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Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions. Methods: A web-based survey was distributed to neonatal units worldwide. Results: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always. Conclusions: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of pain management of 1 ml of 24% sucrose given orally compared to routine care given one minute before vaccination for reduction of pain. Methods: This double-blind randomized controlled trial included term neonates visiting Pediatric OPD for immunization. Neonates were randomly assigned into two groups (Group A- Sucrose, Group B- Swaddling). Commercially available sucrose solution (StayHappi solution 24%) was given in a dose of 1 ml to the neonates. Video recording of the neonate's facial expression was done during the procedure. Duration of cry, latency of onset of cry as well Modified Neonatal Facial Coding Score (MFCS) were the outcome variables. Results: The mean (SD) of birth weight and gestational age was 2729 (321.6) g and 38.24 (0.84) d, respectively. Analysis showed significant difference in total MFCS across the groups (P <0.001). Total MFCS was significantly lower in sucrose group [4.88 (1.07) vs. 7.17 (0.95)]. The duration of cry (in seconds) was also found to be significantly lower in sucrose group. Conclusions: Administration of 1 ml 24% sucrose one minute prior to immunization is efficacious in pain management during injectable immunization. [ABSTRACT FROM AUTHOR]

We analyzed plasma melatonin levels in different groups of preterm newborns without hypoxia and their relationship with several perinatal variables like gestational age or neonatal pain. Prospective cohort study of preterm newborns (PTNB) without perinatal hypoxia, Apgar > 6 at 5 min, and oxygen needs on the third day of life. We compared melatonin levels at day 3 of life in different groups of non-hypoxic preterm infants (Student's t-tests, Mann-Whitney U, and chi2) and analyzed the relationship of melatonin with GA, birth weight, neonatal pain (Premature Infant Pain Profile (PIPP) scale), caffeine treatment, parenteral nutrition, or the development of free radical diseases (correlation study, linear regression) and factors associated with moderate/intense pain and free radical diseases (logistic regression analysis). Sixty-one preterm infants with gestational age (GA) of 30.7 ± 2.0 weeks with no oxygen requirements at day 3 of life were studied with plasma melatonin levels of 33.8 ± 12.01 pg/ml. Preterm infants weighing < 1250 g at birth had lower plasma melatonin levels (p = 0.05). Preterm infants with moderate or severe pain (PPIPP > 5) have lower melatonin levels (p = 0.01), and being preterm with PIPP > 5 is associated with lower plasma melatonin levels (p = 0.03). Being very preterm (GA < 32 GS), having low weight for gestational age (LWGA), receiving caffeine treatment, or requiring parenteral nutrition did not modify melatonin levels in non-hypoxic preterm infants (p = NS). Melatonin on day 3 of life in non-hypoxic preterm infants is not associated with later development of free radical diseases (BPD, sepsis, ROP, HIV, NEC). Conclusion: We observed that preterm infants with moderate to severe pain have lower melatonin levels. These findings are relevant because they reinforce the findings of other authors that melatonin supplementation decreases pain and oxidative stress in painful procedures in premature infants. Further studies are needed to evaluate whether melatonin could be used as an analgesic in painful procedures in preterm infants. Trial registration: Trial registration was not required since this was an observational study. What Is Known: • Melatonin is a potent antioxidant and free radical scavenger in newborns under stress conditions: hypoxia, acidosis, hypotension, painful procedures, or parenteral nutrition. • Pain stimulates the production of melatonin. • Various studies conclude that melatonin administration decreases pain during the neonatal period. What Is New: • Non-hypoxic preterm infants with moderate to severe pain (PIPP>5) have lower levels of melatonin. • Administration of caffeine and treatment with parenteral nutrition do not modify melatonin levels in non-hypoxic preterm infants. [ABSTRACT FROM AUTHOR]

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety. Important obstacles contributing to inadequate studies in preterm/sick infants include difficulties in obtaining parental consent, physicians' unwillingness to recruit preterm infants, the off-label use of many medications in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials (antifungals), analgesics (sedatives), and antiseizure medications in neonates, focusing on current evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage, and evidence-based guidelines for their optimal use in neonates. We also address the effects of early antibiotic use on the intestinal microbiome and its association with long-term immune-related diseases, obesity, and neurodevelopment (ND). Recommendations for empirical treatment and the emergence of pathogen resistance to antimicrobials and antifungals are also presented. Finally, future perspectives on the prevention, modification, or reversal of antibiotic resistance are discussed. [ABSTRACT FROM AUTHOR]

Background: Early-life pain is associated with adverse neurodevelopmental consequences; and current pain assessment practices are discontinuous, inconsistent, and highly dependent on nurses' availability. Furthermore, facial expressions in commonly used pain assessment tools are not associated with brain-based evidence of pain. Purpose: To develop and validate a machine learning (ML) model to classify pain. Methods: In this retrospective validation study, using a human-centered design for Embedded Machine Learning Solutions approach and the Neonatal Facial Coding System (NFCS), 6 experienced neonatal intensive care unit (NICU) nurses labeled data from randomly assigned iCOPEvid (infant Classification Of Pain Expression video) sequences of 49 neonates undergoing heel lance. NFCS is the only observational pain assessment tool associated with brain-based evidence of pain. A standard 70% training and 30% testing split of the data was used to train and test several ML models. NICU nurses' interrater reliability was evaluated, and NICU nurses' area under the receiver operating characteristic curve (AUC) was compared with the ML models' AUC. Results: Nurses weighted mean interrater reliability was 68% (63%-79%) for NFCS tasks, 77.7% (74%-83%) for pain intensity, and 48.6% (15%-59%) for frame and 78.4% (64%-100%) for video pain classification, with AUC of 0.68. The best performing ML model had 97.7% precision, 98% accuracy, 98.5% recall, and AUC of 0.98. Implications for Practice and Research: The pain classification ML model AUC far exceeded that of NICU nurses for identifying neonatal pain. These findings will inform the development of a continuous, unbiased, brain-based, nurse-in-the-loop Pain Recognition Automated Monitoring System (PRAMS) for neonates and infants. [ABSTRACT FROM AUTHOR]

Exposure to repetitive painful procedures in the neonatal intensive care unit results in long‐lasting effects, especially visible after a "second hit" in adulthood. As the nociceptive system and the hypothalamic–pituitary–adrenal (HPA) axis interact and are vulnerable in early life, repetitive painful procedures in neonates may affect later‐life HPA axis reactivity. The first aim of the present study was to investigate the effects of repetitive neonatal procedural pain on plasma corticosterone levels after mild acute stress (MAS) in young adult rats. Second, the study examined if MAS acts as a "second hit" and affects mechanical sensitivity. Fifty‐two rats were either needle pricked four times a day, disturbed, or left undisturbed during the first neonatal week. At 8 weeks, the animals were subjected to MAS, and plasma was collected before (t0), after MAS (t20), and at recovery (t60). Corticosterone levels were analyzed using an enzyme‐linked immunosorbent assay, and mechanical sensitivity was assessed with von Frey filaments. Results demonstrate that repetitive neonatal procedural pain reduces stress‐induced plasma corticosterone increase after MAS only in young adult females and not in males. Furthermore, MAS does not affect mechanical sensitivity in young adult rats. Altogether, the results suggest an age‐ and sex‐dependent effect of repetitive neonatal procedural pain on HPA axis reprogramming. [ABSTRACT FROM AUTHOR]

This research was planned to determine the effect of breastfeeding on newborns' behavioral pain and comfort scores during heel blood collection. A pretest/posttest experimental-control group design was used. The research was conducted between August 2021 and June 2022. A total of 50 newborns, including 25 in each of the experimental and control groups, were included in the study. An Infant Descriptive Information Form, the COMFORTneo Behaviour Scale, the NIPS-Neonatal Infant Pain Scale, and the LATCH Breastfeeding Diagnosis and Assessment Tool were used in the study. The comfort behaviors and pain scores of infants in the experimental and control groups were evaluated during the heel blood collection process. The comparison of the comfort behaviors (comfort, pain, and distress), differences between pretest-posttest scores on the NIPPS pain score, and crying duration of the newborns in the experimental and control groups indicated a significant difference (p 0.05). The intra-group differences between the mean pretest and posttest scores of both the intervention and control groups were found to be statistically significant (p 0.05). Breastfeeding is an important nursing intervention for reducing procedural pain in newborns. The breastfeeding method reduces pain and distress and increases comfort for newborns during the heel blood collection process. Breastfeeding is an important nursing intervention for reducing procedural pain in newborns. The breastfeeding method reduces the pain and distress of the newborn during the heel blood collection process and increases comfort. Neonatal nurses can diversify the effectiveness of non-pharmacological methods in painful interventions by evaluating them with appropriate tools [ABSTRACT FROM AUTHOR]

Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions. Methods: A web-based survey was distributed to neonatal units worldwide. Results: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always. Conclusions: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries.

