We investigated how well breastfeeding or supplemental breast milk (expressed breast milk given via feeding tube or by placing breast milk in baby's mouth) works as a pain reliever in newborn babies while they undergo painful procedures (e.g. vaccination, heel prick, blood sampling for tests or eye examinations). The babies' pain responses (e.g. changes in heart rate, oxygen level, blood pressure, percentages of crying time, duration of crying etc.) were assessed by health care professionals to measure the pain that babies are experiencing.
Breastfeeding may provide pain relief for newborn babies undergoing painful procedures. Medication for pain relief is commonly given for major painful procedures, but may not be given for minor painful procedures such as blood sampling (by heel prick or taking a sample from a vein). There are different forms of non-drug strategies that can be used to reduce pain in babies, such as holding or swaddling them, sucking on a pacifier, or giving sweet solutions (such as sucrose or glucose). Different studies done in newborn babies have shown that breastfeeding may be a good way to reduce the pain they feel when subjected to minor painful procedures. These studies have been done in full-term babies, and they have shown that breastfeeding may be effective by demonstrating that it reduces babies' crying time and various pain scores that have been validated for babies. Breast milk given by syringe has not shown the same efficacy as breastfeeding itself. Very few studies have been done in preterm babies, and so new studies are needed to determine if the use of supplemental breast milk in these small babies is effective in reducing their pain.
We searched the medical literature thoroughly up to 1 August 2022 for studies that investigated the pain-relieving effect of breastfeeding or supplemental breast milk for minor medical procedures in newborn full-term and preterm neonates We included randomised trials only, as they provide the most reliable medical evidence. We identified 66 studies that reported on a total of more than 6200 infants in this Cochrane Review. Thirty-six studies evaluated breastfeeding, 29 studies evaluated supplemental breast milk, while one study compared both against each other. In over half of the studies, pain relief was during a heel prick procedure. In others, it was during vaccination, drawing blood from a vein or other procedures. The studies used a variety of comparative groups, for example, placebo, no intervention, maternal holding, skin-to-skin contact, similar volume of water, a pacifier, routine care, various concentrations of sucrose or glucose, 'facilitated tucking' (holding the infant in a flexed position with arms close to the body and hands placed to promote sucking), swaddling, heel warmth, anaesthetic cream for the skin, or a combination of these. The studies used a wide variety of pain scales as well as changes in heart rate and blood pressure and cry duration to assess pain.
Study funding sources
The studies included in the review were not externally funded according to information given in the reports.
Newborn babies in the breastfeeding group experienced a lower heart rate, shorter duration of cry, lower percentage of cry time and lower scores on the Neonatal Infant Pain Scale than babies who received no intervention. Moderate concentrations of glucose/sucrose may have similar effectiveness to breastfeeding. Studies of supplemental breast milk showed variable results. Supplemental breast milk was found to have a lower increase in heart rate when compared to water, and a lower duration of crying when compared to placebo.
What are the limitations of the evidence
We are moderately confident that breastfeeding reduces pain as assessed by heart rate, cry duration or validated pain scale compared to no intervention. Supplemental breast milk for painful procedures may reduce pain when compared to no intervention or placebo.
Due to the high number of comparator groups, other measures of pain were assessed in a very small number of studies. The majority of the studies did not report on any unwanted or harmful effects of treatment. Those that did this identified no unwanted or harmful effects of treatment in any infants.
Moderate-/low-certainty evidence suggests that breastfeeding or supplemental breast milk may reduce pain in neonates undergoing painful procedures compared to no intervention/positioning/holding or placebo or non-pharmacological interventions. Low-certainty evidence suggests that moderate concentration (20% to 33%) glucose/sucrose may lead to little or no difference in reducing pain compared to breastfeeding. The effectiveness of breast milk for painful procedures should be studied in the preterm population, as there are currently a limited number of studies that have assessed its effectiveness in this population.
Pain in the neonate is associated with acute behavioural and physiological changes. Cumulative pain is associated with morbidities, including adverse neurodevelopmental outcomes. Studies have shown a reduction in changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in neonates experiencing pain or stress. Non-pharmacological measures (such as holding, swaddling and breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for analgesia. This is an update of a review first published in 2006 and updated in 2012.
The primary objective was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, gestational age and the amount of supplemental breast milk given.
