Non-pharmacological methods for pain relief in newborns: an integrative literature review

Non-pharmacological methods for pain relief in newborns: an integrative literature review

Métodos não farmacológicos para o alívio da dor no recém-nascido: revisão integrativa da literatura

ABSTRACT

Objective: to synthesize knowledge about the use of non-pharmacological methods to relieve pain in newborns. Method: this is an integrative literature review, carried out in the Latin American and Caribbean Literature in Health Sciences, Nursing Database and Spanish Bibliographic Index in Health Sciences, via the Virtual Health Library, MEDLINE (Literature International Health Sciences), via PubMed, Scopus and Web of Science databases. Results: fifty-six articles were included, the majority of which were developed in Turkey between 1995 and 2022. Twenty non-pharmacological methods used to manage pain in newborns undergoing painful procedures were highlighted, which were applied alone or in combination, standing out in terms of effect or effectiveness are sweet solutions and breastfeeding. Conclusion: most of the methods identified were able to reduce newborn pain and crying during and after painful procedures.

Descriptors: Newborn; Methods; Pain Management; Cry; Evidence-Based Clinical Practice.

RESUMO

Objetivo: mapear a literatura a respeito da produção de tecnologias educacionais voltadas aos professores da educação infantil, sobre o manejo de acidente com pré-escolares. Método: protocolo de revisão de escopo conduzida a partir da metodologia do Joanna Briggs Institute. Os achados serão reportados utilizando a extensão do checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. O protocolo está na Open Science Framework. A questão norteadora foi elaborada com base no mnemônico PCC: População, Conceito e Contexto. Foram utilizadas como bases para a pesquisa: MEDLINE/PubMed, Embase, Scopus, Web of Science, CINAHL-EBSCO e Google Scholar. As referências dos estudos primários serão consultadas como estratégias adicionais. Serão considerados elegíveis os estudos que estejam dentro dos critérios estabelecidos, e que respondam à pergunta de pesquisa. A seleção ocorrerá de maneira independente por dois revisores, utilizando os programas EndNote® e Rayyan®, obedecendo os critérios de elegibilidade, e as divergências serão discutidas por um terceiro revisor. Para a síntese e a extração dos dados será considerado um formulário elaborado pelos autores. Os resultados serão apresentados por meio de quadro, fluxograma e discussão narrativa.

Descritores: Professores Escolares; Tecnologias Educacionais; Primeiros Socorros; Educação em Saúde; Revisão de Escopo.

INTRODUCTION

Pain can be defined as an unpleasant sensory and emotional experience related to or analogous to actual or potential tissue damage.¹ When it occurs in the first 28 days of life, it is called neonatal pain.² For a long time, the hypothesis remained that newborns (NBs) do not feel pain in the same way as older children and adults. Based on these beliefs, until the end of the 1980s, it was common to perform surgeries on this group of children without using adequate methods for pain relief.³

Currently, it appears that NBs not only feel pain, but also, due to their immature nervous system, are hypersensitive to painful stimuli.⁴ When pain is inadequately treated during the neonatal period, persistent effects may occur,⁵ such as the development of hypersensitivity to pain and altered neurodevelopment.⁶ For this reason, neonatal pain assessment and management should be encouraged to enable the development of individualized treatment plans.⁴

Pharmacological and non-pharmacological methods are options to reduce the negative impact of pain and agitation in NBs, with concerns emerging about the adverse effects of analgesia and sedatives.⁷ In this context, non-pharmacological pain management (proximal, distal and procedural) demonstrated effectiveness in reducing painful responses in NBs⁶ and the ability to reduce dosage or exclude the use of drugs.⁸

Numerous non-pharmacological methods (NPMs) have been studied and applied to avoid or reduce pain during procedures in children, highlighting distraction maneuvers, tactile stimulation, skin-to-skin contact (SSC), non-nutritive sucking (NNS), offering breast milk (BM), sweet solutions (25% glucose) and breastfeeding.⁴

Considering that acute pain management must be one of the priorities for healthcare professionals who care for childhood patients⁹ and who, constantly, new non-pharmacological interventions have been developed with the aim of avoiding or mitigating pain in NBs who are subjected to routine painful procedures (such as vaccine administration and heel prick tests) or those related to the need for hospitalization,¹⁰ the guiding research question emerged: what are the NPMs for pain relief in NBs?

OBJECTIVE

To synthesize knowledge about the use of NPM to relieve pain in NBs.

METHOD

This is an integrative literature review (ILR), whose methodological path was guided by five phases: problem identification/formulation; literature search/data collection; data assessment; analysis of the findings of the articles included in the review; and presentation and interpretation of results.¹¹

In the first stage, the research question was formulated based on the PICo strategy, in which P corresponds to Participant (NB); I corresponds to the phenomenon of Interest (methods); and Co corresponds to Context of study (pain management). Therefore, the following guiding question was created: what are the NPMs for pain relief in NBs?

Subsequently, controlled and uncontrolled descriptors were established, selected after consulting the Descriptors in Health Sciences (DeCS) and the Medical Subject Headings (MeSH). These terms were crossed using the Boolean operators AND and OR (Chart 1).

Chart 1. Research question stratification following the PICo strategy. Teresina, Piauí, Brazil, 2023

PICo strategy
Description	Acronym	Components	Descriptors	Uncontrolled descriptors
Participants	P	NB	Recém-Nascido Infant, Newborn
Phenomenon of interest	I	NPM	Métodos Methods	Non-Pharmacological Methods
Context of study	Co	Pain management	Manejo da Dor Pain Management

Source: own elaboration.

Primary studies that address NPMs for pain relief in full-term NBs, published in English, Portuguese or Spanish, were included. Narrative literature review studies/traditional, systematic or integrative review, notes, editorials, reports, dissertations and theses, studies that included other age groups, in which it was not possible to establish the methods used only for the group of newborn children, were excluded. It is emphasized that no time frame was used to select the articles, as a broad approach was aimed.

