Lower plasma melatonin levels in non-hypoxic premature newborns associated with neonatal pain.

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.

Repetitive neonatal procedural pain affects stress-induced plasma corticosterone increase in young adult females but not in male rats.

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.

ALPS-Neo pain and stress assessment scale for neonates-A measure for procedural pain.

AIM: The aim of this study was to investigate psychometric properties, reliability and validity, of Astrid Lindgren and Lund Children's Hospitals Pain and Stress Assessment Scale for Preterm and Sick Newborn Infants (ALPS-Neo), as a measure for procedural pain. METHODS: This observational, prospective study with a repeated measures design, explored inter-rater reliability by two raters assessing 21 neonates during non-pain and pain events. Construct validity was explored, that is, ability to discriminate between non-pain and pain, and criterion validity by correlating ALPS-Neo with Premature Infant Pain Profile-Revised (PIPP-R) and Skin Conductance Algesimeter (SCA) in 54 neonates without ventilator support and sedation undergoing routine heel-stick procedure in a tertiary neonatal intensive care unit. RESULTS: Mean gestational and assessment age of 54 infants was 33.8 weeks and 12.7 days respectively. Inter-rater reliability from baseline, skin wiping, heel-stick events for 21 infants demonstrated intraclass correlations with 95% confidence intervals (CI) of 0.49 (-0.27 to 0.79), 0.86 (0.65-0.94) and 0.73 (0.34-0.89) respectively. ALPS-Neo discriminated significantly between baseline, non-pain and heel-stick (mean differences from pain event -2.3 and -1.0 respectively) and correlated during heel-stick with PIPP-R (r = 0.56, 95% CI: 0.34-0.72), not with SCA. CONCLUSION: ALPS-Neo may be used as a measure for procedural pain.

Minor painful procedures in extremely preterm infants admitted to a tertiary neonatal intensive care unit: Opportunities to improve pain mitigation.

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.

Measurement of Cumulative Preterm Neonatal and Maternal Stressors During Neonatal Intensive Care Unit Admission.

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.

Comparison of the analgesic effect of inhaled lavender vs vanilla essential oil for neonatal frenotomy: a randomized clinical trial (NCT04867824).

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.

Effect of kangaroo mother care on pain during orogastric tube insertion in low-birthweight newborns: An open label, randomised trial.

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.

Quality Assessment of Neonatal Pain Scales Translated and Validated to Brazilian Portuguese: A Systematic Review of Psychometric Properties.

OBJECTIVES: 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. DESIGN: 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. DATA SOURCES: 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). REVIEW /ANALYSIS METHODS: 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. RESULTS: Three instruments reviewed were inadequate and one was doubtful. CONCLUSIONS: 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.

Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood.

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.

Maternal separation with neonatal pain influences later-life fear conditioning and somatosenation in male and female rats.

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.

Knowledge, attitudes and practices of neonatal professionals regarding pain management.

Pain management is an important issue which impacts the prognosis of neonates in neonatal intensive care units. Evidence has shown that professionals' knowledge and attitudes regarding pain management can impact the quality of their practice. The purpose of this study was to evaluate the knowledge, attitudes, and practices of neonatal professionals regarding neonatal pain management. A cross-sectional study was performed involving neonatal physicians and nurses, using a research questionnaire to investigate the knowledge and attitudes of professionals as well as to assess their practice of pain management. Research found an apparent discrepancy between the knowledge levels of neonatologists and nurses regarding pain assessment and management, with nurses displaying weaker professional knowledge and more negative attitudes toward pain management than did neonatologists. Additionally, research revealed a lack of knowledge and negative attitudes among participants regarding the provision of sufficient opioid analgesics to sick infants during invasive procedures and even for dying neonates. There is an urgent need for continuing education regarding neonatal pain management with the goal of empowering neonatal professionals; further research is needed into the question of how to translate education into more reliable practice.Conclusion: This research provides useful information regarding the knowledge, attitudes, and clinical practice of neonatal pain management among neonatologists and nurses and points out some differences in the knowledge levels of these two groups. What is Known: •Neonates can perceive and respond to pain stimuli by showing their biological signals similarly to children and adults. •Untreated or insufficient pain management for high-risk neonates has short-term. negative effects and may also induce long-term negative effects. What is New: •The level of knowledge, the attitudes, and the practices regarding neonatal pain in intensive care are different among neonatal professionals. •There is an urgent need to provide interdisciplinary continuing education to improve the knowledge of neonatal professionals and encourage them to more highly prioritize neonatal pain management.