Preterm infants often undergo painful medical procedures, and mitigating their pain remains a critical challenge in neonatal care. This manuscript explores the innovative approach of sensory stimulation as a promising horizon in alleviating preterm pain. Through a comprehensive review of existing literature, we examine the current understanding of pain perception in preterm infants and the limitations of conventional pain management strategies. The manuscript deals with the neurobiological underpinnings of pain in preterm neonates, shedding light on the unique challenges posed by their immature nervous systems. Drawing on recent advances in sensory science, we propose a paradigm shift toward personalized sensory stimulation interventions tailored to the developmental stage of preterm infants. A critical analysis of studies investigating the efficacy of various sensory modalities, including music therapy, tactile stimulation, and olfactory interventions, is presented. The manuscript also explores the potential integration of technological innovations, such as virtual reality, into neonatal care to enhance the positive impact of sensory stimulation on pain modulation. By fostering a deeper understanding of the neurobiological basis of pain in preterm neonates and exploring innovative interventions, this work aims to contribute to the ongoing efforts to improve the quality of care for this vulnerable population. [ABSTRACT FROM AUTHOR]

Cassandra Hoffmann,1 Angela Snow,2 Celine Chedid,3 Carol Abi Shadid,3 Eiichi A Miyasaka4 1Pediatric Anesthesiology, Akron Children’s Hospital, Akron, OH, USA; 2Pediatric Anesthesiology, Nemours Children’s Hospital, Wilmington, DE, USA; 3Pediatric Anesthesiology, University Hospitals Rainbow Babies and Children’s Hospital, Cleveland, OH, USA; 4Pediatric Surgery, University Hospitals Rainbow Babies and Children’s Hospital, Cleveland, OH, USACorrespondence: Eiichi A Miyasaka, Pediatric Surgery, University Hospitals Rainbow Babies and Children’s Hospital, 11100 Euclid Ave, MAC 1000, Cleveland, OH, 44106, USA, Tel +1 216-844-3015, Fax +1 216-844-8647, Email eiichi.miyasaka@uhhospitals.orgPurpose: Neonates present unique challenges for pediatric surgical teams. To optimize outcomes, it is imperative to standardize perioperative care by using early extubation and multimodal analgesic techniques. The quadratus lumborum (QL) block provides longer duration and superior pain relief than other single-injection abdominal fascial plane techniques. The purpose of this case series was to report our initial experience with QL blocks in neonatal patients treated with intestinal ERAS.Patients and Methods: Ten neonates requiring intestinal surgery at a single tertiary care center who received QL blocks between December 2019 and April 2022 for enhanced recovery were studied. Bilateral QL blocks were performed with 0.5 mL/kg of 0.25% ropivacaine per side with an adjuvant of 1 mcg/kg of dexmedetomidine.Results: Gestational age at birth ranged from 32.2 to 41 weeks. The median age, weight, and American Society of Anesthesiologists (ASA) score at the time of surgery was 5 days [range 7.5 hours, 60 days], 2.84 kg [range 1.5, 4.5], and 3, respectively. Bilateral QL blocks were performed without complications in all patients. Two patients were outside the neonatal range from birth to surgery, but were under 42 weeks gestational age when corrected for prematurity. All patients were extubated with well-controlled pain, and no patient required reintubation within the first 24 hours. Postoperatively, median cumulative morphine equivalents were 0.16 mg/kg [range 0, 0.79] and six patients received scheduled acetaminophen. Morphine (0.1 mg/kg) was administered to patients with a modified neonatal infant pain scale (NIPS) score greater than or equal to 4, and pain was reassessed 1 hour after administration (Appendix).Conclusion: When developing intestinal ERAS protocols, Bilateral QL blocks may be considered for postoperative analgesia in the neonatal population. Further prospective studies are required to validate this approach in neonates.Keywords: neonatal pain, neonatal regional anesthesia, early neonatal extubation, neonatal intestinal surgery, neonatal enhanced recovery

BackgroundNeonates admitted to neonatal intensive care units experience an average of 8–17 moderate to severe painful procedures per day. Because neonates lack the cognitive capacity to express their pain's location or severity, they are very dependent on healthcare providers to recognize, assess, and manage their pain. The health and development of newborns are negatively impacted by persistent or untreated pain experienced early in life. Therefore, studying neonatal pain management practices and associated factors in healthcare is critical to tackling workforce problems, enhancing neonatal care, and lowering the long-term health impacts of neonates.MethodFrom January 1 to 30, 2023, a facility-based cross-sectional study design was used at six public hospitals in the Somali region of Ethiopia. A total of 336 healthcare providers enrolled using a simple random sample technique. A self-administered, structured questionnaire was utilized to collect the data. The analyses used bivariate and multivariate logistic regression. To find the association between the outcome and predictor factors, the odd ratio and the 95% CI were computed.ResultThe study revealed that 35.4% [95% CI 30.4%–40.5%] of respondents reported that they had good neonatal pain management practices. Ever having undergone training in neonatal pain assessment and management [AOR = 2.26 (95% CI 1.259, 4.07)], availability of pain assessment tools [AOR = 3.05 (95% CI 1.249, 7.469)], and having a favorable attitude toward neonatal pain management practice [AOR = 3.71 (95% CI 1.525, 9.035)] were found to be factors with a significant association with neonatal pain management practice.ConclusionBased on the study's findings, there is a low level of neonatal pain management practice among healthcare providers in the Somali region. The study emphasizes the significance of having access to pain assessment tools and the requirement for healthcare professionals to get training on neonatal pain assessment and management.

Background: Newborn babies in the Neonatal Intensive Care Units (NICU) and Newborn Units (NBUs) undergo several procedures that cause a significant amount of pain. Nurses play an essential role in the implementation of pain assessment and management measures in neonates. However, while it remains widely known that nurses play an important role in neonatal pain management, nurses’ practices on the management of pain in neonates admitted in Newborn care units have not been widely published within the nursing science. Objectives: To evaluate neonatal pain management practices among nurses working in newborn units in Nyanza and Western Kenya. Methods: A descriptive cross-sectional study using qualitative and quantitative approaches was used targeting 89 nurses. The collection of data was done through semi-structured, self-administered questionnaires with both closed and open –ended questions. Qualitative data was collected through in-depth interviews. Data obtained was analyzed using the statistical package for social science (SPSS) version 22.0 software. The study assumed a confidence level of 95% and a (p) value equal to or less than 0.05 was considered significant. Qualitative data was analyzed through logic checks to understand the emerging themes. Descriptive statistical analysis was done using frequencies, percentage and means. Results: The study established that a small percentage of the nurses practiced pain management in neonates through use of non-pharmacologic (34.8%) and pharmacologic (28.1%) strategies. The commonly used non-pharmacologic strategies include changing of nappies (71.9%) and repositioning (68.5). Pain assessment was however seldom done. Conclusion: Following the results, the study concluded that nurses practice pain management in neonates by implementing non-pharmacological and pharmacological strategies. The commonly used pain management strategy in neonates is utilization of non-pharmacological strategies such as change of nappies repositioning and kangaroo mother care. However, gaps exist in knowledge and competency on neonatal pain management aspects and practice. The study therefore recommended enhancement of awareness on aspects of neonatal pain among nurses to facilitate improved pain management practices in neonates. Further strengthening of nurses’ knowledge and skills on pain management in neonates through attending scheduled short courses, workshops and on job training is recommended.