Literature search took place between August 2022 and January 2023, simultaneously, by two researchers in databases accessed through the Coordination for the Improvement of Higher Education Personnel (CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) Journal Portal in an area with recognized Internet Protocol (IP). The databases researched were Latin American and Caribbean Literature in Health Sciences (LILACS), Nursing Database (BDENF) and Índice Bibliográfico Español en Ciencias de la Salud (IBECS), via Virtual Health Library (VHL), MEDLINE (International Literature in Health Sciences), via PubMed, in addition to Scopus and Web of Science (Chart 2).

Chart 2. Crossings of descriptors used by database in data search. Teresina, Piauí, Brazil, 2023

Database	Strategy
LILACS/BDENF/IBECS - via VHL	("Infant, Newborn") AND (methods) OR ("Non-pharmacological methods") AND ("Pain Management")
MEDLINE - via PubMed	(("Infant, Newborn") AND ((Methods) OR ("Non-pharmacological methods"))) AND ("Pain Management")
Scopus	(TITLE-ABS-KEY ("Infant, Newborn") AND TITLE-ABS-KEY (methods) OR TITLE-ABS-KEY ("Non-pharmacological methods") AND TITLE-ABS-KEY ("Pain Management"))
Web of Science	"Infant, Newborn" (All Fields) and Methods (All Fields) or "Non-pharmacological methods" (All Fields) and "Pain Management" (All Fields)

Source: own elaboration.

Initially, identified citations were imported into the EndNote basic Reference Manager, where duplicates were identified and removed. Soon after, articles were selected by reading titles and abstracts based on the inclusion criteria presented previously. In selected studies considered potentially eligible, they were read in full, which determined the final sample of this ILR, which followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Forthwith, data was collected using a form adapted from Ursi (2006), which was able to ensure that all relevant data was extracted. The following data was included: country/year; objectives; design/number of participants; interventions identified; effect; results.

To assess the extracted data, the JBI was followed, according to which the levels of evidence, according to study design, are: level I – evidence obtained from a systematic review containing only randomized controlled clinical trials; level II – evidence obtained from at least one randomized controlled clinical trial; level III. 1 – evidence obtained from well-designed controlled clinical trials, without randomization; level III. 2 – evidence obtained from well-designed cohort or case-control studies, analytical studies, preferably from more than one center or research group; level III. 3 – evidence obtained from multiple time series, with or without intervention and dramatic results in uncontrolled experiments; level IV – opinion from respected authorities, based on clinical criteria and experience, descriptive studies or reports from expert committees.¹²

For the results produced, the data collection instruments were organized and then typed into Microsoft Excel version 2010 spreadsheet. The data obtained through analysis of the objectives, results and conclusion of each study were grouped by similarity and organized into thematic categories.¹³

RESULTS

A total of 2,722 potentially relevant articles for the review were identified (MEDLINE via PubMed n= 1,208; LILACS/BDENF/IBECS via VHL n = 27; Web of Science n = 808; Scopus n= 679), of which 124 were selected for full reading, leaving a total of 61 articles, which met the inclusion criteria (MEDLINE via PubMed n = 27; LILACS/BDENF/IBECS via VHL n = 2; Web of Science n = 1; Scopus n= 31) and who were selected to compose the sample, as illustrated in Figure 1.

Figure 1. Study selection flowchart according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020). Teresina, Piauí, Brazil, 2023

Source: own elaboration.

As for the country, the majority of studies were developed in Turkey (19), followed by the United States of America (USA) (7), China (5) and Brazil (4), between 1995 and 2024, with the largest number published in 2015 (9) and 2021 (9), followed by 2022 (7). With regard to the number of participants, significant variability was identified, with research involving between 29 and 671 NBs. In relation to study design, randomized clinical trials prevailed, with a larger quantity presenting level of evidence II (45), which demonstrates the suitability for assessing the effect and effectiveness of interventions (Chart 3).

There were 20 NPMs used to manage the pain of NBs undergoing painful procedures, which were applied alone or associated to compare the effect/efficacy between them and/or the control group (CG), namely: oral sweet solution administration (21), including sucrose (11), glucose (8) and dextrose (2), in different concentrations; breastfeeding (11); NNS (8); Kangaroo Mother Care (KMC) and SSC (9); administration of milked BM (7); swaddling (7); olfactory stimulus (5); auditory stimulus (3); music therapy (2); mechanical vibration application (2); acupuncture (2) and its variation, acupressure (2); massage (2); containment (1); cuddling position (1); radiant heat (1); crochet octopus (1); Yakson method (1); and massage (1). Regarding the effect or effectiveness of interventions, it was found that the use of sweet solutions and breastfeeding stand out as non-pharmacological measures in reducing pain in NBs (Chart 3).

When analyzing the literature on the topic, original studies aim at an interest in diverse NPMs, which will be discussed below, through comparisons of different studies and their results. The first category includes articles that describe oral sweet solution administration. The second focused on breastfeeding as a possibility for intervention. The third discusses the use of NNS. The fourth refers to KMC and SSC. Finally, the fifth category refers to swaddling.

Chart 3. Characterization of selected studies in chronological order according to code, country, year, number of participants, level of evidence, objectives, study design, identified interventions, effect/results. Teresina, Piauí, Brazil, 2023

