Comparative Efficacy of Breastfeeding or Feeding of Breast Milk on Blood Sampling Pain Relief in Full-Term Neonates: A Systematic Review and Meta-Analysis

Abstract

Objectives:

To evaluate the efficacy of breastfeeding or feeding of breast milk in reducing blood sampling pain in full-term neonates by comparing with other intervention measures.

Methods:

Related literature was searched from PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (Central). Only randomized controlled trials (RCTs), which reported the effect of breastfeeding or feeding of breast milk on blood sampling pain in full-term neonates, were eligible. The primary outcome was set as pain score on scales, and the secondary outcomes as physiological and behavioral indicators. The risk of bias in included studies was assessed by the Cochrane Collaboration's tool. Data analysis was performed using RevMan 5.4.1.

Main Results:

A total of 17 RCTs were included. Breastfeeding showed a stronger effectiveness in reducing blood sampling pain, compared with nonintervention, placebo, mother's holding, breast milk odor, mother's heartbeat, music therapy, skin-to-skin, and Eutectic Mixture of Local Anesthetics ointment. However, the efficacy of glucose or sucrose (12.5%–30% concentration) seems better than breastfeeding. When compared with other interventions, feeding of breast milk yielded different results. Its effect was only stronger than placebo (sterile water or distilled water), massage, or nonintervention.

Conclusions:

Breastfeeding might be effective for alleviating blood sampling pain in full-term neonates. Its effect is second only to that of glucose/sucrose. The efficacy of feeding of breast milk in reducing blood sampling pain in full-term neonates might not be guaranteed.

Introduction

Pain is defined as an unpleasant emotional and sensory experience associated with actual or potential tissue damage.¹ Studies have demonstrated that neonates can not only feel pain, but also exhibit heightened sensitivity to painful stimuli, as their nervous systems are immature.² It is difficult to evaluate the pain in neonates, due to their inability to describe pain verbally. Therefore, it has suggested that the pain in neonates can be indirectly evaluated with behavioral and physiological parameters.³ These parameters have been compiled into various scales for pain assessment.

Pain increases the risk of neurodevelopmental disorders in neonates.⁴ Two methods are commonly taken to reduce the pain in neonates receiving clinical procedures, including pharmacological analgesia and nonpharmacological intervention. The former refers to the use of acetaminophen^5,6 and opioid analgesics. The latter involves massage, skin-to-skin,⁷ cuddling (mother's holding), oral sucrose water, breastfeeding,⁸ non-nutritional sucking,⁹ etc. Studies have shown that these measures could significantly alleviate pain.¹⁰ In addition, sucrose is also effective in mitigating procedural pain in neonates.¹¹

Breastfeeding or feeding of breast milk is safe and accessible. However, normal breast milk contains only 7% lactose, potentially limiting its effectiveness compared with higher concentrations of glucose or sucrose. In contrast, nonpharmacological interventions such as non-nutritive sucking (NNS) or mother's holding may yield similar effects to that of breastfeeding or feeding of breast milk. Therefore, in this review, we meta-analyzed the effectiveness of breastfeeding or feeding of breast milk in reducing pain associated with blood sampling procedures in full-term neonates.

Materials and Methods

Objectives

Our overall objectives were to (1) compare breastfeeding with control interventions (placebo, nonintervention, glucose, sucrose, NNS, mother's holding, music therapy, massage, EMLA ointment, skin-to-skin, breast milk odor, and mother's heartbeat) and (2) compare feeding of breast milk with control interventions (placebo, massage, rocking, nonintervention, glucose, sucrose, NNS, breast milk odor, and mother's holding) in reducing blood sampling pain among neonates. The pain was assessed by physiological (heart rate and oxygen saturation), behavioral parameters (cry duration, proportion of time crying, and duration of the first cry), or scoring scales.

Data sources

We searched related literature from the PubMed (1946–March 2023), EMBASE (1973–March 2023), Web of Science (1928–March 2023), and Cochrane Central Register of Controlled Trials (Central) (The Cochrane Library 2023, Issue 1). Excluded were letters, editorials, reviews, lectures, and commentaries.

Study selection

Included were randomized controlled trials (RCTs) that reported the effects of breastfeeding or feeding of breast milk to alleviate procedural pain in full-term neonates undergoing blood sampling through heel lance or venipuncture.

