Running head: BREAST MILK FOR PAIN RELIEF IN PRETERM INFANTS 1

Breast Milk for Pain Relief in Preterm Infants

Makeda de Comas

University of South Florida

BREAST MILK FOR PAIN RELIEF IN PRETERM INFANTS 2

Abstract

Clinical Problem: Within their first days of life, most infants undergo procedures known to be

painful. Frequent exposure to pain is known to be harmful to infants, so it is vital that pain is

effectively managed (Ou-Yang et al., 2013). Sugar solutions are frequently used to reduce pain

in neonates, but some research has shown possible long-term neurological effects when sugar

solutions are overused in preterm infants (Gao et al., 2016).

Objective: This synthesis discusses whether expressed breast milk (EBM) is as effective at

reducing pain in preterm infants as commonly used sugar solutions. Literature searches were

done using PubMed and CINAHL to collect Randomized Control Trials (RCTs) on the subject.

Key search terms used were preterm, neonates, infant, pain relief, analgesia, heel lance,

venipuncture, breast milk, expressed breast milk, sucralose and glucose.

Results: In preterm infants who receive EBM two minutes before a painful procedure there is an

equivalent reduction in pain in comparison to infants who receive sugar solutions two minutes

before a painful procedure. Collados-Gomez et al. (2017) showed in a randomized crossover trial

that EBM reduced pain as well as 24% sucrose during a venipuncture (p=0.28). Ou-Yang et al.

(2013) showed that EBM was as effective at reducing pain as 25% glucose during a heel-lance

procedure (p=0.38). Simonse et al. (2012) showed that EBM is as effective as 24% sucrose in

reducing pain after a heel-lance procedure (p=0.13). A Clinical Practice Guideline (CPG) advises

breast milk be used as a low-risk intervention for infant pain (Lago et al., 2009).

Conclusion: EBM was shown to give a statistically similar level of pain relief when compared to

sucrose/glucose in preterm infants. Further research should be conducted on the benefits of EBM

combined with other non-pharmacological forms of pain relief such as nonnutritive sucking,

facilitated tucking, and kangaroo care during painful procedures to increase pain relief.
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Breast Milk for Pain Relief in Preterm Infants

In many hospitals, it is the current standard of care to give infants sugar solution before

painful procedures to reduce infant pain. This is a widely-accepted method of reducing infant

pain, but it is not the only method (Collados-Gomez et al., 2017). Breast milk is recognized as

the only food source that infants should have for the first 6 months of life, and should be used

exclusively when available (Underwood, 2013). If it is possible to relieve pain with expressed

breast milk in premature infants, then this should be explored as a viable alternative.

Furthermore, the long-term safety of sugar solutions has not been conclusively decided (Gao et

al, 2016). A meta-analysis of RCTs showed that in preterm infants who received >10 doses of

sucrose within their first week had lower than average neurologic development compared to

preterm infants who received less doses (Gao et al., 2016). Until there is conclusive proof of the

long-term safety of sugar solutions, they should be used sparingly. Hesitation by some parents to

have sucralose given to their infants is possible, and in this case expressed breast milk should be

an option for these infants. Furthermore, although sugar solutions are widely available in U.S.

hospitals, they are not available in all health care location. EBM is free and allows parents a

chance to take part in their child’s care by providing breast milk. EBM is an effective option for

pain relief in preterm infants and should be offered when available.

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Literature Search

PubMed and CINAHL were used to search for RCTs on the topic of EBM for pain relief

in preterm infants. Key search terms used in this literature search were preterm, neonates, infant,

pain relief, analgesia, heel lance, venipuncture, breast milk, expressed breast milk, sucralose,

glucose. RCTs from the years 2012-2018 were included.

Literature Review

Three RCTs and an Italian CPG were used to support the hypothesis that EBM reduces

pain in preterm infants. The CPG outlined by Lago et al. (2009) states that painful stimuli in

neonates, especially preterm neonates, can lead to long-term effects on brain development. For

this reason, the CPG states that effective pain management is vital in preterm neonates. Notable

to the hypothesis, the guidelines state that breastfeeding and breast milk should be introduced 2

minutes prior to the painful procedure and, if possible, throughout the duration of the painful

procedure. The guidelines state that if oral sucrose or glucose is used in preterm infants, the

lowest effective concentration should be used due to the neurobehavioral effects seen in preterm

infants who receive >10 doses of high concentration (24-33%) sucralose within the first week of

life.