Neonatal pain is a problem that is easily overlooked. According to the status quo of neonatal pain management, commonly 9 scales are used for evaluation of neonatal pain; details of the specific indicators, such as the applicable neonatal gestational age range, score, and the type of pain, for the domestic references are provided so as to provide reference for the proper evaluation and standardized management of neonatal pain, as well as to promote the management level of neonatal pain.

Non-nutritive sucking and oral uptake of glucose 25% are often non-pharmacological methods used to manage procedural pain in newborns. Aim: To compare the effect of using non-nutritive suction (NNS) and Sol.Glucosae 25% for reducing/eliminating neonatal pain due to heel prick. Material and methods: Term infants were studied: group (A), NNS, n = 40, and group (B) oral uptake of Sol.Glucosae 25%, n = 40. The severity of procedural pain was assessed using the Neonatal Facial Coding System (NFCS) scale: 30 seconds before the procedure, at the 30th second and at the 5th minute after the procedure. Physiological pain markers were monitored at these intervals: respiratory, heart rate, transcutaneous saturation (tSpO2), arterial blood pressure. Results and Discussion: Newborns in a group (B) had a lower evaluation at the 5th minute compared to those treated with non-nutritive suckling(A). There are significant differences in heart rate, breathing frequency and before the procedure. The intake of Sol. Glucose 25% compared to NNS causes a higher heart rate and a decrease in at the 30th second after the painful procedure. In contrast to the heart rate, for respiratory rate and tSpO2 at 5th min. we reported lower than the norms in both groups A and B. Conclusion: Unlike NNS, glucose intake eliminates pain within 5 minutes after a heel prick. Excluding arterial blood pressure, all other physiological pain markers undergo changes before the procedure but not after it.

Background: Objective assessment tools should standardize and reflect nurses' expert assessments. The Neonatal Pain, Agitation, and Sedation Scale (N-PASS) and the Neonatal Infant Pain Scale (NIPS) are valid measures of pain. The N-PASS also provides a sedation subscale. Purpose: The objective of this study was to determine N-PASS clinical validity and utility by evaluating agreement of N-PASS scores with bedside nurses' assessments of pain/agitation and sedation in a 64-bed tertiary neonatal intensive care unit. Methods: Fifteen bedside nurses trained to use the N-PASS and the NIPS prospectively completed 202 pain/agitation and sedation assessments from a convenience sample of 88 infants, including chronically ventilated, medically fragile infants. N-PASS and NIPS scores were obtained simultaneously but independently of nurse investigators. Bedside nurses also made recommendations about infants' pain and sedation management. Results: There was moderate agreement between N-PASS pain scores and nurses' recommendations (κ= 0.52), very strong agreement between N-PASS sedation scores and nurses' recommendations (κ= 0.99), and very strong associations between N-PASS pain and NIPS scores (P <.001). Bedside nurse and independent investigator interrater reliability was good for N-PASS pain and NIPS scores (intraclass correlation coefficient [ICC] = 0.83, ICC = 0.85) and excellent for N-PASS sedation (ICC = 0.94). During 93% of assessments, bedside nurses reported that the N-PASS reflected the level of infant sedation well or very well. Implications for Practice and Research: The N-PASS provides an easy-to-use, valid, and reliable objective measure of pain and sedation that reflects nurses' assessments. Additional studies using the N-PASS are needed to verify results and the influence of the N-PASS on pain and sedation management for medically fragile infants with chronic medical conditions. [ABSTRACT FROM AUTHOR]

Aim: This study aims to characterise current pain management practices in extremely preterm infants (gestational age less than or equal to 28 weeks) admitted to neonatal intensive care unit (NICU). Methods: Retrospective audit pertaining to patient characteristics, as well as minor painful procedures (MPP), pain mitigation and pain scoring in 25 extremely preterm infants admitted to a tertiary NICU in 2016 over the first 14 days of NICU admission. Opportunities to bundle MPP were identified according to pre‐specified criteria. Bayley Scales of Infant Development, Third Edition (BSID‐III) cognitive, language and motor composite scores were available from the neurodevelopmental follow‐up clinic at 12‐ and 24‐months of corrected age. Linear mixed methods regression was used to examine for correlation between increased exposure to MPP and BSID‐III scores at follow‐up. Results: Extremely preterm infants underwent an average of 11.24 ± 4.12 MPP per day for the first 14 days of NICU admission. Opportunities to bundle MPP were missed 75.98% (408/537) of the time; most of these were invasive blood collections. A total of 12.2% (481/3933) of MPP occurred within 4 h of pharmacological or non‐pharmacological pain mitigation. BSID‐III motor composite score was associated with an 11.75 (95% confidence interval 1.99, 21.27) decrease in patients experiencing more than or equal to the third quartile of MPP in the 14 days post‐NICU admission (P = 0.0329, n = 42). Association was not found for BSID‐III cognitive and language composite scores. Conclusions: There is readily scope for quality improvement initiatives to reduce harm in extremely preterm infants admitted to NICU. [ABSTRACT FROM AUTHOR]

Infants might be exposed to pain during their admissions in the neonatal intensive care unit [NICU], both from their underlying conditions and several invasive procedures required during their stay. Considering the particularities of this population, recognition and adequate management of pain continues to be a challenge for neonatologists and investigators. Diverse therapies are available for treatment, including non-pharmacological pain management measures and pharmacological agents (sucrose, opioids, midazolam, acetaminophen, topical agents...) and research continues. In recent years one of the most promising drugs for analgesia has been dexmedetomidine, an alpha-2 adrenergic receptor agonist. It has shown a promising efficacy and safety profile as it produces anxiolysis, sedation and analgesia without respiratory depression. Moreover, studies have shown a neuroprotective role in animal models which could be beneficial to neonatal population, especially in preterm newborns. Side effects of this therapy are mainly cardiovascular, but in most studies published, those were not severe and did not require specific therapeutic measures for their resolution. The main objective of this article is to summarize the existing literature on neonatal pain management strategies available and review the efficacy of dexmedetomidine as a new therapy with increasing use in the NICU. [ABSTRACT FROM AUTHOR]

In this article, we introduce a new neonatal facial expression database for pain analysis. This database, called facial expression of neonatal pain (FENP), contains 11,000 neonatal facial expression images associated with 106 Chinese neonates from two children's hospitals, i.e., the Children's Hospital Affiliated to Nanjing Medical University and Second Affiliated Hospital Affiliated to Nanjing Medical University in China. The facial expression images cover four categories of facial expressions, i.e., severe pain expression, mild pain expression, crying expression and calmness expression, where each category contains 2750 neonatal facial expression images. Based on this database, we also investigate the pain facial expression recognition problem using several state-of-the-art facial expression features and expression recognition methods, such as Gabor+SVM, LBP+SVM, HOG+SVM, LBP+HOG+SVM, and several Convolutional Neural Network (CNN) methods (including AlexNet, VGGNet, GoogLeNet, ResNet and DenseNet). The experimental results indicate that the proposed neonatal pain facial expression database is very suitable for the study of both neonatal pain and facial expression recognition. Moreover, the FENP database is publicly available after signing a license agreement (the users can contact Jingjie Yan (yanjingjie@njupt.edu.cn), Guanming Lu (lugm@njupt.edu.cn)) or Xiaonan Li (xnli@njmu.edu.cn). [ABSTRACT FROM AUTHOR]