Neonatal pain modulates in adolescent rats the antinociceptive effects of fluoxetine and buspirone administrated to their depressive dams during gestation.

Previously, we have shown that the administration of a selective serotonin reuptake inhibitor fluoxetine or a 5-HT1A receptor agonist buspirone to stressed rats during gestation causes in the offspring alleviation of formalin-induced pain, strengthened by prenatal stress. We have also found that neonatal inflammatory pain strengthens formalin-induced pain in prenatally unstressed rats in later life. In the present study, we investigated the effect of neonatal inflammatory pain on the time-course of the biphasic pain response in the formalin test in prenatally stressed adolescent rats of both sexes to evaluate whether neonatal pain affects the antinociceptive properties of these drugs administered to their depressed mothers during gestation. Our findings demonstrate that neonatal pain modulates in prenatally stressed rats the antinociceptive effect of fluoxetine and buspirone depending on the level of organization of pain response in the central nervous system, the phase of the time-course of the formalin-induced pain, and sex of the rat.

The clinical utility of the pain assessment tool in ventilated, sedated, and muscle-relaxed neonates.

BACKGROUND: The neonatal Pain Assessment Tool (PAT) is considered a reliable and valid tool for assessing neonatal pain. No research has been conducted on the clinical utility of the PAT when assessing pain in ventilated, sedated, and muscle-relaxed neonates. OBJECTIVE: The objective of the study was to determine the clinical utility of the PAT when assessing pain in ventilated, sedated, and muscle-relaxed neonates. METHODS: Neonatal nurses from the Royal Children's Hospital completed online surveys to assess the clinical utility of the PAT. Three focus groups were then conducted to further explore the variation of pain scores from the survey and clarify the challenges in interpreting the pain score. RESULTS: Nurses perceived the PAT clinically useful in neonates who were ventilated and minimally sedated. However, the PAT was not clinically useful in neonates who were ventilated and heavily sedated or muscle-relaxed. Further exploration via focus groups highlighted two themes related to the 'variation in the timing of the pain score' and the 'integration of critical thinking and judgement' used when assessing pain in neonates. CONCLUSIONS: The clinical utility of the PAT is acceptable for minimally sedated neonates; however, it decreases the more sedated a neonate becomes, and the PAT's usefulness is extremely poor in the muscle-relaxed neonate. A better understanding of the timing and interpretation of the pain score in relation to the neonate's clinical status may enable improved decision-making and pain management. The PAT requires further validity, reliability, and clinical utility research, particularly in critically ill and muscle-relaxed neonates.

Evidence-based clinical guidelines on analgesia and sedation in newborn infants undergoing assisted ventilation and endotracheal intubation.

AIM: This review informed pain control guidelines for clinicians performing mechanical ventilation, nasal continuous positive airway pressure and endotracheal intubation on term and preterm newborn infants. METHODS: We reviewed literature published between 1986 and June 2017 on analgesia and sedation during assisted ventilation and before endotracheal intubation in newborn infants admitted to neonatal intensive care units. The subsequent guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Our review produced five strong standard of care recommendations. One, reduce neonatal stress and use nonpharmacological analgesia during invasive ventilation. Two, favour intermittent boluses of opioids, administered after pain scores and before invasive procedures, during short expected periods of mechanical ventilation, mainly in preterm infants affected by respiratory distress syndrome. Three, do not use morphine infusion in preterm infants under 27 gestational weeks. Four, always use algometric scores to titrate analgesic drugs doses. Five, use premedication before endotracheal intubation for a more rapid, less painful, less traumatic and safer manoeuvre. We also developed 30 conditional recommendations on therapeutic options. CONCLUSION: Our review produced 35 recommendations on standard care and therapeutic options relating to the analgesia and sedation of newborn infants during ventilation and before endotracheal intubation.

Neonatal pain and stress disrupts later-life pavlovian fear conditioning and sensory function in rats: Evidence for a two-hit model.

