Evidence map›Paper›PMID 40148770›Full record

SynthesisBMC pediatrics2025

Assessment of cortisol as a neonatal pain biomarker in the application of non-pharmacological analgesia therapies: systematic review and meta-analysis.

Inmaculada García-Valdivieso, Jorge Sánchez-Infante, Pablo Pando Cerra, Benito Yáñez-Araque, Sonsoles Hernández-Iglesias, Fernando Peña Cambón, Celia Álvarez-Bueno, Abel Checa Peñalver, Juan Manuel Pérez-Pozuelo, Sagrario Gómez-Cantarino

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in BMC pediatrics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Sucrose analgesia for venepuncture in neonates.The Cochrane database of systematic reviews · 2026
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Inmaculada García-ValdiviesoFaculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, 45071, Spain.
Jorge Sánchez-InfanteFaculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, 45071, Spain.
Pablo Pando CerraDCIF University of Oviedo, Asturias, 33203, Spain. pandopablo@uniovi.es.
Benito Yáñez-AraqueDepartment of Business Administration, School of Industrial and Aerospace Engineering, University of Castilla-La Mancha, Toledo, 45071, Spain.
Sonsoles Hernández-IglesiasFaculty of Health Sciences, Francisco de Vitoria University, Madrid, 28223, Spain.
Fernando Peña CambónDCIF University of Oviedo, Asturias, 33203, Spain.
Celia Álvarez-BuenoHealth and Social Research Center, University of Castilla-La Mancha, Cuenca, 16071, Spain.
Abel Checa PeñalverFaculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, 45071, Spain.
Juan Manuel Pérez-PozueloFaculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, 45071, Spain.
Sagrario Gómez-CantarinoFaculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, 45071, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn the history of Neonatology, decades ago pain has been little studied because it was believed that newborns didn't have the capacity to experience pain. Nowadays, there is enough evidence for the existence of neonatal pain but its adequate treatment is an aspect that is continuously evolving. The objective of this study was to evaluate the effectiveness of non-pharmacological analgesia therapies used to alleviate pain in newborns by analysing neonatal cortisol levels as biological markers of pain.

methodsA systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Cochrane Collaboration Handbook. Searches were performed in databases such as PubMed, Web of Science, Scopus, CINAHL, Cochrane Library and Science Direct until the end of May 2024. The search identified 1075 articles, of which 10 studies met the inclusion criteria and had the necessary data to develop the meta-analysis. Furthermore, in each meta-analysis, subgroups were performed: non-pharmacological analgesia vs. placebo, and pre-post intervention by gestational age.

resultsThe meta-analysis found that breastfeeding exhibited a moderate effect size (SMD = -0.63; 95% CI = -1.07 to -0.19), sucrose showed a small effect (SMD = -0.15; 95% CI = -0.55 to 0.26), and skin to skin contact exhibited a large effect (SMD = -1.34; 95% CI = -2.21 to -0.46). Patients under 28 weeks have less post-intervention pain and showed a large effect (SMD = 1.44; 95% CI = 0.47 to 2.40), between 28 and 32 weeks they have more post-intervention pain and presented a small effect (SMD = -0.43; 95% CI = -0.86 to -0.0), and over 32 weeks they have an increased post-intervention pain and exhibited a large effect (SMD = -1.08; 95% CI = -1.65 to -0.51).

conclusionsNon-pharmacological therapies showed efficacy in pain reduction based on neonatal cortisol levels. Skin to skin contact is the most effective method to reduce pain from invasive procedures, such as heel pricks in preterm infants under 28 weeks. Breastfeeding also demonstrated to be an effective and safe alternative to use for pain relief and to reduce cortisol levels. However, the cortisol results indicate that sucrose was not effective in reducing neonatal pain.

trial registrationPROSPERO: CRD42023463831.

Indexed as

AnalgesiaHydrocortisonePainPain ManagementBiomarkersBreast FeedingHumansInfant, NewbornPain MeasurementBiomarkersHydrocortisoneAnalgesiaBreastfeedingCortisolHeel PrickNeonatal painNewbornNursing careSkin to skin contactSucrose

Identifiers

PMID40148770
PMCPMC11951685

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.