To Örebro University

Background: Engaging parents in parent-delivered pain relief in routine postnatal care is aligned with evidence-informed infant pain care and should be encouraged. This is part two of the mixed-methods SWEpap research project investigating combined parent-delivered pain management. Skin-to-skin contact (SSC) and breastfeeding are among the most studied parental pain-relieving interventions and are often combined for better effects. Live parental lullaby singing has not previously been investigated in combination with SSC and breastfeeding during painful procedures. This study investigated the efficacy of combined parent-delivered pain management versus standard care with oral glucose in healthy newborn infants during routine venipuncture.

Methods: This was a multicenter randomized controlled trial with three parallel groups. Parent–infant dyads (n= 225) were recruited from three healthcare regions in Sweden and randomized to one of the following three groups during routine venipuncture: 1) standard care with glucose; 2) SSC with parent; and 3) combination of SSC, breastfeeding (if applicable), and parents’ live singing. The primary outcome was pain expression assessed using Premature Infant Pain Profile—Revised (PIPP-R); the secondary outcomes were galvanic skin response (GSR) and parents’ evaluations of pain, stress, and meaningfulness using a visual analogue scale (VAS).

Results: The median PIPP-R was 5 (IQR 3–6) for group 1, 7 (5–9) for group 2, and 7 (5–10) for group 3 (p< 0.001). There were no significant differences in GSR. Parents’ VAS-assessment of infant pain ranged from a median of 9.5 to 17 mm, significantly higher in groups 2 and 3 (p= 0.017). The parents rated their own stress 4.5 - 6.5 (n.s.) and meaningfulness 93 - 96 (n.s.).

Conclusion: Pain scores remained within the mild to moderate range across all groups, with the infants receiving oral glucose having significantly lower pain scores. This was the first study combining SSC, breastfeeding, and parents’ live lullaby singing, and more research is needed to optimize parent-delivered pain management. Parent-delivered pain management combining SSC, breastfeeding, and parents’ live lullaby singing is a feasible and safe intervention with potential pain alleviating properties offering the parents a strong sense of meaningfulness and stress relief.

Objectives: Urgent action is needed to protect infants’ rights to parental presence during painful procedures in neonatal care. Although the infant’s access to the comforting presence of parents has improved, significant attitudes and beliefs among health care providers continue to limit parents' inclusion as partners in neonatal care management. Facilitating parent-led neonatal pain management is the central aim of the multinational research and dissemination initiative POP (Parent-led pain management to Optimize neonatal Pain care). The POP Study is co-designed by parents, researchers and clinicians in a common effort to improve neonatal pain management. 

Material and Methods: POP advocates for a call to action to improve infant pain management by including parents at all stages of care, including shared decision-making regarding assessment, plan, provision, and evaluation. By shifting the role of researchers from experts to collaborators, POP promotes shared authority in defining priorities and advancing neonatal pain care. 

Results: Parent partners within POP bring firsthand experience with the evolution of evidence-based neonatal pain management guidelines. Moreover, as both parents and advocates, they have lived experience that these guidelines frequently fail to translate into consistent bedside clinical practice. As one parent partner says: “We are protective regulators for our children, and our involvement in pain mitigation is both emotionally essential and scientifically supported. Guidelines matter, but only when they are lived in practice”.

Conclusions: A substantial and growing body of evidence supports that parent-led pain management—implemented in collaboration with healthcare providers and supported by shared decision-making—significantly reduces procedural pain associated with repeated common painful procedures. The POP research group calls for global implementation to ensure that every infant, regardless of birthplace, has access to parent-led pain management during common painful procedures.

Purpose This study aims to analyze global prescribing patterns for analgosedation in neonates during four critical care scenarios. The research explores existing patterns, their association with geographic and sociodemographic index (SDI), and adherence to evidence-based practices.

Methods Data from a 2024 global survey of 924 responses to 28 questions were analyzed, focusing on four items for their high variability: premedication in intubation (Q17), sedation in preterm (Q19) and full-term newborns (Q23), and perinatal asphyxia (Q26). Latent class analysis (LCA) classified neonatal intensive care unit (NICU) prescriptions into patterns, assigning participants to the most likely class. Demographic variables, including geographic region and SDI, were compared using chi-square tests to assess associations.