Aim: Non‐pharmacological methods are commonly used to reduce the procedural pain in newborns. In this open label, randomised control trial, we studied the pain‐reducing effect of kangaroo mother care (KMC) during orogastric tube insertion. Methods: Newborns, with birthweight 1500–2499 g and admitted to nursery, were randomised into control (no‐KMC) or intervention (KMC) arms. In intervention arm, KMC was given for 60 min before and after the procedure. Premature Infant Pain Profile‐Revised (PIPP‐R) score was used to assess the pain response and the pain severity was graded as minimal or no pain (≤6), mild‐to‐moderate (7–12) and severe (>12). The PIPP‐R scoring was done before, during and at 3‐ and 15‐min after procedure. Change in PIPP‐R scores from baseline was calculated. Results: Newborns included in no‐KMC (n = 40) or KMC (n = 40) arms were comparable for major confounders (P > 0.05). Pre‐procedural pain scores were comparable (P = 0.72). Pain scores measured during and after procedure were significantly higher in no‐KMC group than KMC arm. The KMC reduced the pain score by 39%, 32% and 30% during and at 3‐ and 15‐min after procedure respectively as compared to control (P < 0.01). The increase in PIPP‐R score from pre‐procedural level was 40%, 35% and 31% lower in KMC than no‐KMC arm (P < 0.01). A greater proportion of newborns had significantly less severe grades of pain in the intervention arm compared to the no‐KMC arm (P < 0.01). Conclusion: Orogastric tube placement is a painful procedure. KMC significantly reduces periprocedural pain and its effect continues for at least 15 min after the procedure. [ABSTRACT FROM AUTHOR]

Introduction: The most important purpose in neonatal pain management is to minimize the pain felt by newborns and to help the newborn cope with pain. This study planned to examine the effects of two non-pharmacological methods, using pacifiers or maternal holding, on neonates’ pain admitted to the outpatient clinic (OC) and hospitalized in the Neonatal Intensive Care Unit (NICU). Material and Methods: Ninety newborns (30 used pacifiers, 30 maternal holding,30 control) who applied to the OC and 60 newborns (30 used pacifiers, 30 control) admitted to the NICU were prospectively included in this study. The Neonatal Infant Pain Scale (NIPS) was used to evaluate behavioral responses to pain perception. Physiological parameters of newborns and their durations of crying were also evaluated. Results: When the NIPS scores were analyzed in OC group during and after the procedure, the lowest score was found in the group using pacifiers (p lt;0.001). As for the NICU patients, both during and after the procedure, NIPS scores were found to be significantly lower in the pacifier users (p lt;0.001). It was observed that giving pacifiers and mathernal holding had positive effects on physiological parameters and duration of crying in OC patients (p lt;0.05). No significant difference in the NIPS score was found between OC and NICU group. Conclusion: This study showed that giving pacifiers and maternal holding during the procedure of blood sampling decreased the NIPS score, restored the changes in physiological parameters and decreased the duration of crying.

BackgroundThe assessment and management of neonatal pain is crucial for the development and wellbeing of vulnerable infants. Specifically, neonatal pain is associated with adverse health outcomes but is often under-identified and therefore under-treated. Neonatal stress may be misinterpreted as pain and may therefore be treated inappropriately. The assessment of neonatal pain is complicated by the non-verbal status of patients, age-dependent variation in pain responses, limited education on identifying pain in premature infants, and the clinical utility of existing tools.ObjectiveWe review research surrounding neonatal pain assessment scales currently in use to assess neonatal pain in the neonatal intensive care unit.MethodsWe performed a systematic review of original research using PRISMA guidelines for literature published between 2016 and 2021 using the key words “neonatal pain assessment” in the databases Web of Science, PubMed, and CINAHL. Fifteen articles remained after review, duplicate, irrelevant, or low-quality articles were eliminated.ResultsWe found research evaluating 13 neonatal pain scales. Important measurement categories include behavioral parameters, physiological parameters, continuous pain, acute pain, chronic pain, and the ability to distinguish between pain and stress. Provider education, inter-rater reliability and ease of use are important factors that contribute to an assessment tool's success. Each scale studied had strengths and limitations that aided or hindered its use for measuring neonatal pain in the neonatal intensive care unit, but no scale excelled in all areas identified as important for reliably identifying and measuring pain in this vulnerable population.ConclusionA more comprehensive neonatal pain assessment tool and more provider education on differences in pain signals in premature neonates may be needed to increase the clinical utility of pain scales that address the different aspects of neonatal pain.

Abstract Osteogenesis imperfecta (OI) is a rare genetic heterogeneous disorder that causes increased bone fragility and recurrent fractures. For infants with OI and diffuse fractures, pain management, which is nuanced and specific for this population, is of the utmost importance to their neonatal care. Through experience at our center, we have developed a standard approach that has been successful in optimizing survival for these infants during this tenuous period. In this paper, we outline our multidisciplinary approach to pain management for infants with moderate to severe OI during the neonatal period, with emphasis on promotion of fracture healing and adequate pain control.

It is necessary to treat neonatal pain because it may have short- and long-term adverse effects. Frenotomy is a painful procedure where sucking, a common strategy to relieve pain, cannot be used because the technique is performed on the tongue. In a previous randomized clinical trial, we demonstrated that inhaled lavender essential oil (LEO) reduced the signs of pain during neonatal frenotomy. We aimed to find out whether inhaled vanilla essential oil (VEO) is more effective in reducing pain during frenotomy than LEO. Randomized clinical trial with neonates who underwent a frenotomy for type 3 tongue-ties between May and October 2021. Pain was assessed using pre and post-procedure heart rate (HR) and oxygen saturation (SatO2), crying time, and NIPS score. Neonates were randomized into "experimental" and "control" group. In both groups, we performed swaddling, administered oral sucrose, and let the newborn suck for 2 min. We placed a gauze pad with one drop of LEO (control group) or of VEO (experimental group) under the neonate's nose for 2 min prior to and during the frenotomy. We enrolled 142 neonates (71 per group). Both groups showed similar NIPS scores (2.02 vs 2.38) and crying times (15.3 vs 18.7 s). We observed no differences in HR increase or in SatO2 decrease between both groups. We observed no side effects in either of the groups.Conclusions: We observed no appreciable difference between LEO and VEO; therefore, we cannot conclude which of them was more effective in treating pain in neonates who underwent a frenotomy.Trial Registration:  This clinical trial is registered with www.Clinicaltrials: gov with NCT04867824.What Is Known: • Pain management is one of the most important goals of neonatal care as it can have long-term neurodevelopmental effects. • Lavender essential oil can help relieve pain due to its sedative, antispasmodic, and anticolic properties.What Is New: • Lavender and vanilla essential oils are safe, beneficial, easy to use, and cheap in relieving pain in neonates who undergo a frenotomy for type 3 tongue-ties. [ABSTRACT FROM AUTHOR]

BackgroundRetinopathy of prematurity (ROP) ophthalmologic examinations cause stress and pain. Infants’ stress and pain can be measured non-invasively using skin conductance (SC) and high frequency heart rate variability (HF-HRV), reflecting sympathetic-mediated sweating and parasympathetic activity, respectively.ObjectivesTo test the utility of SC to detect sympathetic activation during ROP examination, and the contribution of HF-HRV to predict stability post-examination.MethodsIn this prospective, single center study, we measured SC continuously pre-, during, and post-examination, and HRV at 24 h pre-ROP examination. Clinical data included stability [apneas, bradycardias, and desaturations (A/B/Ds)], and interventions post-examination.ResultsSC increased 56% above baseline during ROP examination (p = 0.001) and remained elevated post-examination (p = 0.02). Post-hoc analysis showed higher illness acuity, represented by need for respiratory support, was associated with lower HF-HRV at 24 h pre-ROP examination (p = 0.001). Linear regression indicated lower HF-HRV at 24 h pre-examination contributed to the need for higher intervention (i.e., stimulation to breathe, oxygen support) particularly among infants with higher illness acuity [F(1, 15) = 5.05, p = 0.04; β = −1.33, p = 0.04].ConclusionROP examination induced a 2-fold increase in sympathetic activation which remained above baseline in recovery. Also, we propose that the low parasympathetic tone associated with autonomic imbalance contributes to instability and need for higher intervention to assure stabilization with A/B/D events. Our findings provide insight into the underestimation of adverse events associated with ROP examination and identification of infants who may be more vulnerable to potential sequelae following ROP examinations.