Data extraction

Data were extracted from the eligible studies independently by two reviewers (C.P.S. and J.T.). Discrepancies were resolved by reaching a consensus or discussion with a third author (W.B.T.). The methodological quality of each included trial was assessed using the Cochrane Handbook, which encompasses seven domains: generation of randomization sequences, allocation concealment, blinding of participants and implementers, blinding of outcome assessment, incomplete outcome data, selective reporting, and other potential biases (Fig. 1).

FIG. 1.

Risk of bias among the 17 included studies. The green background with “+” means a low risk of bias; the red background with “−” means a high risk of bias; the yellow background with “?” means unknown risk of bias. Trials involving three or more high risks of bias were considered to have a poor methodological quality.

Typical effect size was calculated as mean difference (MD) and with a 95% confidence interval (CI) as appropriate. All analyses were conducted using RevMan 5.4.1 software (Cochrane Collaboration). The I² test for between-study heterogeneity was employed to evaluate the appropriateness of study pooling.

Results

A total of 17 studies were eligible (Fig. 2), including 10 studies about breastfeeding and 8 studies about feeding of breast milk. One of the 17 studies compared breastfeeding with feeding of breast milk. Sampling was performed through heel lance in 14 studies and venipuncture in 3 studies. The data regarding the participants, interventions, and outcomes are given in Table 1 (breastfeeding) and Table 2 (feeding of breast milk).

FIG. 2.

Flow chart of selection of studies.

Table 1.

Characteristics of Randomized Controlled Trials Evaluating the Pain-Reducing Effects of Breastfeeding

Author	Carbajal	Codipietro	Leite	Obeidat	Zhu	Chiabi	Soltani	Chang	Tavlar
Year of study	2003	2008	2009	2015	2015	2016	2018	2020	2022
Type of study	RCT	RCT	RCT	RCT	RCT	RCT	RCT	RCT	RCT
Infants
Birth weight(g)	N/A	N/A	N/A	N/A	2,000–4,000	N/A	2,500–4,000	N/A	2,500–4,000
Gestational age (weeks)	Term	37–42	Term	38–42	Term	Term	37–42	Term	38–42
Study groups
Group 1	Breastfeeding	Breastfeeding	Breastfeeding	Breastfeeding	Breastfeeding	Breastfeeding	Breastfeeding	Breastfeeding	Breastfeeding
Group 2	Cuddled in mother's arms	25% Sucrose	Held by the mother	Control	Classical music	30% glucose	25% Dextrose	24% Sucrose	Mother's heartbeat sounds
Group 3	Sterile water	N/A	N/A	N/A	Breastfeeding and classical music	N/A	Kangaroo mother care	Non-nutritive sucking (NNS)	Breast milk odor
Group 4	30% Glucose	N/A	N/A	N/A	Control	N/A	EMLA ointment	Skin-to-skin	N/A
Group 5	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Control	N/A
Group 6	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Outcomes assessment	DAN, PIPP	PIPP, heart rate change, duration of first cry,	NFCS, heart rate change	PIPP	NIPS, duration of first cry.	NIPS	NIPS	N-PASS, crying time	ALPS-Neo pain score, crying time

RCT, randomized controlled trial; N/A, not applicable; PIPP, premature infant pain profile; N-PASS, neonatal pain, agitation, and sedation scale; IBCS, infant body coding system; DAN, Douleur Aigue Nouveau-ne; NIPS, neonatal infant pain scale; NFCS, neonatal facial coding system.

Table 2.

Characteristics of Randomized Controlled Trials Evaluating the Pain-Reducing Effects of Feeding of Breast Milk