Early life trauma has been linked to increased risks for anxiety, depression, and chronic pain. We used rodent models of acute and inflammatory neonatal pain to explore effects on fear conditioning and somatosensory function. Hindpaw needle pricks or handling on postnatal days (PNDs) 1-7 caused lasting impacts on affective and somatosensory function when assessed at later ages, PNDs 24 (postweaning), 45 (adolescence), or 66 (adulthood). First, auditory, but not contextual, freezing was mildly disrupted regardless of age. Second, a profound postfear conditioning tactile hypersensitivity was observed in neonatally stressed, postweaning rats. In the absence of fear conditioning, the mechanical hypersensitivity was not observed, consistent with a two-hit model of psychopathology. Injections of 2% α-carrageenan did not have the same lasting impact but was slightly protective against observed effects of neonatal vehicle injections. Basal and elicited corticosterone levels postweaning were not altered by neonatal pain or handling. These data demonstrate that neonatal adversity can have lasting impacts on affective and somatosensory function that differs regardless of age.

Evaluation of three pain assessment scales used for ventilated neonates.

AIMS AND OBJECTIVES: To compare and evaluate the reliability, validity, feasibility, clinical utility, and nurses' preference of the Premature Infant Pain Profile-Revised, the Neonatal Pain, Agitation, and Sedation Scale, and the Neonatal Infant Acute Pain Assessment Scale used for procedural pain in ventilated neonates. BACKGROUND: Procedural pain is a common phenomenon but is undermanaged and underassessed in hospitalised neonates. Information for clinician selecting pain measurements to improve neonatal care and outcomes is still limited. DESIGN: A prospective observational study was used. METHODS: A total of 1,080 pain assessments were made at 90 neonates by two nurses independently, using three scales viewing three phases of videotaped painful (arterial blood sampling) and nonpainful procedures (diaper change). Internal consistency, inter-rater reliability, discriminant validity, concurrent validity and convergent validity of scales were analysed. Feasibility, clinical utility and nurses' preference of scales were also investigated. RESULTS: All three scales showed excellent inter-rater coefficients (from 0.991-0.992) and good internal consistency (0.733 for the Premature Infant Pain Profile-Revised, 0.837 for the Neonatal Pain, Agitation, and Sedation Scale and 0.836 for the Neonatal Infant Acute Pain Assessment Scale, respectively). Scores of painful and nonpainful procedures on the three scales changed significantly across the phases. There was a strong correlation between the three scales with adequate limits of agreement. The mean scores of the Neonatal Pain, Agitation, and Sedation Scale for feasibility and utility were significantly higher than those of the Neonatal Infant Acute Pain Assessment Scale, but not significantly higher than those of the Premature Infant Pain Profile-Revised. The Neonatal Pain, Agitation, and Sedation Scale was mostly preferred by 55.9% of the nurses, followed by the Neonatal Infant Acute Pain Assessment Scale (23.5%) and the Premature Infant Pain Profile-Revised (20.6%). CONCLUSIONS: The three scales are all reliable and valid, but the Neonatal Pain, Agitation, and Sedation Scale and the Neonatal Infant Acute Pain Assessment Scale perform better in reliability. The Neonatal Pain, Agitation, and Sedation Scale appears to be a better choice for frontier nurses to assess procedural pain in ventilated neonates based on its good feasibility, utility and nurses' preference. RELEVANCE TO CLINICAL PRACTICE: Choosing a valid, reliable, feasible and practical measurement is the key step for better management of procedural pain for ventilated newborns. Using the right and suitable tool is helpful to accurately identify pain, ultimately improve the neonatal care and outcomes.

Preterm infants exhibited less pain during a heel stick when they were played the same music their mothers listened to during pregnancy.

AIM: Playing music during painful procedures has shown inconsistent benefits for preterm infants. This study observed preterm infants during a heel stick procedure to assess whether listening to the music their mothers listened to during pregnancy had any impact on their pain and physiological and behavioural parameters. METHODS: We randomly exposed 42 preterm infants, with a mean gestational age of 31.8 ± 2.79 weeks, to the music their mothers listened to during pregnancy, recorded lullabies and no music, before, during and after a heel stick. Pain responses were measured using the Neonatal Pain, Agitation and Sedation Scale (N-PASS), and physiological and behavioural responses were recorded by a nurse blinded to the intervention. RESULTS: N-PASS pain scores were lowest during mothers' music, with a mean of 1.40 (±1.28), compared to 2.33 (±1.64) for no music and 1.62 (±2.27) for the lullabies [F(3/121) = 4.86, p = 0.009]. Physiological parameters were not significantly different between the conditions. During the mothers' music, infants spent more time in a quiet alert state, with a significant decrease in their respiratory rates. CONCLUSION: The music mothers listened to during pregnancy was more beneficial for preterm infants, as it decreased pain and improved behavioural states during a heel stick.