Background: Accurate neonatal pain assessment (NPA) is the key to neonatal pain management, yet it is a challenging task for medical staff. This study aimed to analyze the clinical practicability of the artificial intelligence based NPA (AI-NPA) tool for real-world blood sampling. Method: We performed a prospective study to analyze the consistency of the NPA results given by a self-developed automated NPA system and nurses' on-site NPAs (OS-NPAs) for 232 newborns during blood sampling in neonatal wards, where the neonatal infant pain scale (NIPS) was used for evaluation. Spearman correlation analysis and the degree of agreement of the pain score and pain grade derived by the NIPS were applied for statistical analysis. Results: Taking the OS-NPA results as the gold standard, the accuracies of the NIPS pain score and pain grade given by the automated NPA system were 88.79% and 95.25%, with kappa values of 0.92 and 0.90 (p < 0.001), respectively. Conclusion: The results of the automated NPA system for real-world neonatal blood sampling are highly consistent with the results of the OS-NPA. Considering the great advantages of automated NPA systems in repeatability, efficiency, and cost, it is worth popularizing the AI technique in NPA for precise and efficient neonatal pain management. [ABSTRACT FROM AUTHOR]

The objective of this systematic review was to identify and describe the psychometric properties of neonatal pain scales that were translated into Brazilian Portuguese and to verify the methodological quality of these translation, transcultural adaptations and validation. The present study is a systematic review. A systematic search in the literature included studies of development, validation, and transcultural adaptation of neonatal pain scales to Brazilian Portuguese. The instruments must have been developed for health care professionals to evaluate neonatal pain and stress in full-term and preterm newborns. The search strategy was conducted in PubMed, Web of Science, Scopus, and Scielo databases following The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). A total of 1,479 publications were identified and 5 fulfilled the inclusion criteria, with 4 instruments evaluated. For the methodological quality analysis of the measurement properties of the instruments the Consensus-based Standards for Health Measurement Instruments (COSMIN) Risk of Bias checklist was used. The psychometric properties verified were internal consistency, content validity, reliability, and construct validity. Three instruments reviewed were inadequate and one was doubtful. The neonatal pain scales wich were cross culturally adapted to Brazilian Portuguese were shown to be of low methodological quality based on COSMIM checklist. Caution should be considered for clinical decisions about pain management judgment coming from these instruments. [ABSTRACT FROM AUTHOR]

Excessive noxious stimulation during the critical neonatal period impacts the nociceptive network lasting into adulthood. As descending serotonergic projections from the rostral ventromedial medulla (RVM) to the spinal dorsal horn develop postnatally, this study aims to investigate the long-term effect of repetitive neonatal procedural pain on the descending serotonergic RVM--spinal dorsal horn network. A well-established rat model of repetitive noxious procedures is used in which neonatal rats received four noxious needle pricks or tactile stimulation with a cotton swab per day in the left hind paw from day of birth to post-natal Day 7. Control animals were left undisturbed. When animals reached adulthood, tissue was collected for quantitative immunohistochemical analysis of serotonin (5-hydroxytryptamine, 5-HT) in the RVM and spinal dorsal horn. Both repetitive noxious and tactile procedures in the neonate decreased the 5-HT staining intensity in the adult ipsilateral but not contralateral spinal dorsal horn. Repetitive neonatal noxious procedures resulted in an increased area covered with 5-HT staining in the adult RVM ipsilateral to the side of injury, whereas repetitive neonatal tactile stimulation resulted in increased 5-HT staining intensity in both the ipsi- and contralateral RVM. The number of 5-HT cells in adult RVM is unaffected by neonatal conditions. This detailed anatomical study shows that not only neonatal noxious procedures but also repetitive tactile procedures result in long-lasting anatomical changes of the descending serotonergic system within the RVM and spinal dorsal horn. Future studies should investigate whether these anatomical changes translate to functional differences in descending serotonergic modulation after neonatal adverse experiences. [ABSTRACT FROM AUTHOR]

Background: Neonatal pain may affect long-term neurodevelopment and must be treated. Frenotomy is a painful procedure wherein a common strategy to relieve pain (sucking) cannot be used because the technique is performed on the tongue. Lavender essential oil (LEO) has sedative and antispasmodic properties and has been successfully used to treat pain during heel puncture and vaccination. Our aim was to demonstrate if the use of inhaled LEO is effective in reducing pain during frenotomy in healthy, full-term neonates. Methods: We conducted a randomized clinical trial in neonates who underwent a frenotomy between August 2020 and April 2021. We assessed pain using pre and post-procedure heart rate and oxygen saturation, crying time and Neonatal Infant Pain Scale (NIPS) score. Patients with type 3 tongue tie were randomized into the "experimental group" and "control group". In both groups, we performed swaddling, administered oral sucrose, and let the newborn suck for two minutes. In the experimental group, we also placed a gauze pad with one drop of LEO under the neonate's nose for two minutes prior to and during the frenotomy. Results: We enrolled 142 patients (71 per group). The experimental group showed significantly lower NIPS scores (1.88 vs 2.92) and cried almost half the amount of time (14.8 vs. 24.6 seconds, P = 0.006). Comparing with the control group, we observed no side effects in either of the groups. Conclusions: We observed a significant decrease in crying time and lower NIPS scores in the neonates who received inhaled LEO and underwent a frenotomy for type 3 tongue-ties. Thus, we recommend using inhaled LEO during neonatal frenotomies. [ABSTRACT FROM AUTHOR]

Objectives: By nature, the neonatal intensive care unit (NICU) environment is stressful for both infants and mothers. This study aimed to explore and quantify the severity of early life stressors in premature infants admitted to the NICU and evaluate the effect of cumulative neonatal stressors on maternal mental health.Methods: This cross-sectional study included 100 preterm infants admitted to the NICU for at least 10 days. Daily experiences with painful/stressful procedures for 10 days were determined using the Neonatal Infant Stressor Scale. The included mothers were assessed for their psychological well-being 1 week after NICU admission using the Parental Stressor Scale: NICU and Edinburgh Postnatal Depression Scale.Results: During the first 10 days of NICU admission, preterm infants experienced an average of 350.76 ± 84.43 acute procedures and an average of 44.84 ± 11.12 cumulative hours of chronic events, with the highest scores recorded on first 3 days of admission. Although intravenous flushing for patency was the most frequent acute procedure, blood gas sampling was the most painful. Forty-five percent of the mothers showed significant depressive symptoms, with the maternal role alteration reported as the most stressful experience, especially for young and new mothers (p < .001). The cumulative stressors experienced by infants were significantly associated with elevated maternal perception of psychological maladjustment (p < .001).Conclusion: This study confirmed that the NICU environment is stressful for both infants and mothers, with the total cumulative stressors experienced by preemies in the NICU having an negative impact on maternal mental health. [ABSTRACT FROM AUTHOR]