Author	Bilgen	Upadhyay	Uyan	Mathai	Ozdogan	Yilmaz	Wu	Erdoğan
Year of study	2001	2004	2005	2006	2010	2011	2021	2022
Type of study	RCT	RCT	RCT	RCT	RCT	RCT	RCT	RCT
Infants
Birth weight(g)	2,380–4,300	N/A	N/A	N/A	N/A	N/A	2,500–4,000	N/A
Gestational age (weeks)	37–42	37–41	Term	Term	Term	37–42	Term	Term
Study groups
Group 1	Breastfeeding	Distilled water	Foremilk	Feeding of breast milk	Single dose of feeding of breast milk	Feeding of breast milk	Feeding of breast milk	Feeding of breast milk
Group 2	Feeding of breast milk	Feeding of breast milk	Hindmilk	20% Sucrose	Single dose of 12.5% sucrose	20%Sucrose	Nonintervention	Breast milk odor
Group 3	25% Sucrose	N/A	Sterile water	Distilled water	Single dose of sterile water	Non-nutritive sucking (NNS)	N/A	Control
Group 4	Sterile water	N/A	N/A	Non-nutritive sucking (NNS)	Two-dose feeding of breast milk	Control	N/A	N/A
Group 5	N/A	N/A	N/A	Stroking	Two-dose 12.5%sucrose	N/A	N/A	N/A
Group 6	N/A	N/A	N/A	Be rocked	Two-dose sterile water	N/A	N/A	N/A
Outcomes assessment	IBCS, crying time	NFCS, crying time	NFCS, crying time, percent change in heart rate	DAN, time of first cry	NFCS, crying time	NIPS,crying time	NIPS, crying time	N-PASS

Breastfeeding versus control

Pain scales

Douleur Aigue Nouveau-né score scale

The Douleur Aigue Nouveau-né (DAN) scale was used in only one study.¹² The score in the breastfeeding group was statistically significantly lower than those in the sterile water group (MD, −6.31; 95% CI: −8.22 to −4.40) and the mother's holding group (MD, −7.08; 95% CI: −7.92 to −6.24) (Supplementary Fig. S1A, B). The scores were not significantly different between the breastfeeding group and the 30% glucose group (MD, −0.96; 95% CI: −2.05 to 0.13) (Supplementary Fig. S1C).

Infant body coding system scale

The infant body coding system (IBCS) scale was also used in only one study.¹³ The IBCS was significantly higher in the breastfeeding group than in the 25% sucrose group (p = 0.001), but showed no significant difference between those in the sterile water group (p = 0.4) and those in the feeding of breast milk group (p = 0.7).

Premature infant pain profile scale

The premature infant pain profile (PIPP) scale was utilized in three studies.^12,14,15 The PIPP score was significantly higher in the breastfeeding group than in the sterile water group (MD, −5.89; 95% CI: −7.37 to −4.41) (Supplementary Fig. S2A), the be hugged group (MD, −7.35; 95% CI: −8.86 to −55.84) (Supplementary Fig. S2B), the 25% sucrose group (p < 0.001), and the nonintervention group (p < 0.001), but not significantly different from that in the 30% glucose group (MD, 1.12; 95% CI: −0.42 to 2.66) (Supplementary Fig. S2C).

Neonatal pain, agitation, and sedation scale

One study reported the application of Neonatal Pain, Agitation, and Sedation Scale (N-PASS).¹⁶ The N-PASS score was statistically significantly lower in the breastfeeding group than in the nonintervention group (p < 0.01), but not significantly different from those in the 25% sucrose group (p = 0.24), the skin-to-skin group (p = 0.1), and the NNS group (p = 0.74).

Neonatal infant pain score

The pain was evaluated with neonatal infant pain score (NIPS) in three studies.^17–19 The NIPS during sampling procedures was significantly lower in the breastfeeding group than in the 30% glucose group (p < 0.001), but there was no significant between-group difference at 2 minutes after the procedure (p = 0.87).¹⁸ The NIPSs were significantly higher in the nonintervention and music therapy groups than in the breastfeeding group during and at 1 minute after the procedure (p < 0.001), but there was no significant between-group difference at 5 minutes after the procedure (p = 0.065).¹⁷ The NIPS score in the breastfeeding group was significantly lower than that in the skin-to-skin group, the EMLA ointment group, or in the 25% sucrose group (p < 0.001).¹⁹

Neonatal facial coding system

One study reported the analysis of Neonatal Facial Coding System (NFCS) scores.²⁰ The score was statistically significantly lower in the breastfeeding group than in the mother's holding group (p < 0.001).

ALPS-Neo pain score

One study reported the analysis of ALPS-Neo scores.²¹ The ALPS-Neo pain score was significantly lower in the breastfeeding group than in the breast milk odor or mother's heartbeat group during or after the sampling procedure (p < 0.001).

