrics. 2002;110(3):523-528. [Context Link]

 

104. Johnston CC, Filion F, Snider L, et al How much sucrose is too much sucrose? Pediatrics. 2007;119(1):226. doi:10.1542/peds.2006-3001. [Context Link]

 

105. Kramer MS, Kakuma R. Optimal duration of exclusive breast-feeding. Cochrane Database Syst Rev. 2002;(1):CD003517. doi:10.1002/14651858.CD003517. [Context Link]

 

106. Kramer MS, Aboud F, Mironova E, et al Breast-Feeding and child cognitive development: new evidence from a large randomized trial. Arch Gen Psychiatry. 2008;65(5):578-584. doi:10.1001/archpsyc.65.5.578. [Context Link]

 

107. Ip S, Chung M, Raman G, et al Breast-Feeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess (Full Rep). 2007;(153):1-186. [Context Link]

 

108. Owen CG, Martin RM, Whincup PH, Smith GD, Cook DG. Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics. 2005;115(5):1367-1377. doi:115/5/1367 [pii]. [Context Link]

 

109. Das UN. Breast-Feeding prevents type 2 diabetes mellitus: but, how and why? Am J Clin Nutr. 2007;85(5):1436-1437. doi:85/5/1436 [pii]. [Context Link]

 

110. Rosenbauer J, Herzig P, Giani G. Early infant feeding and risk of type 1 diabetes mellitus-a nationwide population-based case-control study in pre-school children. Diabetes Metab Res Rev. 2008;24(3):211-222. doi:10.1002/dmrr.791. [Context Link]

 

111. Akobeng AK, Ramanan AV, Buchan I, Heller RF. Effect of breast-feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child. 2006;91(1):39-43. doi:adc.2005.082016 [pii]. [Context Link]

 

112. Barclay AR, Russell RK, Wilson ML, Gilmour WH, Satsangi J, Wilson DC. Systematic review: the role of breast-feeding in the development of pediatric inflammatory bowel disease. J Pediatr. 2009;155(3):421-426. doi:10.1016/j.jpeds.2009.03.017. [Context Link]

 

113. Danforth KN, Tworoger SS, Hecht JL, Rosner BA, Colditz GA, Hankinson SE. Breast-Feeding and risk of ovarian cancer in two prospective cohorts. Cancer Causes Control. 2007;18(5):517-523. doi:10.1007/s10552-007-0130-2. [Context Link]

 

114. Gabriel MAM, Martin IL, Escobar AL, Villalba EF, Blanco IR, Pol PT. Randomized controlled trial of early skin to skin contact: effects on the mother and the newborn. Acta Paediatr Int J Paediatr. 2010;99(11):1630-1634. doi:10.1111/j.1651-2227.2009.01597.x. [Context Link]

 

115. Slater R, Cornelissen L, Fabrizi L, et al Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet. 2010;376(9748):1225-1232. doi:10.1016/S0140-6736(10)61303-7. [Context Link]

 

116. Edwards P, Clarke M, DiGuiseppi C, Pratap S, Roberts I, Wentz R. Identification of randomized controlled trials in systematic reviews: accuracy and reliability of screening records. Stat Med. 2002;21(11):1635-1640. doi:10.1002/sim.1190. [Context Link]

 

117. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2002;6(6):e1000097. doi:10.1371/journal.pmed1000097. [Context Link]

 

The CE test for this article is available online only. Log onto the journal website, http://www.JPNONline.com, or to http://www.NursingCenter.com/CE/JPN to access the test. For 16 additional continuing education articles related to breastfreeding topics, go to http://NursingCenter.com\CE.

 

breast-feeding; expressed breast milk; infants; procedural pain; systematic review