Does Pain in the Neonatal Period Influence Motor and Sensory Functions in a Similar Way for Males and Females During Post-Natal Development in Rats?

OBJECTIVE : Early pain experiences can lead to disruption in the long-term responses to pain and in abnormal development and behavior in rodents. We evaluated the sensory and motor development of Wistar rats after exposure to painful stimulation (repetitive needle prickling) immediately after birth. METHODS : Male and female rats were followed up to 6 months of life, and sensory and motor functions were investigated by testing paw withdrawal with von Frey filaments, calibrated forceps (CF), and grip strength (GS) tests. RESULTS : Body weight increased with age and tended to be smaller in pain groups compared with their controls of the same sex. GS values also increased with age in controls but were stable and even decreased in pain groups from 120 up to 180 days. The von Frey filaments test showed higher values on the nonstimulated paws in male and female pain groups, with no differences between sides on the controls. The CF test showed smaller values on the stimulated paws in the pain group, with no differences between sides on the controls. CONCLUSIONS : Pain in the neonatal period influences sensory and motor functions negatively during development in male and female rats, even long term after the painful stimulus is ceased. The neonatal injury-induced hypersensitivity is persistent, and male and female rats respond similarly to the stimulus.

The implementation of systematic pain and sedation management has no impact on outcome in extremely preterm infants.

AIM: This study compared the short-term and neurodevelopmental outcomes of extremely preterm infants before and after the implementation of a protocol to manage neonatal pain and sedation. METHODS: Our study cohort comprised 140 extremely preterm infants from two neonatal intensive care units. We retrospectively analysed opiate exposure, time on mechanical ventilation, inotropic support, nutritional aspects and growth 12 months before (controls) vs 12 months after (intervention) the implementation of the Vienna Protocol for Neonatal Pain and Sedation. Infants were evaluated at the corrected age of 12 months using the Bayley Scales of Infant Development - Second Edition. RESULTS: After the protocol was implemented, the cumulative opiate dose increased from a baseline of 15 mg/kg ± 41 to 89 mg/kg ± 228 morphine equivalents. Time on mechanical ventilation, inotropic support, length of parenteral nutrition, growth, length of stay and in-hospital morbidity were similar before and after the implementation, with no differences between the groups in mental, motor and behavioural development at the one-year follow-up. However, opiate exposure was a possible risk factor for lower behaviour rating scores (estimate = -0.04; p = 0.006). [Correction added on 23 February 2016, after online publication: In the preceding sentences, the cumulative opiate dose as well as the estimate value for the behavioral rating scale were previously incorrect and have been amended in this current version.] CONCLUSION: Implementing a neonatal pain and sedation protocol increased opiate exposure, but had no effect on the in-hospital and neurodevelopmental outcomes of extremely preterm infants.

The validity and reliability of the EValuation of INtervention Scale: preliminary report.

AIM: Pain management is a priority for infants receiving neonatal care as they undergo many necessary painful and stressful interventions, which are associated with negative short- or long-term consequences. This study aims to validate the content, and test the reliability, of the EValuation of INtervention Scale (EVIN), which is designed to evaluate the use of widely recommended nonpharmacological strategies to reduce neonatal pain and stress during procedures. METHODS: The content of the EVIN was validated with multidisciplinary participation (N = 80), and consistency was established via observations on preterm infants (N = 12, at 31-34 weeks' gestation) during interventions in a neonatal unit. A revised scale was tested for inter-rater reliability with observations of invasive (blood sampling, N = 16) and noninvasive (nappy change, N = 18) interventions. The intraclass correlation coefficient (ICC) was used to determine inter-rater reliability. SPSS (PASW Statistics) version 18 was used for analysis. RESULTS: Very good intraclass correlation coefficients (>0.8) for both invasive (0.962) and noninvasive procedures (0.970) were achieved. CONCLUSION: These results indicate that the EVIN is suitable for the evaluation of nonpharmacological support during painful or stressful interventions.