Collados-Gomez et al. (2017) compared the analgesic effects of EBM compared to 24%

oral sucrose on preterm neonates who underwent a venipuncture. This study was a randomized

noninferiority crossover trial of 64 infants who completed the trial. The study included 11 infants

born <28 weeks gestational age (classified as very preterm) and 53 infants born >28 weeks and

<37 weeks gestational age (classified as preterm) from 5 different NICUs. The 53 preterm

infants were randomly assigned to 2 groups of 27 (group one) and 26 (group two) infants and the

very preterm infants were randomly assigned to 2 groups of 6 (group three) and 5 (group four).
BREAST MILK FOR PAIN RELIEF IN PRETERM INFANTS 5

The infants in the group one and three received EBM during their first venipuncture and sucrose

during their second venipuncture. The infants in the group two and four received sucrose during

their first venipuncture and sucrose during their second. All participants weighed >2500g and

were born without congenital malformations. The study used the Premature Infant Pain Profile

(PIPP) to determine infant pain as well as the duration of the first cry. The results from the

infants born <28 weeks were examined separately from the results of infants born >28 weeks and

<37 weeks. In infants born <28 weeks, PIPP scores were 9 (9-14) with EBM and 4 (4-7) with

sucrose in the 11 infants <28 weeks. This is a statistically significant difference (p=0.009) and

shows that in early-preterm infants glucose relives pain to a greater extent than EBM does. PIPP

scores for the infants >28 weeks and <36 weeks were an average of 7 (4-9) with EBM and 6 (4-

8.25) with sucrose in late-preterm infants. There was not a statistically significant difference

between the intervention group and the control (p=0.28), which suggests that EBM is an

adequate pain reliever in comparison to 24% oral sucralose in late-term preterm infants. The

strengths of this study were in the crossover treatment of each infant with both EBM and

sucrose/glucose, the blinding of the participants and testers, the multiple hospital sites used in the

study, and that all enrolled infants completed the study. The weakness of this study is that there

were a small sample size of very preterm infants.

Ou-Yang et al. (2013) examined whether expressed breast milk (EBM) reduces

procedural pain associated with heel lancing in preterm neonates in comparison to both 25%

glucose solution and water. The study was a randomized control trial of 133 preterm infants and

used the Neonatal Pain Agitation and Sedation Scale (NPASS) and the duration of the first cry to

determine infant pain. Infants were included in the trial if they were born at <37 weeks gestation

and were <7 days of age at the time of the study. They were excluded for any congenital
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abnormalities or if their 5-minute Apgar score was <7. If they were crying for any reason <5

minutes before the scheduled heel lancing, they were excluded from the study as the study team

felt crying showed a sign of distress unrelated to the heel lancing. Infants were separated into

three groups and either given EBM (group one, 43 participants), 25% glucose (group two, 45

participants), or water (group three, 45 participants) 2 minutes before a heel lance procedure. The

NPASS and duration of first cry was measured directly after. This study showed no statistically

significant difference in pain scoring between infants who received EBM and the control group

who received sucrose (p=0.38). This suggests that EBM is a suitable alternative to sucrose for

pain relief in preterm infants. The strengths of this study are the number of enrolled infants, the

blinding of testers measuring the NPASS, and the standardized qualifications for inclusion in the

study. The weaknesses of the trial are that three infants were excluded from group one for a loss

of collection data and that duration of first cry is acknowledged by the authors to be an

ineffective measurement of pain.

Simonse et al. (2012) examined whether expressed breast milk (EBM) has a better

analgesic effect than 24% sucrose in preterm newborns. The study was a randomized controlled

trial and used the PIPP to measure infant pain after a heel-lance procedure. The study involved

71 infants with a gestation age >32 weeks and <37 weeks at birth. The infants were not included

in the study if they had an Apgar score <7 at 5 minutes, any major malformations, needed

ventilation assistance, drug withdrawal, or received analgesics or sedatives previously. The

participants were required to be exclusively breastfed prior to the trial. The infants in the study

were randomly assigned to three groups and assigned to receive either breastfeeding (group one,

23 participants), EBM (group two, 23 participants), or 24% sucrose (group three, 25 participants)

2 minutes before a heel-lance procedure. The average PIPP score for infants who received
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sucrose was 5.5 and 6.1 for those who received breastfeeding or EBM was 6.1. The score for the

breastfed group and the EBM group were not scored separately. There was not a statistically

significant difference in pain scoring between the breast milk group and the sucralose group

(p=0.13). This shows that EBM is a suitable option for pain relief in preterm infants born

between 32-37 weeks. The strengths of this study are that the groups were randomized and

blinded, the trial was conducted over multiple sites, and that all participants completed the trial.