C¹	Country/ year/ number of p²/ LoE³	Objectives/ design	Interventions identified	Effect/results
A1¹⁴	England/ 1995/ 60 NBs/ II	Assess the effects of different concentrations of sucrose on neonatal pain measures. Randomized, double-blind, controlled study	Different concentrations of oral glucose.	Significant reduction in overall crying time and heart rate (HR) after three minutes in NBs who received 50% sucrose, compared to controls.
A2¹⁵	United States of America/ 2002/ 84 NBs/ III.2	Examine the effectiveness of pacifiers and sugar alone and in combination in controlling pain in NBs. Experimental design	NNS with and without sucrose.	The sugar-coated pacifier group had significantly shorter crying durations than the water-moistened pacifier and CGs.
A3¹⁶	Turkey/ 2004/ 60 NBs/ II	Assess the analgesic effect of spray glucose. Randomized, masked, placebo-controlled, crossover study	30% glucose by syringe or oral spray.	Pain scores were significantly lower in the 30% glucose groups administered by spray or syringe compared with the placebo group.
A4¹⁷	Turkey/2005/ 62 NBs/ II	Compare the effect of foremilk, hindmilk and sterile water on reducing pain in NBs undergoing minor painful procedures. Randomized clinical trial	Foremilk, hindmilk or sterile water.	No statistically significant differences were found between the three.
A5¹⁸	Turkey/2007/ 102 NBs/ III.2	Examine and compare the analgesic effects of breastfeeding and sucrose solutions in reducing pain due to venipuncture in full-term NBs. Control case study	Breastfeeding and use of oral sucrose solutions.	Crying time was shorter for both sucrose and breastfeeding than in the CG.
A6¹⁹	South Korea/ 2008/ 99 NBs/ III.2	Test the effect of Yakson (traditional Korean touch method) and NNS in reducing pain in NBs undergoing the heel puncture procedure. Control case study	Yakson and NNS method.	Oxygen saturation levels in infants in the Yakson and NNS groups were significantly better than in infants in the CG.
A7²⁰	Spain/2008/ 150 NBs/ III.2	Assess pain in healthy NBs who require blood testing for a heel puncture procedure and compare different pain management methods. Control case study	Containment mechanisms, NNS and sucrose.	In the CG, the mean score on the discomfort scale was 3.92, with moderate pain; the group that received NNS-placebo had a score of 2.1, mild pain; the group that received NNS-sucrose obtained 1.5 points, mild pain.
A8 ²¹	Italy/ 2008/ 101 NBs/ II	Compare the effectiveness of breastfeeding versus orally administered sucrose solution in reducing pain response during plantar puncture blood collection. Open, randomized and controlled study	Breastfeeding and oral sucrose solution.	NBs’ median pain profile scores were lower in the breastfeeding group (3.0) than in the sucrose solution group (8.5).
A9 ²²	Brazil/ 2009/ 640 NBs/ II	Compare the efficacy of oral treatment with 25% dextrose and/or SSC for analgesia in full-term NBs during intramuscular injection of hepatitis B vaccine. Prospective, randomized, partially blind clinical trial	25% oral dextrose and SSC.	The use of oral treatment with 25% dextrose reduced procedural pain duration. SSC decreased pain and injection duration. The combination of the two analgesic measures was more effective than either measure alone.
A10²³	Taiwan/ 2010/ 105 NBs/ II	Compare the effectiveness of NNS and glucose solution as pain relief interventions in infants undergoing venipuncture procedures. Randomized, controlled study	NNS and glucose solution diluted with 25% oral sterile water.	Both the NNS and glucose solution groups had significantly lower pain scores than the CG.
A11²⁴	Belgium/ 2010/ 304 NBs/ II	Investigate which glucose concentration is most effective in reducing pain during venipuncture in NBs. Double-blind clinical trial	Different concentrations of oral glucose.	The mean pain score was significantly lower in the 30% glucose group (3.99) when compared with the placebo group (8.43).
A12²⁵	Turkey/ 2011/ 120 NBs/ II	Compare the effects of using BM, sucrose and pacifiers to overcome pain during painful interventions for NBs on crying time and pain. Prospective, randomized and controlled study	SNN, oral sucrose and BM.	Sucrose followed by a pacifier was the most effective method to reduce NBs’ crying time.
A13 ²⁶	Canada/ 2011/ 330 NBs/ II	Determine the relative efficacy of liposomal lidocaine, sucrose and their combination in reducing pain in full-term NBs. Double-blind, randomized, controlled, double-dummy study	Before venipuncture for the NB screening test, infants received (1) 1 g of liposomal lidocaine cream topically, (2) 2 mL of 24% oral sucrose solution, or (3) sucrose and liposomal lidocaine.	Sucrose was more effective than liposomal lidocaine in reducing pain during venipuncture in NBs. The addition of liposomal lidocaine to sucrose did not confer any additional benefit to sucrose alone. There was no evidence of harm from liposomal lidocaine or sucrose.
A14²⁷	United States of America/2013/ 30 NBs/II	Test the hypothesis that SSC would reduce the pain of hepatitis B vaccine injection in full-term NBs. Randomized controlled trial	SSC.	SSC infants cried less compared to CGs (23 versus 32 seconds during injection; 16 versus 72 seconds during recovery).
A15²⁸	Iran/2013/ 135 NBs/ III.2	Assess the effect of a familiar non-maternal scent on neonatal pain responses. Experimental clinical trial	Olfactory stimulus of 0.64 g of vanillin diluted in 100 ml of 85% glycerol.	Crying duration in the familiar smell group was significantly shorter than in the other two.
A16²⁹	Estonia/ 2014/ 69 NBs/ III.2	Assess the impact of vanilla on infants’ responses to a painful toe prick, including possible gender differences. Case control study	Olfactory stimulation with vanilla aroma oil.	Vanilla exposure had no significant effect on any of the behavioral measures.
A17³⁰	Turkey/ 2015/ 42 NBs/ II	Investigate the effect of laser acupuncture on the Yintang point before heel puncture as a non-pharmacological intervention for pain treatment in NBs. Randomized clinical trial	Laser acupuncture.	The mean procedure time was significantly shorter in the laser acupuncture group, however the mean crying time was longer and the Neonatal Infant Pain Scale (NIPS) score was lower compared to the oral sucrose group.
A18³¹	Iran/2015/ 30 NBs/ III.2	Determine the effect of familiar auditory stimuli on pain induced by arterial blood sampling in full-term NBs. Case control study	Familiar auditory stimuli in pain.	The findings showed significant differences between the control and test groups, indicating the effect of mothers’ voice in reducing infants’ pain during arterial blood sampling.
