Heel Lance Research Articles

Statistical analysis plan for the Petal trial: the effects of parental touch on relieving acute procedural pain in neonates

Background Infants undergo multiple clinically-required painful procedures during their time in hospital, and there is an increasing desire from both parents and clinical staff to have parents directly involved in their newborn’s pain relief. To avoid biases due to selective analysis and reporting, a clinical trial’s statistical analysis plan (SAP) should be finalised and registered prior to dataset lock and unblinding. Here, we outline the SAP for the Petal trial, which was registered on the ISRCTN registry prior to dataset lock and unblinding. Methods The Petal trial is a multicentre, individually randomised, parallel-group interventional superiority trial. The study involves in-patient neonates born at or after 35+0 weeks gestation with a postnatal age of ≤7 days, in two hospital research sites (John Radcliffe Hospital, Oxford, UK; Royal Devon and Exeter Hospital, Exeter, UK). The primary objective is to investigate the potential efficacy of a non-pharmacological parent-led stroking intervention on reducing the magnitude of neonates’ noxious stimulus-evoked brain activity. The primary outcome is the neonate’s brain activity recorded using electroencephalography (EEG) in response to a heel lance blood sampling procedure. Secondary outcomes include neonatal clinical pain scores and tachycardia, and parental anxiety. The study hypothesis is neonates’ pain responses and parents’ anxiety scores are lower in the intervention group. Randomisation will be via a minimisation algorithm to maintain balance in five prognostic factors. Conclusions Paediatric pain trials have been highlighted by regulatory bodies as an important and challenging topic, with interest increasing in brain imaging outcomes. The Petal trial, to which this SAP relates, is part of a larger effort of establishing a brain-based EEG outcome measure of infant pain for use in clinical trials. This SAP is thus likely to be of interest to those in academia, pharmaceutical companies, and regulatory bodies. Trial registration ClinicalTrials.gov: NCT04901611, 25/05/2021; ISRCTN: ISRCTN14135962, 23/08/2021).

Effect of kangaroo mother care and white noise on physiological-stress parameters in heel lancing: randomized controlled study

BackgroundNewborns are exposed to varying degrees of stressful interventions due to procedures such as heel lancing used in routine metabolic screenings. It is an examination of the effects of white noise and kangaroo care on some physiological parameters and stress markers (cortisol and glucose-regulated protein 78-GRP78) in heel lancing in newborns.MethodsRandomized controlled study was conducted at a gynecology service of a hospital between January and September 2023. 90 babies were divided into three groups: 30 babies in the Kangaroo Care Group (KCG), 30 babies in the White Music Group (WMG), and 30 babies in the Control Group (CG). All babies were randomly divided into groups. Stress parameters were measured by saliva collection method and physiological parameters by saturation device.ResultsA statistically significant difference was determined between the total crying time, pulse and saturation values ​​according to the groups (p < 0.001; p = 0.001). A statistically significant difference was determined between the mean values ​​of cortisol and GRP78 measurements according to group and time interaction (p < 0.001). KCG was more effective in reducing total crying time and stabilizing pulse, saturation, salivary cortisol, GRP-78 values compared to WNG and CG.ConclusionIt was concluded that white noise and kangaroo care help reduce newborns’ stress in the case of heel lancing.Practical implicationsThe practice of kangaroo care and the use of white noise methods may assist healthcare professionals as supportive methods in stress management during invasive procedures.Trial RegistrationNCT06278441, registered on 19/02/2024.

Neonatal paw pricking alters adolescent behavior in a sex-dependent manner and sucrose partially remediates the effects

Neonatal exposure to noxious stimuli such as repeated heel lances can cause behavior changes. In the NICU sucrose given prior to procedures attenuates the immediate behavioral response to noxious stimuli but may not ameliorate the long-term consequences, and treatment with 24 % sucrose can brain structure and behavior in adult rodents. We used a rat model to determine whether paw pricks during the neonatal period alter social interaction and/or paw withdrawal thresholds (PWT) in adolescence, and if 7 % sucrose mitigates these effects. One male and one female pup per litter was assigned to each of six experimental groups (no paw prick (control), 1 paw prick (1PP), or 2PP, ± sucrose). Hind paws were pricked once or twice each day between postnatal day (P)3 and P10. Social behavior and PWT were tested in adolescence using the modified social interaction test and von Frey filaments, respectively. Social behavior was altered in the 2PP group; total time interacting was lower in 2PP rats, primarily due to less time sniffing a play partner. Sucrose did not mitigate effects of paw prick but trended to alter social behaviors in males; it decreased time in contact but increased social motivation (movement toward a play partner). PWTs were higher in 2PP animals, this was not altered by sucrose. Thus, rat pups exposed to paw pricks in the neonatal period have some altered behaviors in adolescence. The nature of the behavioral changes is sex-dependent, but sucrose did not mitigate these changes.