Physiological parameters

Heart rate (beats per minute)

In two studies,^13,14 heart rate was adopted to evaluate the pain during or after the heel lance. The heart rate increased in every group at 1 minute after the procedure, more significantly in the breastfeeding group than in the 25% sucrose group (MD, 19.9; 95% CI: 8.75–31.05) (Supplementary Fig. S3A), but there was no significant difference between the breastfeeding and sterile water groups (MD, 5.31; 95% CI: −11 to 21.62)¹³ (Supplementary Fig. S3B). Codipietro et al. reported that at 30 seconds after the procedure, the increase of heart rate was significantly higher in the breastfeeding group than in the 25% sucrose group (p = 0.005).

Oxygen saturation

One study reported the changes in oxygen saturation during heel lance.¹⁴ Oxygen saturation decreased in both the breastfeeding group and the 25% sucrose group, less significantly in the former (p = 0.001).

Heart rate recovery time

One study¹³ reported that after heel lance, the heart rate recovery time (in seconds) was significantly longer in the breastfeeding group than in the 25% sucrose group (p = 0.02). But there was no significant difference between the breastfeeding and the placebo groups (sterile water) (p = 0.44).

Cry variables

Percentage of crying time

Codipietro et al. reported that during heel lance, the percentage of crying time decreased significantly in the breastfeeding group, compared with that in the oral 25% sucrose group (p < 0.001).¹⁴

Crying duration

Three studies^13,16,21 reported no statistically significant difference in the crying duration (in seconds) (MD, 42.31; 95% CI −3.54 to 88.16) between the breastfeeding group and the 25% sucrose group^13,16 (Supplementary Fig. S4A), but the crying duration was reduced in the breastfeeding group, compared with that in the sterile water group (p < 0.008).¹³ The breastfeeding group demonstrated a significant reduction in the crying duration, compared with nonintervention group (MD, −203.4; 95% CI: −279.88 to −126.92)¹⁶ (Supplementary Fig. S4B).

Meanwhile, there was no significant difference in the crying duration between the breastfeeding group and the NNS group (MD, 7.8; 95% CI: −63.74 to 79.34) or the skin-to-skin group (MD, −9.00; 95% CI: −71.82 to 53.82)¹⁶ (Supplementary Fig. S4C, D). Crying duration was reduced in the breastfeeding group during or after the heel lance, compared with that in the breast milk odor group or mother's heartbeat group (p < 0.001).²¹

First cry duration

Two studies^14,17 reported the duration (in seconds) of the first cry. Codipietro et al. reported that the first cry duration was reduced in the breastfeeding group, compared with that in the 25% sucrose group (p < 0.001).^14,17 Zhu et al. reported a significantly shorter first cry in the breastfeeding group than in the nonintervention group and the music therapy group (p < 0.001).^14,17

Feeding of breast milk versus control

Pain scales

IBCS score

One study¹³ reported the analysis of IBCS score. The IBCS score was significantly higher in the feeding of breast milk group than in the 25% sucrose group (p = 0.001), but not significantly different from that in the sterile water group (p = 0.24).

Neonatal facial coding system

The pain was evaluated with NFCS in three studies.^22–24 No significant difference was found between the feeding of breast milk group and the placebo group immediately (MD, −0.45; 95% CI: −1.00 to 0.11)^22,23 or 1 minute (MD, −0.72; 95% CI: −1.67 to 0.24)^22–24 after the sampling procedure, but there was a significant reduction in the NFCS in the feeding of breast milk group when compared with the placebo group at 2 minutes (MD, −0.80; 95% CI: −1.16 to −0.43)^23,24 or 3 minutes (MD, −1.20; 95% CI: −1.58 to −0.83)^22–24 after the procedure (Fig. 3).

FIG. 3.

Subgroup analysis: feeding of breast milk versus control. Comparison of feeding of breast milk group and placebo group immediately, 1 minute, 2 minutes, and 3 minutes after the blood sampling by using NFCS. NFCS, neonatal facial coding system.