Results Three distinct prescribing patterns emerged for each scenario. In premedication during intubation, Europe and North America predominantly used Class 1, adhering to guidelines with fentanyl, atropine, and muscle relaxants. In contrast, Class 2, standard in Asia and Latin America-Caribbean, primarily utilized fentanyl and midazolam, with rare use of atropine and muscle relaxants. For analgosedation in newborns, higher-SDI NICUs favored fentanyl, while lower-SDI NICUs preferred midazolam or morphine combinations. In perinatal asphyxia cases, fentanyl was the leading choice in Class 3, especially in Europe. Dexmedetomidine use was limited, primarily appearing in Class 1 NICUs. 

Conclusion The study highlights substantial regional variability in neonatal analgosedation, influenced by SDI and geography. Despite established guidelines, gaps in evidence-based implementation persist. These findings underscore the need for global standardization of neonatal care protocols and further research on the long-term safety of midazolam and dexmedetomidine. 

Background/ObjectiveHospitalized neonates are subjected to a high number of painful procedures every day. Cumulative poorly treated pain can have negative consequences on short and long-term outcomes, negative effects that are further amplified by infant-maternal separation. Research has shown that parents want to be part of their hospitalized infants pain management and that it is safe and effective. Yet, the implementation of parent-led pain management in neonatal care is sub-optimal. The overall aim of the project is to expand parent-led neonatal pain management, resulting in less infant pain and potentially better neonatal health outcomes, along with improved parent mental health and well-being.

Method The project is carried out by an international research group with researchers and parent representatives from Canada, Finland, Italy and Sweden, and will follow the British Research Council’s framework for complex interventions. It is organized into four work packages (WPs): Theory and concept (WP1), Identifying the problem (WP2), Developing an instrument and algorithm for self-audit (WP3), and Intervention and implementation (WP4). Principles for patient-public involvement will also be followed, with parent representatives involved in planning and designing the project and when applicable in data collection and publication of results.

ResultAn international team consisting of clinicians, researchers and parent partners across four countries have commenced initial work from WP1: writing a position paper, performing a literature review, and conducting an analysis of the concept of parent-led pain management.

ConclusionThe POP-project builds on the contribution of parents, researchers and clinicians and has the potential to improve implementation of parent-led pain management for neonates world-wide.

BACKGROUND: Premature neonates often require mechanical ventilation during intensive care. However, there is a lack of clinical consensus on the provision, type, and dosage of analgosedatives. The purpose of this scoping review is to assess the risks and benefits of providing analgesic and sedative drugs to ventilated premature infants.

METHODS: We sourced primary empirical research reporting outcomes related to the use of pharmacological analgesics and sedatives in ventilated premature infants. We included articles published in any language in peer-reviewed journals before February 2024 from MEDLINE, Embase, Web of Science, Cochrane Library, and Google Scholar databases. We present the overall study characteristics, and the reported risks and benefits of analgosedatives within drug sub-groups.

RESULTS: 80 studies were included in the scoping review. Morphine was the most studied drug (39 studies), followed by fentanyl (19 studies). Midazolam (8 studies) and dexmedetomidine (3 studies) were the most frequently studied sedatives. Analgesic efficacy was more consistently reported for fentanyl than morphine. The sedative effect of opioids was rarely assessed. Respiratory, cardiovascular, gastrointestinal, neurological and neurodevelopmental risks were unclear for all opioids. Alternative synthetic opioids and midazolam appear to be associated with significant risks in the absence of clear benefits. Dexmedetomidine shows encouraging but limited results and merits further investigation as an opioid-sparing adjunct.

CONCLUSION: At present, fentanyl appears to have the best efficacy and safety profile for analgosedation in this patient population. This scoping review will support clinicians in their analgosedative management of ventilated premature infants and identifies research gaps and priorities.

IMPACT: This systematic scoping review provides a comprehensive summary of the evidence of the risks and benefits of analgesics and sedatives in ventilated premature infants. Although morphine is the most extensively studied and used drug, its analgesic effect has been less consistently reported than that of fentanyl. Sedation has rarely been assessed and dexmedetomidine seems a promising sedative adjunct as midazolam use is not supported by evidence.