A19³²	India/2015 180 NBs/ II	Assess and compare the effectiveness of the combination of sucrose and NNS for analgesia in NBs undergoing heel puncture. Randomized control clinical trial	30% oral sucrose and NNS.	The median pain scale score was 3 in the group receiving sucrose administration associated with NNS compared to 7 in the group receiving sucrose alone, 9 in the group receiving NNS and 13 in the CG.
A20³³	China/2015/ 40 NBs/ II	Investigate the effects of SSC on HR, transcutaneous oxygen saturation, facial expressions, physical activity and sound performance of infants. Randomized clinical trial	SSC.	In the seven periods during puncture, ten seconds after the start and ten seconds after the end, the neonatal HRs of the two groups changed.
A21³⁴	United States of America/2015/ 56 NBs/ II	Assess the effect of oral sucrose on skin blood flow (SBF), perfusion units, measured by Laser Doppler Imager (LDI) in full-term NBs, and pain response (NIPS score) during heel puncture. Double-blind, placebo-controlled study	24% oral sucrose sterile water.	The mean SBF and median NIPS scores immediately after heel puncture were lower in NBs treated with sucrose.
A22³⁵	China/ 2015/ 671 NBs/ II	Study the effects of NNS and swaddling on NBs’ behavioral and physiological parameters during shallow or deep heel puncture procedures. Prospective, multicenter, randomized, controlled clinical trial	NNS and swaddling.	A significant synergistic analgesic effect was observed between the swaddling and NNS groups in both the superficial (F = 5.952, p = 0.015) and deep (F = 7.452, p = 0.007) procedures. The NNS group showed the lowest pain score.
A23³⁶	Turkey/ 2015/ 60 NBs/ II	Assess NBs’ pain perception during hepatitis B vaccination performed in the facilitated cuddling position and in the classic holding position, respectively. Randomized controlled experimental study	Easy cuddling position and classic containment position.	The mean pain scores of NBs vaccinated in the facilitated cuddling position (2.83 ± 1.18) were statistically and significantly lower than the scores of NBs vaccinated in the classic containment position (6.47 ± 1.07) (p < 0.05).
A24³⁷	United States of America/2015/ 29 NBs/ II	Examine the analgesic effect of sucrose combined with radiant heat compared to sucrose taste alone during a painful procedure in healthy full-term NBs. Randomized and controlled study	Oral sucrose combined with radiant heat and sucrose alone.	The sucrose combined with heat group cried and grimaced for 50% less time after vaccination than the sucrose group alone (p < 0.05).
A25³⁸	China/2015/ 250 NBs/ II	Test the effectiveness of breastfeeding, music therapy and the combination of breastfeeding and music therapy in relieving pain in healthy NBs during heel puncture. Randomized controlled trial	Breastfeeding and music therapy.	NBs in breastfeeding and combined breastfeeding + music therapy groups had significantly longer latency to the first cry, shorter duration of the first cry and lower mean pain scores during and one minute after heel puncture compared to the other two groups.
A26³⁹	Iran/ 2016/ 120 NBs/ III.1	Compare the analgesic effect of KMC, breastfeeding and swaddling on Bacillus Calmette-Guerin (BCG) vaccination in full-term NBs. Randomized study	Breastfeeding and KMC.	Breastfeeding was more effective than KMC and swaddling in reducing pain.
A27⁴⁰	United States of America/ 2016/ 56 NBs/ II	Determine mechanical vibration safety and effectiveness for relieving heel puncture pain in infants. Parallel design randomized controlled study	24% oral sucrose and mechanical vibration.	Infants in the vibration group had significantly lower scores and more stable HR during heel puncture (p = 0.006, p = 0.037) and two minutes after heel puncture (p = 0.002, p = 0.016) than those in the no vibration group.
A28⁴¹	Brazil/ 2016/ 11 nurses/ IV	Describe nursing team practices in managing pain in NBs undergoing peripherally inserted central catheter insertion in a Neonatal Intensive Care Unit (NICU). Descriptive, exploratory study with a qualitative approach	Description by the nursing team of the non-pharmacological practices most used in the NICU.	The nursing team considers the use of non-pharmacological practices to be effective, isolated or associated with pharmacological practices. NNS, 25% oral glucose and swaddling are considered safe, effective and adaptable analgesic practices for services.
A29 ⁴²	South Korea/ 2016/ 56 NBs/ II	Investigate the effectiveness of KMC as a pain relief intervention in infants in South Korea. Clinical trial	KMC.	The HR of infants with KMC was lower at one and two minutes after sampling than in the CG. The pain scores of infants with KMC were significantly lower during and after sampling. Crying duration of infants with KMC was around 10% of the duration of the CG.
A30⁴³	Turkey/ 2017/ 74 NBs/ II	Determine the effect of swaddling on pain, vital signs and duration of crying during heel puncture in NBs. Randomized controlled study	Swaddling.	The mean pain of NBs swaddled during and after the procedure was lower than that of NBs not swaddled (p < 0.05). Furthermore, the crying duration of swaddled NBs was shorter than that of those not swaddled (p < 0.05).
A31⁴⁴	Pakistan/ 2017/ 252 NBs/ II	Know neonatal pain, its score and the effectiveness of oral dextrose in managing neonatal pain. Randomized control study	10% oral dextrose.	The mean pain score with 10% dextrose and sterile water was 4.31 and 6.26, respectively, and the difference between the two was statistically significant.
A32⁴⁵	Italy/ 2017/ 80 NBs/ II	Assess the differential effect of oral solutions (glucose, BM) provided alone or combined with the mother-NB relationship (safety, breastfeeding). Randomized clinical trial	Bolus of 2 mL of 20% oral glucose solution and bolus of 2 mL of oral BM.	Oral glucose alone or combined with maternal retention was associated with no cortical activation during heel puncture. Milked BM was associated with bilateral activation located in the somatosensory and motor cortices (p < 0.01). Breastfeeding was associated with extensive bilateral activation of the somatomotor, somatosensory and right parietal cortices (p < 0.01).
A33⁴⁶	India/ 2018/ 61 NBs/ II	Assess the effectiveness of KMC in relieving pain associated with vaccination in infants ≤14 weeks postoperatively. Randomized controlled study	KMC.	Post-vaccination pain and crying duration were significantly lower in infants who received KMC.