Ozdogan et al. reported that the NFCS scores were significantly higher in the feeding of breast milk group at 1 minute (MD, 0.94; 95% CI: 0.50 to 1.38) (Supplementary Fig. S5 A), 2 minutes (MD, 0.92; 95% CI: 0.49 to 1.35) (Supplementary Fig. S5B), and 3 minutes (MD, 1.43; 95% CI: 0.98–1.88) (Supplementary Fig. S5C) after the procedure, when compared with those in the 12.5% sucrose group.²⁴

DAN score

One study reported the DAN scores at 2 minutes.²⁵ The DAN score dropped significantly in the feeding of breast milk group, compared with the distilled water group (MD, −1.10; 95% CI: −1.65 to −0.55) (Supplementary Fig. S6A) and the massage group (MD, −0.50; 95% CI: −0.91 to −0.09) (Supplementary Fig. S6B). There was no significant difference between the feeding of breast milk group and the 20% sucrose group (MD, 0.10; 95% CI: −0.30 to 0.50) (Supplementary Fig. S6C). The DAN score was significantly higher in the feeding of breast milk group than in the NNS group (MD, 0.80; 95% CI: 0.40–1.20) (Supplementary Fig. S6D), and in the rocking group (MD, 1.10; 95% CI: 0.65–1.55) (Supplementary Fig. S6E).

Neonatal infant pain score

The pain was measured by NIPS in two studies.^26,27 No significant difference was found between the feeding of breast milk group and the 20% sucrose group during the procedure (p > 0.05), but the NIPS was significantly higher in the feeding of breast milk group after the procedure (p < 0.05). No statistical difference was found between the feeding of breast milk group and the nonintervention group (MD, −1.23; 95% CI: −3.53 to 1.07) (Supplementary Fig. S7), or the NNS (pacifier) group during the procedure (p > 0.05).

Neonatal pain, agitation, and sedation scale

Only one study reported the assessment with this index.²⁸ Erdogan et al. reported a statistically significant reduction in the N-PASS score in the feeding of breast milk group, compared with the nonintervention group and the breast milk odor group during or after the procedure (p < 0.001).

Physiological parameters

Heart rate (beats per minute)

Heart rate was adopted to evaluate the pain in two studies.^13,26 Bilgen et al. reported a significantly higher increase in the heart rate in the feeding of breast milk group than in the 25% sucrose group (MD, 13.95; 95% CI: 4.06–22.78) (Supplementary Fig. S8A). But there was no significant difference between the feeding of breast milk group and the sterile water group during (MD, −3.15; 95% CI: −10.91 to 4.61) (Supplementary Fig. S8B) or 1 minute after the procedure (MD, −1.14; 95% CI: −14.70 to 12.42) (Supplementary Fig. S8C).¹³ Yilmaz et al. also showed no difference between the feeding of breast milk group, the 20% sucrose group, the NNS group, or the nonintervention group (p > 0.05).²⁶

Heart rate recovery time

Two studies^13,22 reported the analysis of this index. The heart rate recovery time (in seconds) was significantly higher in the feeding of breast milk group, compared with the 25% sucrose (p = 0.007), but no significant difference was found between the feeding of breast milk group and the sterile water group (MD, −46.93; 95% CI: −122.84 to 28.97) (Supplementary Fig. S9).

Cry variables

Crying duration

Seven studies^13,22–27 reported the duration (in seconds) of crying. The data from five studies revealed a statistically significant reduction in the crying duration in the feeding of breast milk, compared with the one dose of the placebo group (MD, −10.06; 95% CI: −19.24 to −0.88)^13,22–25 (Fig. 4A). When comparing feeding of breast milk with two doses of placebo, no statistical difference was identified (MD, −2.80; 95% CI: −19.22 to 13.62)²⁴ (Supplementary Fig. S10A).

FIG. 4.

Effect of feeding of breast milk versus control on crying duration (in seconds). Comparison between feeding of breast milk group and placebo group (A). Comparison between feeding of breast milk group and 20% sucrose group (B). Comparison between feeding of breast milk group and NNS group (C). Comparison between feeding of breast milk group and nonintervention group (D). NNS, non-nutritive sucking.

Bilgen et al. observed a significant increase in the crying duration between the feeding of breast milk and the 25% sucrose group (p = 0.01),¹² but not between the feeding of breast milk group and the 20% sucrose group (MD, 38.04; 95% CI: −24.72 to 100.79)^25,26 (Fig. 4B). Mathai et al. reported a reduction in crying duration in the feeding of breast milk group, compared with the massage group (MD, −9.00; 95% CI: −16.97 to −1.03)²⁵ (Supplementary Fig. S10B).