Neonatal intensive care treatment, including frequently performed painful procedures and administration of analgesic drugs, can have different effects on the neurodevelopment. This systematic review and meta-analysis aimed to investigate the influence of pain, opiate administration, and pre-emptive opiate administration on pain threshold in animal studies in rodents, which had a brain development corresponding to preterm and term infants. A systematic literature search of electronic data bases including CENTRAL (OVID), CINAHL (EBSCO), Embase.com, Medline (OVID), Web of Science, and PsycInfo (OVID) was conducted. A total of 42 studies examining the effect of pain (n = 38), opiate administration (n = 9), and opiate administration prior to a painful event (n = 5) in rodents were included in this analysis. The results revealed that pain (g = 0.42, 95%CI 0.16–0.67, p = 0.001) increased pain threshold leading to hypoalgesia. Pre-emptive opiate administration had the opposite effect, lowering pain threshold, when compared to pain without prior treatment (g = −1.79, 95%CI −2.71–0.86, p = 0.0001). Differences were found in the meta regression for type of stimulus (thermal: g = 0.66, 95%CI 0.26–1.07, p = 0.001; vs. mechanical: g = 0.13, 95%CI −0.98–1.25, p = 0.81) and gestational age (b = −1.85, SE = 0.82, p = 0.027). In addition, meta regression indicated an association between higher pain thresholds and the amount of cumulative pain events (b = 0.06, SE = 0.03, p = 0.05) as well as severity of pain events (b = 0.94, SE = 0.28, p = 0.001). Neonatal exposure to pain results in higher pain thresholds. However, caution is warranted in extrapolating these findings directly to premature infants. Further research is warranted to validate similar effects in clinical contexts and inform evidence-based practices in neonatal care. • Neonatal pain exposure had a measurable negative effect on pain thresholds in rodents. • Differences were found in the meta regression for type of stimulus (thermal/mechanical) and gestational age (term/preterm). • Higher pain thresholds were associated with the amount of cumulative pain events as well as the severity of pain events. [ABSTRACT FROM AUTHOR]

Neonatal pain management is an important issue which should have great attention. More and more researches have proved that neonates can feel pain when undergoes painful procedures such as vaccination, heel stick, and so on, and it will result in short-term and long-term outcomes. So it is very important to manage neonatal pain. This article summarized some non-pharmaceutical interventions, including sucrose or glucose, non-nutritional sucking (NNS), breastfeeding, facilitated tucking (FT), kangaroo mother care (KMC), swaddling, heel warming, sensorial saturation (SS), and music therapy, which showed obvious effects for neonatal pain. In addition, this article summarized the progress of neonatal pain intervention in various countries and showed that many countries have not paid enough attention to this problem, while some countries have carried out promotion programs for neonatal pain management which give some clinical enlightenment to our country that we need to pay more attention to this problem.

Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive signals in neonates. The current study aims to attenuate acute and long-term hypersensitivity associated with neonatal procedural pain using ondansetron (a 5-HT3 antagonist) and buspirone (a 5-HT1a agonist) in a well-established rat model of repetitive needle pricking. Sprague-Dawley rat pups of both sexes received ondansetron (3 mg/kg), buspirone (3 mg/kg) or saline prior to repetitive needle pricks into the left hind-paw from postnatal day 0–7. Control animals received tactile stimulation or were left undisturbed. Acute, long-term, and post-operative mechanical sensitivity as well as adult anxiety were assessed. Neonatal 5-HT1a receptor agonism completely reverses acute hypersensitivity from P0-7. The increased duration of postoperative hypersensitivity after re-injury in adulthood is abolished by 5-HT3 receptor antagonism during neonatal repetitive needle pricking, without affecting baseline sensitivity. Moreover, 5-HT1a and 5-HT3 receptor modulation decreases adult state anxiety. Altogether, our data suggests that targeted pharmacological treatment based on the modulation of spinal serotonergic network via the 5-HT1a and 5-HT3 receptors in neonates may be of use in treatment of neonatal procedural pain and its long-term consequences. This may result in a new mechanism-based therapeutic venue in treatment of procedural pain in human neonates.

Osteogenesis imperfecta (OI) is a rare genetic heterogeneous disorder that causes increased bone fragility and recurrent fractures. For infants with OI and diffuse fractures, pain management, which is nuanced and specific for this population, is of the utmost importance to their neonatal care. Through experience at our center, we have developed a standard approach that has been successful in optimizing survival for these infants during this tenuous period. In this paper, we outline our multidisciplinary approach to pain management for infants with moderate to severe OI during the neonatal period, with emphasis on promotion of fracture healing and adequate pain control. [ABSTRACT FROM AUTHOR]

Background: Premature neonates receive a large number of painful procedures during their stay in the neonatal intensive care unit (NICU). However, there are many other processes that happen in the NICU, which may not be considered painful but can cause discomfort and/or stress to the neonate. Method: Pain profile during routine procedures in NICU was assessed using the premature infant pain profile (PIPP) score. Neonates of gestational age> 26 weeks, less than 7 days old and admitted for less than 7 days in the NICU were included. Results: A total of 662 procedures were observed in 132 (78 M, 54 F) neonates. The mean (SD) age of the neonates was 2.4 (1.8) days and the mean (SD) birth weight was 2.3 (0.6) kg. 63 (54.5%) were of low birth weight (LBW), 85 (64.39%) were full term. High PIPP score was noted in blood sampling, heel prick, suction, and weight measurement. Significant differences were observed in the PIPP score during blood sampling and suction across gender. Some ordinary and non-stressful procedures also scored very high on the PIPP scale. Conclusions: The validity of PIPP needs to be reexamined. Our understanding of pain during routine procedures may need to be revisited.

Infants might be exposed to pain during their admissions in the neonatal intensive care unit [NICU], both from their underlying conditions and several invasive procedures required during their stay. Considering the particularities of this population, recognition and adequate management of pain continues to be a challenge for neonatologists and investigators. Diverse therapies are available for treatment, including non-pharmacological pain management measures and pharmacological agents (sucrose, opioids, midazolam, acetaminophen, topical agents…) and research continues. In recent years one of the most promising drugs for analgesia has been dexmedetomidine, an alpha-2 adrenergic receptor agonist. It has shown a promising efficacy and safety profile as it produces anxiolysis, sedation and analgesia without respiratory depression. Moreover, studies have shown a neuroprotective role in animal models which could be beneficial to neonatal population, especially in preterm newborns. Side effects of this therapy are mainly cardiovascular, but in most studies published, those were not severe and did not require specific therapeutic measures for their resolution. The main objective of this article is to summarize the existing literature on neonatal pain management strategies available and review the efficacy of dexmedetomidine as a new therapy with increasing use in the NICU.

Farm animals routinely undergo painful husbandry procedures early in life, including disbudding and castration in calves and goat kids, tail docking and castration in piglets and lambs, and beak trimming in chicks. In rodents, inflammatory events soon after birth, when physiological systems are developing and sensitive to perturbation, can profoundly alter phenotypic outcomes later in life. This review summarizes the current state of research on long-term phenotypic consequences of neonatal painful procedures in rodents and farm animals, and discusses the implications for farm animal welfare. Rodents exposed to early life inflammation show a hypo-/hyper-responsive profile to pain-, fear-, and anxiety-inducing stimuli, manifesting as an initial attenuation in responses that transitions into hyperresponsivity with increasing age or cumulative stress. Neonatal inflammation also predisposes rodents to cognitive, social, and reproductive deficits, and there is some evidence that adverse effects may be passed to offspring. The outcomes of neonatal inflammation are modulated by injury etiology, age at the time of injury and time of testing, sex, pain management, and rearing environment. Equivalent research examining long-term phenotypic consequences of early life painful procedures in farm animals is greatly lacking, despite obvious implications for welfare and performance. Improved understanding of how these procedures shape phenotypes will inform efforts to mitigate negative outcomes through reduction, replacement, and refinement of current practices.

Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long-term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments (n = 7-10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first 6 days of life with 0.2 mg/g body wt of respective treatments (24% solution; 1-4 μL/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 wk onto a control diet and fed until age 16 wk. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice (P < 0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor- 1 than adult water-treated female mice (P < 0.05); these effects were not observed in males. Lower liver S-adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared with water-treated female and male mice (P < 0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared with water-treated female mice (P < 0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism. [ABSTRACT FROM AUTHOR]

Introduction:  Wound dressing, a procedure that pediatric patients are commonly exposed to postoperatively, can cause strong physiological and pain behavioral responses despite being brief. This study evaluated the effects of using 24% sucrose plus a pacifier versus a pacifier alone to reduce the pain response from dressing wounds in neonates and infants.Materials and Methods:  Thirty-two neonates and infants who underwent surgery and required postoperative wound dressing were randomized to a pacifier group (n = 16) and a 24% sucrose plus pacifier group ("sucrose group"; n = 16). Demographic data, crying time, and pain behaviors were recorded using a video recorder. The pain behaviors were assessed independently using the neonatal infant pain scale (NIPS) by three assessors, who were expert in pediatric pain assessment and blinded to the subject allocations.Results:  Participants in the sucrose group were older than those in the pacifier group (6.19 ± 2.95 vs. 3.88 ± 3.2 months). While there were no differences in the NIPS scores of the two groups at 30, 120, and 240 seconds, the incidence of moderate-to-severe pain was lower in the sucrose group than the pacifier group at 120 seconds (37.5 vs. 50%). The crying time was lower in the sucrose group, but without statistical significance.Conclusion:  The 24% sucrose plus pacifier was not superior to the pacifier alone in decreasing pain behavioral responses. Dressing wound pain produced a high-intensity pain behavioral response. A pain management strategy should be developed to lessen the postoperative procedural pain in pediatric patients. [ABSTRACT FROM AUTHOR]

Early life adversity, including that which occurs in a medical setting, has been increasingly shown to have lasting consequences on both physical and mental health. In order to understand the lasting effects of early-life adversity, such as that might occur in the neonatal intensive care unit (NICU), several rodent models have been developed including maternal separation, neonatal handling, and repeated needle prick pain. However, in the clinical scenario, these stressors are often combined. Thus, the current study seeks to observe the lasting impacts of both neonatal pain and maternal separation in a rodent model. Rats were separated from their dam for 6 h per day during the first 7 days of life, during which they were subjected to repeated needle prick pain or handling. A separate group was left undisturbed. All rats were subsequently tested for threat processing using a 3-day Pavlovian fear conditioning model and for somatosensation using measures of mechanical and thermal thresholds. Results indicated that rats subjected to maternal separation and pain had enhanced fear conditioning in adolescence as well as displaying a modest age-independent tactile hypersensitivity compared to undisturbed controls. These data show that experiencing combined neonatal pain and maternal separation may create a latent vulnerability to subsequent stressors. [ABSTRACT FROM AUTHOR]

Exposure to stress at an early age programs the HPA axis which can lead to cognitive deficits in adults. However, it is not known whether these deficits emerge in adulthood or are expressed earlier in life. The aims of the study were to investigate (1) the immediate effects of early injury-induced stress in one-day-old (P1) and repeated stress on at P1 and P2 rat pups on plasma corticosterone levels; and (2) examine the subsequent long-term effects of this early stress on spatial learning and memory, and stress reactivity in early P26-34 and late P45-53 adolescent male and female rats. Intra-plantar injection of formalin induced prolonged and elevated levels of corticosterone in pups and impaired spatial learning and short- and long-term memory in late adolescent males and long-term memory in early adolescent females. There were sex differences in late adolescence in both learning and short-term memory. Performance on the long-term memory task was better than that on the short-term memory task for all early adolescent male and female control and stressed animals. Short-term memory was better in the late age control rats of both sexes and for formalin treated females as compared with the early age rats. These results are consistent with an impaired function of structures involved in memory (the hippocampus, amygdala, prefrontal cortex) after newborn pain. However, activation of the HPA axis by neonatal pain did not directly correlate with spatial learning and memory outcomes and the consequences of neonatal pain remain are likely multi-determined.

Intense research for more than three decades expelled the view that neonates do not experience pain. The aim of this survey was to investigate whether the Greek physicians involved in neonatal intensive care have changed their perceptions regarding neonatal pain, adapting their management practices to the knowledge that have emerged in the past 20-years. This study is a survey conducted at two time-points, 20 years apart. Anonymous questionnaires were distributed to 117 and 145 physicians working in neonatal intensive care units (NICUs) all over Greece in years 2000 and 2019, respectively. The response rate was 90.6 and 80.7% in 2000 and 2019, respectively. All respondents, at both time-points, believed that neonates experience pain, which has serious acute and long-term consequences, while the vast majority considered analgesia-sedation (A-S) during painful interventions as obligatory. Utilization of NICU protocols and pain assessment tools remained low although increased significantly between 2000 and 2019. The use of systemic A-S postoperatively was high at both time-points, while its implementation in infants subjected to prolonged pain, specifically mechanical ventilation, increased significantly by 2019. Systemic or local analgesia for acute procedural pain was used by lower proportions of physicians in 2019, except for the tracheal intubation. In contrast, the use of sweet solutions and non-pharmacological measures prior to or during bedside procedures significantly increased over time. Opioid administration significantly increased, while a shift from morphine to fentanyl was observed. International literature and perinatal–neonatal congresses were stated as the main sources of updating physicians' knowledge and improving management practice on neonatal pain prevention and treatment. In conclusion, Greek NICU-physicians' perceptions that neonates can experience pain with potentially serious acute and long-term consequences remained strong over the past 20 years. Although physicians' practices on neonatal pain management improved, they are still suboptimal, while significant differences exist among centers. Continuing education, globally accepted management protocols, and readily applied pain assessment tools would further improve the management of procedural pain and stress in neonates.

Exposure to stress at an early age programs the HPA axis which can lead to cognitive deficits in adults. However, it is not known whether these deficits emerge in adulthood or are expressed earlier in life. The aims of the study were to investigate (1) the immediate effects of early injury-induced stress in one-day-old (P1) and repeated stress on at P1 and P2 rat pups on plasma corticosterone levels; and (2) examine the subsequent long-term effects of this early stress on spatial learning and memory, and stress reactivity in early P26-34 and late P45-53 adolescent male and female rats. Intra-plantar injection of formalin induced prolonged and elevated levels of corticosterone in pups and impaired spatial learning and short- and long-term memory in late adolescent males and long-term memory in early adolescent females. There were sex differences in late adolescence in both learning and short-term memory. Performance on the long-term memory task was better than that on the short-term memory task for all early adolescent male and female control and stressed animals. Short-term memory was better in the late age control rats of both sexes and for formalin treated females as compared with the early age rats. These results are consistent with an impaired function of structures involved in memory (the hippocampus, amygdala, prefrontal cortex) after newborn pain. However, activation of the HPA axis by neonatal pain did not directly correlate with spatial learning and memory outcomes and the consequences of neonatal pain remain are likely multi-determined. [ABSTRACT FROM AUTHOR]

Introduction: Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants. Methods: A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 240/7 to 356/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB. Results: The overall mean TcB-TSB difference was −24.5 μmol/L (95% LOA −103.3 to 54.3), 1.6 μmol/L (95% LOA −73.4 to 76.5) before phototherapy, and −31.1 μmol/L (95% LOA −105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was −15.2 μmol/L (95% LOA −86.8 to 56.3) at the forehead and −24.4 μmol/L (95% LOA −112.9 to 64.0) at the sternum. The mean TcB-TSB difference was −31.4 μmol/L (95% LOA −95.3 to 32.4) among infants born 24–28 weeks, −25.5 μmol/L (95% LOA −102.7 to 51.8) at 29–32 weeks, and −15.9 μmol/L (95% LOA −107.4 to 75.6) at 33–35 weeks. Measures did not differ by maternal ethnicity. Conclusion: Among preterm infants, TcB may offer a noninvasive, immediate approach to screening for hyperbilirubinemia with more careful use in preterm infants born at <33 weeks' gestation, as TcB approaches treatment thresholds. Its underestimation of TSB after the initiation of phototherapy warrants the use of TSB for clinical decision-making after the initiation of phototherapy. [ABSTRACT FROM AUTHOR]