A34⁴⁷	United States of America/ 2018/ 33 NBs/ II	Determine which intervention could decrease pain response in infants undergoing Ponseti casting for idiopathic clubfoot. Double-blind randomized controlled trial	20% oral sucrose solution (S), water (W) or milk (M) in a bottle (breast or not).	During casting, the mean NIPS score for milk, 0.91 (SD=1.26, p = 0.0005), and sucrose, 0.64 (SD=1.27, p < 0.0001), was significantly lower than for water, 2.27 (SD=2.03), but not different from each other (p = 0.33). After casting, sucrose’s NIPS score, 0.69 (SD=1.53), continued to be significantly lower than that of milk, 2.11 (SD=2.37, p = 0.0065).
A35⁴⁸	Brazil/ 2019/ 50 NBs/ IV	Describe and quantify the pharmacological and non-pharmacological strategies used to relieve pain/stress in NBs during hospitalization in neonatal units. Quantitative, descriptive longitudinal study	Description of 11,722 interventions for pain treatment and control.	A total of 9,948 painful/stressful procedures were recorded, with a mean of 11.25 (± 6.3) per day per infant. A total of 11,722 interventions for pain management and relief were recorded, of which 11,495 (98.1%) were non-pharmacological strategies and 227 (1.9%) pharmacological strategies.
A36⁴⁹	Turkey/2019/ 139 NBs/ II	Determine the effects of foot massage and acupressure on pain during heel puncture in infants. Randomized clinical trial	Acupressure and massage.	There were statistically significant differences between acupressure, massage and CGs regarding pain reduction (4.30 ± 2.25, 3.95 ± 2.63, 6.04 ± 1.26, respectively).
A37⁵⁰	Pakistan/ 2019/ 60 NBs/ II	Test the hypothesis that breastfeeding is a good analgesia in NBs undergoing BCG vaccination. Randomized clinical trial	Breastfeeding.	In the experimental group, the mean crying duration was 16.48 seconds, while in the CG it was 34.93 seconds.
A38⁵¹	Italy/ 2019/ 56 NBs/ II	Investigate, using the skin conductance algesimeter (SCA) pain monitor index, the effects of 24% sucrose solution on pain perception during capillary and arterial blood sampling. Prospective randomized controlled study	24% oral sucrose.	SCA showed that the measurement of pain spikes per second during and three minutes after the procedures was lower in the sucrose group than in the placebo group and that this difference was statistically significant (p < 0.05).
A39⁵²	Iran/ 2019/ 120 NBs/ II	Assess the effectiveness of familiar olfactory stimulation with lavender aroma and glucose on blood collection pain in full-term infants. Randomized, single-blind clinical trial	Olfactory stimulus with lavender scent and 30% edible glucose orally.	Mean pain scores were 4.47 ± 1.81, 4.80 ± 1.92 and 5.97 ± 1.94 in the aromatherapy group, glucose group and CG, respectively (p < 0.001).
A40⁵³	Indonesia/2020/ 108 NBs/ II	Compare the analgesic effects of sensory stimulation (SS) with sucrose (SSS), SS with BM (SSBM) and oral sucrose alone (24%) in NBs undergoing venipuncture. Randomized and controlled clinical trial	SSS, SSBM, and sensory stimulation with oral sucrose alone (24%).	SSBM and SSS were more effective than oral sucrose alone (24%) (p = 0.001). No difference was observed between SSBM and SSS (p = 0.669).
A41⁵⁴	Vietnan/ 2020/ 42 NBs/ II	Assess the analgesic effect and safety of NNS in healthy full-term NBs during the heel prick test, using the Neonatal Pain Agitation and Sedation Scale (N-PASS). Randomized controlled study	NNS with silicone pacifier.	Mean pain scores at 30, 60, 90 and 120 seconds after heel prick were significantly lower in the NNS group than in the CG (4.73 ± 2.78 versus 7.90 ± 1.52 (p = 0 .0002); 3.64 ± 3.06 versus 5.55 ± 2.95 (p = 0.052); 2.59 ± 3.08 versus 5.25 ± 3.51 (p = 0.011); and 2.05 ± 2.94 versus 4.90 ± 3.99 (p = 0.013), respectively).
A42⁵⁵	Turkey/ 2020/ 160 NBs/ II	Experimentally determine the effects of three different methods (swaddling; swaddling and holding; swaddling, holding and breastfeeding) used during heel puncture on pain levels in healthy full-term NBs. Prospective, randomized and controlled study	Swaddling and breastfeeding.	The procedural pain scores in the CG were higher than in the swaddling group, swaddling + holding group and swaddling + holding + breastfeeding group.
A43⁵⁶	United States of America/ 2020/ 226 NBs/ III.1	Compare the analgesic effect of four non-pharmacological interventions (breastfeeding, oral sucrose, NNS and SSC) in full-term NBs between 24 and 48 hours of age undergoing heel puncture. Randomized study	Breastfeeding, oral sucrose administration, NNS and SSC.	The results indicate that all intervention groups showed a decrease in pain levels when compared to the CG (p <0.01). The oral sucrose group experienced a superior analgesic effect when compared with the SSC group (p < 0.01), but no difference was observed when compared with the breastfeeding group (p > 0.05) or the NNS group (p > 0.05).
A44⁵⁷	Turkey/2021/ 63 NBs/ III.2	Investigate the effect of acupressure applied to acupuncture points UB60 and K3 UB60 (hollow area between the edge of the external malleus and the calcaneus/Achilles tendon) and K3 (medial side of the foot, dorsum of medial malleolus and the hollow area between the edge of the Achilles tendon and the medial malleolus), in order to alleviate heel puncture pain in full-term NBs. Quasi-experimental study	Acupressure.	It was found that there was a significant difference between the groups regarding the mean scores on the Infant Neonatal Pain Scale during (p = 0.001) and after the procedure (p < 0.05), and the difference was found in favor of the acupressure group.
A45⁵⁸	Turkey/2021/ 140 NBs/ III.2	Investigate the effect of breastfeeding, kangaroo care and facilitating swaddling positioning on heel puncture pain in infants. Quasi-experimental study	Breastfeeding, KMC and facilitated swaddling position.	The facilitated folding position group cried less and experienced less pain during heel puncture than the other groups (p < 0.05).
A46⁵⁹	Spain/ 2021/ 106 NBs/ III.2	Assess neonatal pain during metabolic screening. Experimental study	Oral serum glucose and breastfeeding.	The pain produced was significantly greater in the no intervention group compared to the saline or breastfeeding groups (p < 0.001). However, no statistically significant differences were found between the two analgesic procedures (p = 0.851).
A47⁶⁰	China/ 2021/ 116 NBs/ II	Assess the effect of maternal voice on pain caused by venipuncture (including peripheral venipuncture and femoral venipuncture) in infants admitted to the NICU. Randomized controlled experimental study	Auditory stimulus with recorded maternal voice.	The study showed that pain scores, behavioral indicator scores and physiological indicator scores in the maternal voice group were significantly lower compared to those in the routine care group.