The crying duration increased in the feeding of breast milk group, compared with the NNS group (MD, 44.23; 95% CI: 38.47–49.98) (Fig. 4C),^25,26 the rocking group²⁵ (MD, 31.00; 95% CI: 24.47–37.53) (Supplementary Fig. S10C), the single-dose 12.5% sucrose group (MD, 34.84; 95% CI: 25.30–44 38) (Supplementary Fig. S10D),²⁴ and the two-dose 12.5% sucrose group (MD, 30.80; 95% CI: 16.72–44.88)²⁵ (Supplementary Fig. S10E).

There was no difference in the crying duration between the single-dose feeding of breast milk group and the two-dose feeding of breast milk group (MD, 2.77; 95% CI: −13.30 to 18.84)²⁴ (Supplementary Fig. S10 F). No statistical difference was identified between the feeding of breast milk and the nonintervention group (MD, 3.27; 95% CI: −56.60 to 63.14)^26,27 (Fig. 4D).

First cry duration

Only two studies^23,25 assessed the duration (in seconds) of the first cry. No significant difference was found between the feeding of breast milk group and the placebo group (MD, 0.95; 95% CI: −4.85 to 6.74)^23,25 (Supplementary Fig. S11A), the massage group (MD, −6.00; 95% CI: −12.34 to 0.34) (Supplementary Fig. S11B), or the rocking group (MD, −0.43; 95% CI: −0.24 to 1.10)²⁵ (Supplementary Fig. S11C). The first cry duration was significantly higher in the feeding of breast milk group than in the 20% sucrose group (MD, 6.00; 95% CI: 2.50 to 9.50) (Supplementary Fig. S11D) or the NNS (pacifier) group (MD, 4.00; 95% CI: 0.18–7.82)²⁵ (Supplementary Fig. S11E).

Discussion

All studies included in this review evaluated the effects of breastfeeding or feeding of breast milk on the pain during a single blood sampling. Breastfeeding was associated with a reduction in pain scores (DAN, PIPP, N-PASS, NIPS, NFCS, and ALPS-Neo), the crying duration, and the first cry duration, when compared with nonintervention, placebo, mother's holding, breast milk odor, mother's heartbeat, music therapy, skin-to-skin, and EMLA ointment. Breastfeeding showed no advantages in reducing four types of pain scores (DAN, IBCS, N-PASS, and PIPP), heart rate change, and heart rate recovery time, when compared with higher concentrations of glucose/sucrose. However, it was more effective in reducing NIPS scores, oxygen saturation fluctuation, percentage of crying time, and duration of the first cry.

Based on the above results, we recommend that breastfeeding, or its alternatives (such as sucrose or glucose), should be provided to neonates undergoing a single blood sampling for relieving pain. Feeding of breast milk produced different results, suggesting that its efficacy in relieving pain is not well established. Its outcomes were only superior to those of the placebo (sterile water or distilled water), massage, or nonintervention. Nevertheless, in blood sampling, breastfeeding or feeding of breast milk could encourage mothers to breastfeed their babies, promote their bonding, and relieve the psychological burden on mothers.

Our recommendations may be applicable to a large population, because most full-term babies need venipuncture or heel puncture in the first few days of life. In many countries, all newborns undergo heel lance for metabolic screening in the first week of life. Even in countries where metabolic screening is not yet compulsory, healthy full-term newborns often need heel lance or venipuncture for other simple testings.²⁹ Therefore, our findings in this study have provided reliable advice for pain relief in children who require heel lance or venipuncture.

The eligible studies in this review only included healthy full-term neonates. However, a different population of infants, such as premature infants and sick full-term newborns, has to undergo repeated blood samplings during hospitalization.^30,31 The optimal analgesics for them have not yet been found. One trial³² reported that preterm infants (<31 weeks gestational age), who received repeated sucrose administration before painful procedures, exhibited poorer neurological development, compared with those receiving fewer sucrose doses. Therefore, breastfeeding or feeding of breast milk, due to their safety, may be introduced to replace sucrose.