Giuseppe De Bernardo,1 Marina Riccitelli,2 Desiree Sordino,1 Maurizio Giordano,3 Sabrina Piccolo,1 Giuseppe Buonocore,2 Serafina Perrone2 1Department of Emergency, NICU, AORN Santobono-Pausilipon, Naples, Italy; 2Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; 3Faculty of Medicine, Federico II University, Naples, Italy Objective: To test the hypothesis that oral administration of 24% sucrose associated with ­nonnutritive sucking in healthy newborns receiving venipuncture beyond the first week of life controls pain and pain-related variation in heart rate (HR) and noninvasive oxygen saturation (SpO2).Methods: A total of 66 term newborns were enrolled between February and September 2017 in the Neonatology Department of AORN Santobono-Pausilipon, Naples. They were randomly assigned to receive oral 1 mL 24% sucrose (treated group [TG], n=33; gestational age 38.53±1.49 weeks; body weight 3,035±55 g; age 22.40±6.82 weeks) or oral 1 mL 10% glucose (control group [CG], n=33; gestational age 38.91±1.45 weeks; body weight 3,203±65 g; age 23.36±7.02 weeks) 1 minute before and during venipuncture. Evaluations were carried out between 8 and 9 am in all newborns. The Neonatal Infant Pain Scale (NIPS) was used to assess pain in newborns. Outcome measurements (HR, SpO2) were obtained before (T0), during (T1), and 1 minute after (T2) venipuncture using a Nellcor bedside SpO2 patient-monitoring system. NIPS scores were recorded throughout the procedure. Statistical analysis was performed using SPSS version 20.0. Changes in HR and SpO2 were assessed by mixed ANOVA for repeated measures. NIPS scores were evaluated by Mann–Whitney U test.Results: There were no statistically significant differences in HR or SpO2 between TG and CG at T0. HR was significantly lower in TG than CG at both T1 and T2 (P

Background: Accurate neonatal pain assessment (NPA) is the key to neonatal pain management, yet it is a challenging task for medical staff. This study aimed to analyze the clinical practicability of the artificial intelligence based NPA (AI-NPA) tool for real-world blood sampling. Method: We performed a prospective study to analyze the consistency of the NPA results given by a self-developed automated NPA system and nurses’ on-site NPAs (OS-NPAs) for 232 newborns during blood sampling in neonatal wards, where the neonatal infant pain scale (NIPS) was used for evaluation. Spearman correlation analysis and the degree of agreement of the pain score and pain grade derived by the NIPS were applied for statistical analysis. Results: Taking the OS-NPA results as the gold standard, the accuracies of the NIPS pain score and pain grade given by the automated NPA system were 88.79% and 95.25%, with kappa values of 0.92 and 0.90 (p < 0.001), respectively. Conclusion: The results of the automated NPA system for real-world neonatal blood sampling are highly consistent with the results of the OS-NPA. Considering the great advantages of automated NPA systems in repeatability, efficiency, and cost, it is worth popularizing the AI technique in NPA for precise and efficient neonatal pain management.

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life. Beginning on postnatal day, 24 male and female rats were subjected to a 4-day fear conditioning and sensory testing protocol. Some subjects received intra-amygdalar administration of either Vehicle, the CRF receptor 1 (CRF1) receptor antagonist Antalarmin, or the CRF receptor 2 (CRF2) receptor antagonist Astressin 2B prior to fear conditioning and somatosensory testing, while others had tissue collected following fear conditioning and CRF expression in the CeA and BLA was assessed using fluorescent in situ hybridization. CRF1 antagonism attenuated fear-induced hypersensitivity in neonatal pain and handled rats, while CRF2 antagonism produced a general antinociception. In addition, neonatal pain and handling produced a lateralized sex-dependent decrease in CRF expression, with males showing a diminished number of CRF-expressing cells in the right CeA and females showing a similar reduction in the number of CRF-expressing cells in the left BLA compared to undisturbed controls. These data show that the amygdalar CRF system is a likely target for alleviating dysfunction produced by early life trauma and that this system continues to play a major role in the lasting effects of such trauma into the juvenile stage of development.

This paper presents the first multimodal neonatal pain dataset that contains visual, vocal, and physiological responses following clinically required procedural and postoperative painful procedures. It was collected from 58 neonates (27-41 gestational age) during their hospitalization in the neonatal intensive care unit. The visual and vocal data were recorded using an inexpensive RGB camera while the physiological responses (vital signs and cortical activity) were recorded using portable bedside monitors. The recorded behavioral and physiological responses were scored by expert nurses using two validated pain scales to obtain the ground truth labels. In addition to behavioral and physiological responses, our dataset contains clinical information such as the neonate’s age, gender, weight, pharmacological and non-pharmacological interventions, and previous painful procedures. The presented multimodal dataset can be used to develop artificial intelligence systems that monitor, assess, and predict neonatal pain based on the analysis of behavioral and physiological responses. It can also be used to advance the understanding of neonatal pain, which can lead to the development of effective pain prevention and treatment.

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life. Beginning on postnatal day, 24 male and female rats were subjected to a 4-day fear conditioning and sensory testing protocol. Some subjects received intra-amygdalar administration of either Vehicle, the CRF receptor 1 (CRF1) receptor antagonist Antalarmin, or the CRF receptor 2 (CRF2) receptor antagonist Astressin 2B prior to fear conditioning and somatosensory testing, while others had tissue collected following fear conditioning and CRF expression in the CeA and BLA was assessed using fluorescent in situ hybridization. CRF1 antagonism attenuated fear-induced hypersensitivity in neonatal pain and handled rats, while CRF2 antagonism produced a general antinociception. In addition, neonatal pain and handling produced a lateralized sex-dependent decrease in CRF expression, with males showing a diminished number of CRF-expressing cells in the right CeA and females showing a similar reduction in the number of CRF-expressing cells in the left BLA compared to undisturbed controls. These data show that the amygdalar CRF system is a likely target for alleviating dysfunction produced by early life trauma and that this system continues to play a major role in the lasting effects of such trauma into the juvenile stage of development. [ABSTRACT FROM AUTHOR]

Purpose: The rising issue of opioid use during pregnancy poses an increased risk of fetal exposure to opioids in-utero and the development of neonatal abstinence syndrome (NAS). The cessation of exposure to opioids upon birth causes elevated levels of norepinephrine in the circulation enhancing sympathetic arousal. Skin conductance (SC) detects sympathetic-mediated sweating while the Neonatal Facial Coding System (NFCS) depicts facial expressions of stress and pain. We hypothesize that there will be a direct correlation between SC and NFCS scores, such that neonates with prenatal opioid exposure will have higher SC and facial responses to pain/stress as compared with healthy neonates without prenatal opioid exposure. Objective: This study evaluates the utility of SC and the NFCS in the objective assessment of early postnatal pain response in opioid-exposed and non-opioid exposed neonates. Methods: This prospective, single-center, pilot study enrolled opioid-exposed term neonates (>37 weeks) and healthy controls. Subjects were observed within 24–48 hours post-birth (and prior to opioid withdrawal) for pain at baseline, during, and post-heel lance/squeeze (HLS) with simultaneously measured SC and videotaped facial expressions. SC data included electro-dermal responses over time (EDR/second) and the average amplitude of responses (mean of peaks [MP]). Video data were scored using the NFCS by two trained coders with inter-rater agreement >85%. Results: SC and NFCS scores were significantly associated with both groups. The opioid-exposed neonates had significantly higher skin conductance indices, EDR/sec for the HLS phase, and MP for HLS and post phases as compared with controls (p <.05). Opioid-exposed neonates demonstrated higher NFCS at baseline (p =.003). Conclusions: Prenatal opioid exposure was associated with heightened sympathetic arousal during both pain and recovery phases and higher facial expressions of pain/distress at baseline only. A multimodal system of assessment may be useful in understanding the complexity and severity of opioid withdrawal associated with NAS. [ABSTRACT FROM AUTHOR]