A48⁶¹	Brazil/ 2021/ 52 NBs/ II	Assess the effect of music, applied for ten and 15 minutes, combined with swaddling, on behavioral (facial action) and physiological (HR) responses to pain in full-term NBs before and during venipuncture for blood collection. Randomized, triple-blind clinical trial	Swaddling and music therapy.	The experimental group in which music was applied (15 minutes) plus swaddling showed a high absence of pain (p < 0.05) and a low mean HR (p < 0.0001) at baseline and during the procedure.
A49⁶²	Turkey/ 2021/ 128 NBs/ II	Determine the effect on the level of pain and comfort of foot massages given by mothers to NBs before heel. Double-blind randomized controlled experimental study	Oil massage by mothers.	It was determined that mothers’ foot massage reduced the NBs’ pain level, increasing their comfort levels and decreasing their distress levels.
A50⁶³	China/ 2021/ 96 NBs/ II	Explore the effect of breast milk sucking (BMS) on pain relief from neonatal heel blood sampling. Randomized clinical trial	BMS.	Crying time and bleeding time of NBs in the BMS group were significantly shorter than those in the CG (p < 0.05). The total pain scale score of the BMS group was lower than that of the CG (p < 0.05).
A51⁶⁴	Austria/ 2021/ 96 NBs/III.1	Investigate whether laser acupuncture is not inferior to oral sweet solutions in preventing pain. Clinical trial	Laser acupuncture with 10 mW in LI4 bilaterally and administration of 30% oral glucose solution.	Median pain scores were comparable in the acupuncture group and the glucose group (12 (10-14) versus 12 (9-14), p = 0.981). HR was significantly lower after the intervention (p = 0.048) and after heel puncture (p = 0.015) in the acupuncture group versus the glucose group. There was no difference in crying time between groups (p = 0.890).
A52 ⁶⁵	Turkey/2021/ 64 mothers with NBs/ II	Assess the effectiveness of NPMs in neonatal pain management; explore anxiety-related outcomes; and examine the implementation of pain management training during the heel prick sampling procedure. Randomized clinical trial	Expressed BM, swaddling, SSC, hold and smooth sounds.	It demonstrated that when nurses recommended NPM for neonatal pain management, maternal participation in pain management increased significantly.
A53⁶⁶	Poland/ 2022/ 90 NBs/ II	Assess the severity of pain felt by a NB during a screening heel puncture using the NIPS, in addition to measuring HR and comparing the effectiveness of NPM for pain management. Randomized clinical trial	Breastfeeding, 20% oral glucose and NNS.	No statistically significant differences were found between the degree of pain intensity and the intervention used to minimize pain (p = 0.24).
A54⁶⁷	Turkey/ 2022/ 90 NBs II	Compare the effects of breastfeeding, BM odor and the sounds of mothers’ heartbeat on pain perceived during heel puncture in full-term NBs. Randomized experimental study	Breastfeeding, olfactory stimulation with BM odor, auditory stimulation with the sounds of mothers’ heartbeat.	During the procedure, NBs in the BM odor group presented high levels of pain and stress; NBs in mothers’ heart sound group presented mild pain and stress; and NBs in the breastfeeding group did not present pain and stress.
A55⁶⁸	India/ 2022/ 100 NBs/ II	Assess the effectiveness of SSC versus swaddling in pain response to intramuscular injection of vitamin K at 30 minutes after birth in NBs. Randomized and controlled clinical trial	SSC and swaddling.	The pain scale score was comparable between SSC and swaddling before [1.78 (0.58) versus 1.96 (0.83), p = 0.21] and immediately after injection [4.82 (0.72) versus 5.08 (0.75), p = 0.08].
A56⁶⁹	Turkey/ 2022/ 100 NBs/ II	Determine the effect of using a crochet octopus to reduce acute pain and maintain optimal physiological measures that develop during procedural pain in infants. Parallel design randomized controlled study	Crochet octopus.	Infant saturation, touching the crochet octopus during and after the second minute of the procedure, was greater, and crying duration was shorter throughout the procedure, and the pain they felt due to the process was less than in the CG.
A57⁷⁰	Iran/2022/ 60 NBs/ III.1	Investigate the effect of the concomitant use of swaddling and sucrose taste on pain intensity during venous blood collection in infants. Clinical trial	Concomitant application of swaddling and sucrose taste.	The results showed a significant difference between the mean pain intensity in infants in the sucrose-swaddling group (4.53 ± 1.30) and the sucrose (7.73 ± 2.73), swaddling (9.86 ± 33, 33) and control (12.13 ± 2.06) during blood sampling (P <0.001).
A58⁷¹	Turkey/ 2022/ 56 NBs/ II	Assess the effect of applying vibration to control pain during heel puncture procedures in NBs. Randomized and controlled clinical trial	Vibration.	Pain scores were significantly lower at 15 to 20 seconds and five minutes after heel puncture procedures in the vibration group than in the CG (p < 0.05).
A59⁷²	Turkey/ 2022/120 NBs/ II	Comparatively investigate the effectiveness of BM taste and/or smell in reducing pain responses in NBs undergoing a blood collection procedure. Prospective randomized controlled study	Administration of olfactory stimulus with BM odor and administration of gustatory stimulus of BM.	During and after the procedure, there were significant differences in pain levels, oxygen saturation and HR between groups (p = 0.000). The lowest pain score during the procedure was found in NBs to whom BM taste and smell were administered together.
A60 ⁷³	Turkey/ 2023/ 96 NBs/ II	Examine the effect of regional massage performed before blood sampling on pain and vital signs in full-term NBs. Randomized clinical trial	Massage in the blood collection region.	NBs in the experimental group had shorter crying times, lower levels of pain and HR and higher oxygen saturation than those in the CG.
A61 ⁷⁴	Turkey/ 2024/ 50 NBs/ III.2	Determine the effect of breastfeeding on the behavioral pain and comfort scores of NBs during heel blood sampling. Pre-test/post-test experimental-control study	Breastfeeding during heel blood sampling.	Regional massage intervention reduced pain in full-term NBs. Breastfeeding is an important nursing intervention to reduce procedural pain in NBs. The breastfeeding method reduces pain and discomfort and increases NBs’ comfort during the heel blood collection process.