Several limitations are evident in this review. First, there was heterogeneity in the tools used to evaluate pain across studies. This issue has also been encountered in a previous review on using sucrose to reduce procedural pain in neonates.¹¹ Various physiological, behavioral parameters, and pain scales were randomly chosen to assess pain in previous studies. A unified and reliable tool should be designed in the future. Second, we only analyzed the effects of breastfeeding or feeding of breast milk on the pain from a single blood sampling.

However, many preterm or sick full-term neonates experience repeated blood sampling during hospitalization. Therefore, future studies should focus on the effects of breastfeeding or feeding of breast milk on recurrent procedural pain. Moreover, it is imperative to clarify the long-term impact of repeated breastfeeding or feeding of breast milk on the acceptance of infants, especially preterm neonates, toward breastfeeding at a later stage. Only one study,¹² which assessed the maternal perception of sucking during breastfeeding after a single blood sampling, reported no significant changes in this acceptance.

However, the impact of repeated exposure remains to be further explored. Finally, the included studies demonstrated a marked heterogeneity in the duration and quantity of prior exposure to breastfeeding or feeding of breast milk, as well as control interventions.

Conclusion

Breastfeeding is recommended for alleviating procedural pain in full-term neonates undergoing a single blood sampling. Its effect is second only to that of glucose/sucrose (12.5%–30% concentration). Feeding of breast milk might not be as effective as breastfeeding or glucose/sucrose in reducing blood sampling pain in full-term neonates. The safety or effectiveness of breastfeeding or feeding of breast milk on the pain from repeated blood sampling remains uncertain, necessitating the conduction of better designed RCTs, particularly those based on preterm neonates.

Authors' Contribution

W.B.T., J.T., and C.P.S. contributed to the conception and design. C.P.S. and J.T. contributed to data acquisition or analysis and interpretation of data. C.P.S. and J.T. were involved in drafting the article. W.B.T. and W.L. revised the article critically for important intellectual content. All authors have given final approval for the version to be published.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

This study was funded by Nanjing special fund for health science and technology development (YKK21147).

Supplementary Material

References

Raja

, Carr

, Cohen

, et al. The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises. Pain, 2020; 161(9):1976–1982; doi: 10.1097/j.pain.0000000000001939

Perry

, Tan

, Chen

, et al. Neonatal Pain: Perceptions and current practice. Crit Care Nurs Clin North Am, 2018; 30(4):549–561; doi: 10.1016/j.cnc.2018.07.013

Maxwell

, Fraga

, Malavolta

. Assessment of pain in the newborn: An update. Clin Perinatol, 2019; 46(4):693–707; doi: 10.1016/j.clp.2019.08.005

Williams

, Lascelles

BDX

. Early neonatal pain-A review of clinical and experimental implications on painful conditions later in life. Front Pediatr, 2020; 8:30; doi: 10.3389/fped.2020.00030

Ohlsson

, Shah

. Paracetamol (acetaminophen) for prevention or treatment of pain in newborns. Cochrane Database Syst Rev, 2020; 1(1):Cd011219; doi: 10.1002/14651858.CD011219.pub4

Abdel Shaheed

, Ferreira

, Dmitritchenko

, et al. The efficacy and safety of paracetamol for pain relief: An overview of systematic reviews. Med J Aust, 2021; 214(7):324–331; doi: 10.5694/mja2.50992

Johnston

, Campbell-Yeo

, Disher

, et al. Skin-to-skin care for procedural pain in neonates. Cochrane Database Syst Rev, 2017; 2(2):Cd008435; doi: 10.1002/14651858.CD008435.pub3

Shah

, Herbozo

, Aliwalas

, et al. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database Syst Rev, 2012; 12(12):Cd004950; doi: 10.1002/14651858.CD004950.pub3

Pillai Riddell

, Racine

, Gennis

, et al. Non-pharmacological management of infant and young child procedural pain. Cochrane Database Syst Rev, 2015; 2015(12):CD006275; doi: 10.1002/14651858.CD006275.pub3

10.

García-Valdivieso

, Yáñez-Araque

, Moncunill-Martínez

, et al. Effect of non-pharmacological methods in the reduction of neonatal pain: Systematic review and meta-analysis. Int J Environ Res Public Health, 2023; 20(4):3226; doi: 10.3390/ijerph20043226

11.