We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries (ICTRP, ISRCTN and clinicaltrials.gov) in August 2022; searches were limited from 2011 forwards. We checked the reference lists of included studies and relevant systematic reviews.
We included randomised controlled trials (RCTs) or quasi-RCTs of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates. We included both term (≥ 37 completed weeks postmenstrual age) and preterm infants (< 37 completed weeks' postmenstrual age) up to a maximum of 44 weeks' postmenstrual age. The study must have reported on either physiological markers of pain or validated pain scores.
We assessed the methodological quality of the trials using the information provided in the studies and by personal communication with the authors. We extracted data on relevant outcomes, estimated the effect size and reported this as a mean difference (MD). We used the GRADE approach to assess the certainty of evidence.
Of the 66 included studies, 36 evaluated breastfeeding, 29 evaluated supplemental breast milk and one study compared them against each other. The procedures conducted in the studies were: heel lance (39), venipuncture (11), intramuscular vaccination (nine), eye examination for retinopathy of prematurity (four), suctioning (four) and adhesive tape removal as procedure (one). We noted marked heterogeneity in the control interventions and pain assessment measures amongst the studies. Since many studies included multiple arms with breastfeeding/supplemental breast milk as the main comparator, we were not able to synthesise all interventions together. Individual interventions are compared to breastfeeding/supplemental breast milk and reported. The numbers of studies/participants presented with the findings are not taken from pooled analyses (as is usual in Cochrane Reviews), but are the overall totals in each comparison.
Overall, the included studies were at low risk of bias except for masking of intervention and outcome assessment, where nearly one-third of studies were at high risk of bias.
Breastfeeding versus control
Breastfeeding may reduce the increase in heart rate compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration of sucrose/glucose (20% to 33%) with skin-to-skin contact (low-certainty evidence, 8 studies, 784 participants).
Breastfeeding likely reduces the duration of crying compared to no intervention, lying on table, rocking, heel warming, holding by mother, skin-to-skin contact, bottle feeding mother's milk and moderate concentration of glucose (moderate-certainty evidence, 16 studies, 1866 participants).
Breastfeeding may reduce percentage time crying compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration sucrose and moderate concentration of sucrose with skin-to-skin contact (low-certainty evidence, 4 studies, 359 participants).
Breastfeeding likely reduces the Neonatal Infant Pain Scale (NIPS) score compared to no intervention, holding by mother, heel warming, music, EMLA cream, moderate glucose concentration, swaddling, swaddling and holding (moderate-certainty evidence, 12 studies, 1432 participants).
Breastfeeding may reduce the Neonatal Facial Coding System (NFCS) score compared to no intervention, holding, pacifier and moderate concentration of glucose (low-certainty evidence, 2 studies, 235 participants).
Breastfeeding may reduce the Douleur Aigue Nouveau-né (DAN) score compared to positioning, holding or placebo (low-certainty evidence, 4 studies, 709 participants).
In the majority of the other comparisons there was little or no difference between the breastfeeding and control group in any of the outcome measures.
Supplemental breast milk versus control
Supplemental breast milk may reduce the increase in heart rate compared to water or no intervention (low-certainty evidence, 5 studies, 336 participants).
Supplemental breast milk likely reduces the duration of crying compared to positioning, massage or placebo (moderate-certainty evidence, 11 studies, 1283 participants).
Supplemental breast milk results in little or no difference in percentage time crying compared to placebo or glycine (low-certainty evidence, 1 study, 70 participants).
Supplemental breast milk results in little or no difference in NIPS score compared to no intervention, pacifier, moderate concentration of sucrose, eye drops, gentle touch and verbal comfort, and breast milk odour and verbal comfort (low-certainty evidence, 3 studies, 291 participants).
Supplemental breast milk may reduce NFCS score compared to glycine (overall low-certainty evidence, 1 study, 40 participants). DAN scores were lower when compared to massage and water; no different when compared to no intervention, EMLA and moderate concentration of sucrose; and higher when compared to rocking or pacifier (low-certainty evidence, 2 studies, 224 participants).
Due to the high number of comparator interventions, other measures of pain were assessed in a very small number of studies in both comparisons, rendering the evidence of low certainty.
The majority of studies did not report on adverse events, considering the benign nature of the intervention. Those that reported on adverse events identified none in any participants.
Subgroup analyses were not conducted due to the small number of studies.