1 Article code/ 2 Participants/3 Level of Evidence.

DISCUSSION

Oral sweet solution administration – sucrose, glucose and dextrose

The effect of different concentrations of sucrose on reducing pain in painful procedures, such as heel puncture and vaccination, was verified, with significant impacts on the duration of crying and HR after administration of the solution in healthy NBs, which demonstrates that the use of this solution can be safe and useful for minor procedures in these patients.¹⁶ Furthermore, increasing concentrations of sweet solution provides a significant tendency to reduce pain and crying time, with 30% glucose presenting lower pain scores when compared to 20% and 10%,²⁴and sucrose 50% compared to variations of 12.5% and 25% and 50%.¹⁴ The same efficacy results were found for 10% dextrose⁴⁴ and 24% sucrose administered orally.⁵¹

When used in combination with other NPM, it appears that sweet solutions can obtain better results in reducing pain in NBs. A study that used sucrose combined with radiant heat compared to the taste of sucrose alone concluded that sucrose combined with heat group cried and grimaced for 50% less time after vaccination compared to the sucrose alone group, reflecting a greater ability to physiologically regulate the response to painful procedures.³⁷

BM was also compared to 20% sucrose to ascertain its ability to mitigate pain in NBs, identifying that the mean pain score for the group that received BM was significantly higher than that of sucrose.⁴⁷ In another study, SSS, SSBM and isolated oral sucrose (24%) were performed in infants undergoing venipuncture. It was demonstrated that SSBM and SSS were more effective than oral sucrose alone (24%) (p = 0.001), but no difference was observed between SSBM and SSS (p = 0.669).⁵³ In fact, the analgesic effect of BM seems to be limited when offered expressed, without the act of breastfeeding, since a study that assessed the provision of 2 mL of foremilk, hindmilk or sterile water did not find statistically significant differences between the three groups in terms of crying time in NBs.¹⁷

The sucrose solution’s analgesic effect demonstrated is related to the rapid action that this glucose and fructose disaccharide has, although the literature does not present a consensus regarding the durability of its analgesic action.^14,21 Furthermore, it is necessary to consider that, although sweet solutions, such as sucrose, are widely administered to hospitalized NBs for single painful procedures, the total volume during the entire stay in health services and associated adverse events are poorly known.⁷⁵ Finally, it should be noted that there are contraindications for its use, such as high risk of necrotizing enterocolitis, food intolerance, esophageal atresia or tracheal-esophageal fistula or persistent pulmonary hypertension in the active phase.⁷⁶

Breastfeeding

Breastfeeding as NPM for pain management in NBs is well documented in the scientific literature, especially with regard to minor painful procedures. This practice is capable of reducing crying duration, being significantly shorter when compared to routine care.⁵⁰

A significant number of studies also used breastfeeding combined with other methods to compare their effect on reducing pain in NBs. In all studies, this NPM showed lower pain scores and duration of crying, confirming that breastfeeding has superior pain-reducing effects in NBs undergoing venipuncture,¹⁸ heel punctures²¹ and vaccination.⁵⁰ However, although studies identify a relatively greater reduction in pain scores during breastfeeding compared to sweet solution administration (glucose or sucrose), no statistically significant differences were observed between the proposed interventions.^59,18

In 2015, the World Health Organization released recommendations for national immunization programs on interventions to mitigate pain and fear at the time of vaccination; for children, the presence of caregivers and breastfeeding practice were recommended.⁷⁷ Subsequently, in October 2021, the Brazilian Ministry of Health (MoH) issued a technical note (Technical Note 39/2021) that endorses breastfeeding as a non-pharmacological measure to reduce pain and discomfort in children during injectable vaccine application. Therefore, it is recommended that healthcare professionals encourage nursing mothers to breastfeed children immediately before and during injectable vaccine administration,⁷⁸ a conduct that can also be encouraged during other painful procedures.