The weakness of this study is that the breast-fed and infants who were given EBM were

combined into one group which did not take into consideration additional comfort which may

come from breastfeeding.

Synthesis

Collados-Gomez et al. (2017) showed in a randomized crossover trial that EBM reduced

pain as well as 24% sucrose during a venipuncture (p=0.28). Ou-Yang et al. (2013) showed in

their RCT that EBM was as effective at reducing pain as 25% glucose during a heel-lance

procedure (p=0.38). In the Simonse et al. (2012) RCT, EBM was determined as effective as 24%

sucrose in reducing pain after a heel-lance procedure (p=0.13).

The major weakness in each study is the reliance on the PIPP and NPASS scores to

determine infant pain level. Although these have been determined to be reliable methods of

determining infant pain when performed by a trained professional, pain is a subjective

measurement. These studies along with the CPG determine that EBM is as effective as sugar

solutions, though more research needs to be done to determine whether the analgesic effects of

EBM can be improved in conjunction with other non-pharmacological methods.

Clinical Recommendations
BREAST MILK FOR PAIN RELIEF IN PRETERM INFANTS 8

Based on this research, it is determined that EBM is an effective method of pain control

in preterm infants in comparison to placebo. It can also be determined that EBM is as effective as

sucrose/glucose solutions in reducing infant pain when given 2 minutes before blood-drawing

procedures. Furthermore, Italian CPG recommend breastfeeding during painful procedures, or

delivering EBM 2 minutes prior to procedures when the option is available (Lago et al., 2009).

Because there are potential complications from using high concentration sucrose/glucose

overtime in preterm infants, research into alternative methods of pain relief is important.

Compared to sucrose and glucose solutions, EBM is a low-risk method of pain relief (Gao et al.,

2016.)
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References

Collados-Gomez, L., Ferrera-Camacho, P., Fernandez-Serrano, E., Camacho-Vicente, V., Flores-

Herrero, C., Garcia-Pozo, A. & Jimenez-Garcia, R. (2017). Randomized crossover trial

showed that using breast milk or sucrose provided the same analgesic effect in preterm

infants of at least 28 weeks. Acta Paediatrica, 107(3), 436-441.

http://doi.org/10.1111/apa.14151

Gao, H., Gao, H., Xu, G., Li, M., Du, S., Li, F., Zhang, H., & Wang, D. (2016). Efficacy and

safety of repeated oral sucrose for repeated procedural pain in neonates: A systematic

review. International Journal of Nursing Studies, 62, 118-125.

http://doi.org/10.1016/j.ijnurstu.2016.07.015

Lago, P., Garetti, E., Merazzi, D., Pieragostini, L., Ancora, G., Pirelli, A., & Bellieni, C. (2009).

Guidelines for procedural pain in the newborn. Acta Paediatrica, 98(6), 932-939.

http://doi.org/ 10.1111/j.1651-2227.2009.01291.x

Ou-Yang, M., Chen, I., Chen, C., Chung, M., Chen, F. & Huang, H. (2013). Expressed breast

milk for procedural pain in preterm neonates: A randomized, double-blind, placebo-

controlled trial. Acta Paediatrica, 102(1), 15-21. http://doi.org/ 10.1111/apa.12045

Simonse, E., Mulder, P. & Van Beek, R. (2012). Analgesic effect of breast milk versus sucrose

for analgesia during heel lance in late preterm infants. Pediatrics, 129(4), 857-863.

http://doi.org/10.1542/peds.2011-2173

Underwood, M. (2014). Human milk for the premature infant. Pediatric clinics of North

America, 60(10), 189-207. http://doi.org/10.1016/j.pcl.2012.09.008

BREAST MILK FOR PAIN RELIEF IN PRETERM INFANTS 10

To explore if breast milk is an eligible option for pain relief in preterm infants it must be

determined how EBM compares to sugar solution in reducing infant pain level during the 5

minutes following blood-drawing procedures. The expected outcome measure is decreased pain

in infants who receive breast milk in comparison to placebo, and statistically equivalent reaction

to breast milk and sucralose. Expressed breast milk was compared to sugar solutions because of

the ability to double-blind the procedure, which is not as easily facilitated when breastfeeding is

compared to sweet solutions.