Stevens

, Yamada

, Ohlsson

, et al. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev, 2016; 7(7):CD001069; doi: 10.1002/14651858.CD001069.pub5

12.

Carbajal

, Veerapen

, Couderc

, et al. Analgesic effect of breast feeding in term neonates: Randomised controlled trial. BMJ (Clinical research ed.), 2003; 326(7379):13; doi: 10.1136/bmj.326.7379.13

13.

Bilgen

, Ozek

, Cebeci

, et al. Comparison of sucrose, expressed breast milk, and breast-feeding on the neonatal response to heel prick. J Pain, 2001; 2(5):301–305; doi: 10.1054/jpai.2001.23140

14.

Codipietro

, Ceccarelli

, Ponzone

. Breastfeeding 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

15.

Obeidat

, Shuriquie

. Effect of breast-feeding and maternal holding in relieving painful responses in full-term neonates: A randomized clinical trial. J Perinat Neonatal Nurs, 2015; 29(3):248–254; doi: 10.1097/JPN.0000000000000121

16.

Chang

, Filoteo

, Nasr

. Comparing the analgesic effects of 4 nonpharmacologic interventions on term newborns undergoing heel lance: A randomized controlled trial. J Perinat Neonatal Nurs, 2020; 34(4):338–345; doi: 10.1097/JPN.0000000000000495

17.

Zhu

, Hong-Gu

, Zhou

, 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

18.

Chiabi

, Eloundou

, Mah

, et al. Evaluation of breastfeeding 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

19.

Soltani

, Zohoori

, Adineh

. Comparison the effectiveness of breastfeeding, oral 25% dextrose, kangaroo-mother care method, and EMLA cream on pain score level following heal pick sampling in newborns: A randomized clinical trial. Electron Physician, 2018; 10(5):6741–6748; doi: 10.19082/6741

20.

Leite

, Linhares

, Lander

, et al. Effects of breastfeeding on pain relief in full-term newborns. Clin J Pain, 2009; 25:827–832; doi: 10.1097/AJP.0b013e3181b51191

21.

Tavlar

, Karakoc

. The effect of breastfeeding, breast milk odour and mother's heartbeat sound on pain level in newborns: A randomized trial. Int J Nurs Pract, 2022; 28(6):e13067; doi: 10.1111/ijn.13067

22.

Upadhyay

, Aggarwal

, Narayanan

, et al. Antinociceptive effect of expressed breast milk in procedural pain in neonates: A randomized, placebo controlled, double blind trial. Pediatr Res, 2004; 53:120; doi: 10.1080/08035250410022792

23.

Uyan

, Ozek

, Bilgen

, et al. 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

24.

Ozdogan

, Akman

, Cebeci

, et al. 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

25.

Mathai

, Natrajan

, Rajalakshmi

. A comparative study of non-pharmacological methods to reduce pain in neonates. Indian Pediatr, 2006; 43(12):1070-1075.

26.

Yilmaz

, Arikan

. 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

27.

, Zhang

, Ding

, et al. Effect analysis of embracing breast milk sucking to relieve pain of neonatal heel blood sampling: A randomized controlled trial. Ann Palliat Med, 2021; 10(4):4384–4390; doi: 10.21037/apm-21-329

28.

Erdoğan Ç, Çamur

. The impact of breast milk taste and smell in reducing pain in infants undergoing blood drawing procedure: A randomized controlled study. Breastfeed Med, 2022; 17(8):673–677; doi: 10.1089/bfm.2022.0055

29.

Yavaş

, Bülbül

, Topçu Gavas

. The effect on pain level and comfort of foot massages given by mothers to newborns before heel lancing: Double-blind randomized controlled study. Jpn J Nurs Sci, 2021; 18(4):e12421; doi: 10.1111/jjns.12421

30.

Campbell-Yeo

, Eriksson

, Benoit

. Assessment and management of pain in preterm infants: A Practice Update. Children (Basel), 2022; 9(2):244; doi: 10.3390/children9020244

31.

Roofthooft

, Simons

, Anand

, et al. Eight years later, are we still hurting newborn infants?. Neonatology, 2014; 105(3):218–226; doi: 10.1159/000357207

32.

Johnston

, Filion

, Snider

, 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; doi: 10.1542/peds.110.3.523

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