Despite the endorsement of government organizations and researchers, nursing professionals’ and parents’ belief in the possibility of risks occurring, such as choking, coughing, vomiting, among others, may discourage breastfeeding while NPM to reduce neonatal pain during painful procedures.⁷⁹ However, a systematic review of the Cochrane database, with the aim of determining the effect of breastfeeding on procedural pain in children up to one year of age, identified that none of the included studies reported complications related to breastfeeding during invasive procedures, thus suggesting that there is no risk of adverse effects such as those mentioned.⁸⁰

Non-nutritive sucking

NNS was considered a safe and effective method of pain relief during NB procedures. A pacifier was used, in most studies, as an instrument to carry out the intervention. In all studies assessed, the mean pain, discomfort and crying scores were significantly lower in the NNS group than in the no pain management group.^20,54

This NPM was also assessed comparatively to other interventions to mitigate pain in NBs, proving to be effective when compared to groups of children who underwent Yakson,¹⁹ and administration of glucose diluted with 25% sterile water.²³ In only one study, the use of sucrose was more effective in reducing pain and crying time in NBs compared to NNS (pacifier).²⁵

The combined application of NNS with other NPMs also showed the potential to increase pain reduction, as in the association of NNS and sucrose, compared to NNS and placebo, with significant differences being observed in both the pain scale score and crying time.^20,32 When associated with breastfeeding and administration of 20% glucose orally, no statistically significant differences were found between the degree of pain intensity and the intervention used to minimize pain. Despite that, the results indicate that each of the non-pharmacological interventions (breastfeeding, oral glucose dosage and NNS) applied during painful procedures resulted in effective pain management in the majority of NBs included in the study.⁶⁶

Kangaroo Mother Care (kangaroo position) and skin-to-skin contact

KMC, also known as SSC, is considered effective in relieving pain in NBs that occurs during various procedures performed in routine healthcare.⁸¹ It has been found that during painful procedures, SSC between mother and child can alleviate pain,^33,46 reduce changes in HR, improve oxygen saturation in neonatal heel blood, and improve emotional communication between mother and child.³³ It is also evident that NBs who receive SSC cry less compared to CGs, reaching a calm behavioral state sooner and tending to a faster decrease in HR.²⁷

When applying SSC in hepatitis B vaccine intramuscular injection compared to 25% dextrose administration, it was demonstrated that SSC reduced pain and injection duration, but that the combination of the two analgesic measures was more effective than either measure separately for full-term NBs.²²

KMC combines skin-to-skin body contact and hearing a familiar voice, which contributes to infants’ self-regulation. It is useful not only in reducing neonatal mortality, but also in reducing procedural pain, which occurs during routine procedures or during diagnostic examinations, regardless of whether the mother or father has performed the kangaroo position.⁸¹

Swaddling

NB swaddling, a technique also known as wrapping, is a NPM commonly used to reduce pain perception in infants for invasive procedures such as heel puncture, venipuncture and vaccination,⁶⁸ and consists of swaddling or wrapping a child in a cloth.²² The mean pain scores of NBs swaddled during and after the procedure are lower than the scores of non-swaddled NBs, as is crying duration.⁴³

However, when used in conjunction with other NPMs, it does not appear to have a superior effect. A study with the objective of comparing swaddling, KMC and breastfeeding in vaccination in NBs concluded that breastfeeding has a higher success rate in painless vaccination and shorter duration of crying compared to other methods.³⁹ Following the same direction, SSC compared to swaddling has a lower pain score than at baseline, whereas it is significantly higher in swaddling, demonstrating that immediate SSC is more effective than swaddling as a pain management intervention.⁶⁸

On the other hand, combined application with other NPMs demonstrates evidence of a significant synergistic analgesic effect, such as when applied in conjunction with NNS and oral sucrose in both superficial and deep puncture procedures. Although capable of reducing pain, NNS has been shown to exhibit lower pain scores than swaddling.³⁵ There is also a significant difference between the mean pain intensity in NBs who receive sucrose-swaddling than sucrose or swaddling alone, and it is recommended that the combined swaddling-sucrose method be used in NBs as the best analgesic.⁷⁰

Other NPMs, although studied in smaller numbers, are effective in managing NB pain, namely: olfactory stimulation using vanillin compared to a familiar smell, which demonstrated better effectiveness in reducing crying and oxygen consumption during arterial puncture;²⁸ olfactory stimulus with the smell of lavender associated with 30% edible glucose, presenting itself as an easy and applicable nursing care to reduce blood collection pain in full-term NBs;⁵² auditory stimulus with mothers’ voice, whose findings showed the effect of mothers’ voice in reducing pain in infants;³¹ vibration, whose studies have demonstrated significantly lower pain scores during painful procedures than those in the no vibration group;^40,71 massage, which reduced crying time, pain levels and HR, increasing oxygen saturation in NBs who received the intervention.⁷³

On the other hand, methods with no or little effectiveness were also verified, such as olfactory stimulation with vanilla aroma oil, which had no impact on pain levels,²⁹ BM odor, with NBs presenting high levels of pain and stress,⁶⁷ and music therapy alone, which does not seem to increase the pain relief effect of breastfed NBs.³⁸

CONCLUSION

Studies show that the use of NPM is a safe, low-cost and effective option for reducing pain and stress in NBs undergoing invasive procedures. Sweet solution administration and breastfeeding are the two most relevant methods, with the second standing out among all the methods assessed. Furthermore, the use of these combined interventions can provide even more positive results in reducing pain in NBs, presenting a synergistic effect when applied together.

The study is limited by the lack of research that assesses specificities in the application of methods, such as the ideal time for completion and the most favorable procedures for use. As an implication for Brazilian public health, it is envisioned that the results of this research can be synthesized and incorporated into the basic and continuing training of healthcare professionals, both in terms of the hospital context and in Primary Health Care, with the aim of making pain management in NBs more humanized and guided by scientific evidence.

CONTRIBUTIONS

Fernandes LSL, Brito MA and Rocha RC contributed to data analysis and interpretation and writing. Lopes TP contributed to data analysis and interpretation. Bezerra MAR contributed to conception, study planning, writing and critical review. Carneiro CT contributed to data analysis and interpretation, writing and critical review. Carvalho ILN and Moura MAP contributed to writing.

CONFLICTS OF INTERESTS

There were no conflicts of interest.

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Maria Augusta Rocha Bezerra

Email: mariaaugusta@ufpi.edu.br

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Non-pharmacological methods for pain relief in newborns: an integrative literature review

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