BACKGROUND: Six to nine per cent of all newborn infants require admission to a neonatal intensive care unit (NICU) due to either illness or prematurity. During their stay, these infants are often subjected to many painful procedures that can cause negative long-term consequences. To reduce the negative effects of pain exposure and ensure optimal and safe pain treatment, accurate assessment of pain is necessary. To achieve this, clinicians are dependent on the use of reliable, objective, and standardised clinical rating scales of pain, henceforth referred to as 'rating scales'. Numerous rating scales have been published; however, discrepancies in validity limit their overall applicability in clinical practice and research. Such limitations may lead to an over- or underestimation of pain, resulting in unnecessary sedation or inadequately treated pain, potentially jeopardising infant safety through treatment side effects, including withdrawal symptoms or prolonged discomfort. To date, the majority of rating scales have been developed to assess procedural pain, whilst fewer scales for prolonged pain are available. Premature infants further complicate matters, as they often have a reduced ability to display robust pain behaviour due to their immaturity. Research has also shown that the use of rating scales in clinical practice is suboptimal, due to both inadequate and infrequent implementation alongside inappropriate choice of scale for the specific pain, population, or setting under evaluation. Despite numerous studies investigating the burden of pain in newborn infants, little work has been done to summarise the current evidence on the appropriateness of rating scales for specific types of pain or infant conditions. This has likely been limited by the subjectivity of pain assessment and further complication of assessing such a non-verbal and immature patient population. The immense burden of neonatal pain worldwide has also led to the development of numerous rating scales in various languages, further hindering evidence summation.

OBJECTIVES: To systematically review the literature to compile and describe the development, content, and measurement properties of clinical rating scales for the assessment of pain in newborn infants.

SEARCH METHODS: An Information Specialist systematically searched CENTRAL, PubMed, Embase, and CINAHL. The latest update search is current to July 2023.

SELECTION CRITERIA: We included all study designs that involved the development or testing of a rating scale for assessing pain in newborn infants. We included preterm (born before week 37) and term (born at week 37 or beyond) infants undergoing pain assessment for any medical indication. We also included studies that included healthcare professionals.

DATA COLLECTION AND ANALYSIS: We evaluated clinical rating scales assessing pain in newborn infants using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology evaluating content validity, structural validity, internal consistency, reliability, measurement error, hypothesis testing, and cross-cultural validation. We used a modified GRADE approach to assess risk of bias, inconsistency, imprecision, and indirectness.

MAIN RESULTS: We included 79 studies involving a total of 7197 infants, 326 nurses, and 12 physicians. Twenty-seven clinical rating scales were used in 26 countries, with 14 studies evaluating preterm infants, 11 on term infants, 46 on both preterm and term infants, four solely on medical staff, and four on preterm and/or term infants plus medical staff. Following the COSMIN checklist, we found all rating scales to be of very low-certainty evidence, raising concerns regarding their validity, reliability, and applicability in this vulnerable population across diverse clinical settings.

AUTHORS' CONCLUSIONS: Clinical staff should be vigilant when applying the currently available neonatal rating scales. Further development of rating scale content and testing for structural validity are necessary and should be prioritised. Together, they determine the content and structure of rating scales, underpin further testing, including reliability, and their prioritisation will make the greatest contribution to the evidence base for rating scales to assess neonatal pain. Collaborative efforts between clinicians and methodology experts will prevent methodological pitfalls and contribute to improving the validity and reliability of pain-rating scales in neonatology.

Background Parents are a valuable but underutilizedresource in neonatal pain management. Involving parentshave shown to be efficient for pain relieving and combiningseveral parent-delivered methods could increase the effect.

Aim The aim of this study was to investigate the pain-relieving effects of parent-delivered pain managementcombining skin to skin contact (SSC), breastfeeding, andlive parental lullaby singing compared with SSC alone andwith standard care using oral glucose in healthy newborninfants.

Material and method Multicenter randomizedcontrolled trial with three parallel groups during routineblood sampling in postnatal care. Parent-infant dyads(n=225) were recruited from three health care regions inSweden and randomized to one of the three groups; 1 –standard care with oral glucose, 2- SSC 3 – a combinationof SSC, breastfeeding (if applicable) and live parentallullaby singing. Primary outcome was pain expressionassessed with Premature infant pain profile –Revised(PIPP-R), secondary outcomes were skin conductance andparents’ evaluation of pain, stress and meaningfulness.

Results Median PIPP-R was 5 (IQR 3–6) for group 1, 7(5–9) for group 2, and 7 (5–10) for group 3 (p < 0.001).There were no significant differences in skin conductance.Parents’ VAS-assessment (Figure 1) of infant pain rangedfrom a median of 9.5 to 17 mm, significantly higher ingroups 2 and 3 (p = 0.017). The parents rated their ownstress as low 4.5 - 6.5 mm and very high formeaningfulness 93 - 96 mm.

Conclusion This was the first large RCT to evaluate combined parent-delivered painmanagement including parents’ live singing. Pain scores remained within the mild to moderate range across all groups, with the infants receiving oral glucose having significantly lower pain scores. The results indicated that involving parents leads to low stress and high sense of meaningfulness. Combined parent-delivered pain management is feasible and safe.

Study protocol