Establishing a standardised approach for the measurement of neonatal noxious-evoked brain activity in response to an acute somatic nociceptive heel lance stimulus

BackgroundElectroencephalography (EEG) can be used in neonates to measure brain activity changes that are evoked by noxious events, such as clinically required immunisations, cannulation and heel lancing for blood tests. EEG provides an alternative approach to infer pain experience in infants compared with more commonly used behavioural and physiological pain assessments. Establishing the generalisability and construct validity of these measures will help corroborate the use of brain-derived outcomes to evaluate the efficacy of new or existing pharmacological and non-pharmacological methods to treat neonatal pain. This study aimed to test whether a measure of noxious-evoked EEG activity called the noxious neurodynamic response function (n-NRF), that was originally derived in a sample of term-aged infants at the Oxford John Radcliffe Hospital, UK, in 2017, can reliably distinguish noxious from non-noxious events in two independent datasets collected at University College London Hospital and at Royal Devon & Exeter Hospital. We aimed to reproduce three published results that use this measure to quantify noxious-evoked changes in brain activity. We used the n-NRF to quantify noxious-evoked brain activity to test (i) whether significantly larger noxious-evoked activity is recorded in response to a clinical heel lance compared to a non-noxious control heel lance procedure; (ii) whether the magnitude of the activity evoked by a noxious heel lance is equivalent in independent cohorts of infants; and (iii) whether the magnitude of the noxious-evoked brain activity increases with postmenstrual age (PMA) in premature infants up to 37 weeks PMA. Positive replication of these studies will build confidence in the use of the n-NRF as a valid and reliable pain-related outcome which could be used to evaluate analgesic efficacy in neonates. The protocol for this study was published following peer review (https://doi.org/10.17605/OSF.IO/ZY9MS). ResultsThe n-NRF magnitude to a noxious heel lance stimulus was significantly greater than to a non-noxious control heel lance stimulus in both the UCL dataset (n = 60; mean difference .88; 95% confidence interval (CI) .64–1.13; p < .0001) and the Exeter dataset (n = 31; mean difference .31; 95% CI .02–.61; p = .02). The mean magnitude and 90% bootstrap confidence interval of the n-NRF evoked by the heel lance did not meet our pre-defined equivalence bounds of 1.0 ± .2 in either the UCL dataset (n = 72; mean magnitude 1.33; 90% bootstrapped CI 1.18–1.52) or the Exeter dataset (n = 35; mean magnitude .92, 90% bootstrapped CI .74–1.22). The magnitude of the n-NRF to the noxious stimulus was significantly positively correlated with PMA in infants up to 37 weeks PMA (n = 65; one-sided Pearson's R, adjusted for site: .24; 95% CI .06–1.00; p = .03). ConclusionsWe have reproduced in independent datasets the findings that the n-NRF response to a noxious stimulus is significantly greater than to a non-noxious stimulus, and that the noxious-evoked EEG response increases with PMA. The pre-defined equivalence bounds for the mean magnitude of the EEG response were not met, though this might be due to either inter-site differences such as the lack of calibration of devices between sites (a true negative) or underpowering (a false negative). This reproducibility study provides robust evidence that supports the use of the n-NRF as an objective outcome for clinical trials assessing acute nociception in neonates. Use of the n-NRF in this way has the potential to transform the way analgesic efficacy studies are performed.

Effect of oral glucose administration on pain intensity among preterm neonates during heel lancing

Effect of oral glucose administration on pain intensity among preterm neonates during heel lancing

Performance Evaluation of a Supervised Machine Learning Pain Classification Model Developed by Neonatal Nurses.

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. To develop and validate a machine learning (ML) model to classify pain. 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. 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. 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.

Effects of automatic heel lancet on invasiveness in neonates: A systematic review and meta-analysis.

We conducted a meta-analysis comparing the invasiveness of automatic lancet devices, which can collect adequate amount of blood at shallow puncture depths, with conventional manual lance devices (lancet or needle) to statistically identify less invasive instruments for neonatal heel lance. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and Ichushi databases for studies comparing the invasiveness between automatic lancet and manual lancet or needle in term and preterm neonates in neonatal intensive care unit. This review included 9 out of 449 searched articles, with 673 neonates. Automatic lancet had significantly lower pain scores (standardised mean difference: -2.0, 95% confidence interval: -3.3 to -0.7), heart rate (mean difference: -8.0, 95% confidence interval: -13.8 to -2.1), cry duration (mean difference: -21.5, 95% confidence interval: -32.5 to -10.4), number of punctures (mean difference: -0.6, 95% confidence interval: -1.1 to -0.2), and duration of procedures (mean difference: -37.7, 95% confidence interval: -75.2 to -0.2) than manual lancet or needle. Furthermore, peripheral oxygen saturation was significantly higher in automatic lancet than in manual lancet or needle (mean difference: 4.5, 95% confidence interval: 0.5-8.5). Automatic heel lancet devices were less invasive than manual heel lance devices (lancet or needle).

Impact of Kangaroo Mother Care on Heart Rate Variability and Pain Score with Heel Lance Pain in Preterm Neonates: A Cross-over Randomized Controlled Trial

Introduction: To evaluate the effect of kangaroo care on response to pain due to heel lance in preterm infants using premature infant pain profile (PIPP). Design: Randomized cross-over design. Methods: Stable preterm neonates ( n = 70) who had completed 28–36 weeks of gestational age received either kangaroo mother care or were kept under control (bassinet) conditions for 30 minutes prior to a heel lance. The neonates were observed, and responses were scored as per PIPP. They were then crossed over to the other condition and scored similarly. The PIPP scores in the two study arms were then compared using appropriate statistical tools. Results: A total of 342 neonates were admitted during the study period, of which 95 were assessed for eligibility, and finally, 70 were included and randomized to be in one of the two arms. The facial actions differed in the two groups; the brow bulge and eye squeeze scores were significantly better at each observation in the KMC group. The nasolabial furrow score was significantly better at 60 and 90 seconds. The baseline PIPP scores were similar. In the KMC group, the scores were significantly lower at 30, 60, and 90 seconds post–heel lance. Conclusions: Kangaroo mother care is an effective way of reducing the physiological and behavioral effects of pain in preterm neonates.

Effect of parental touch on relieving acute procedural pain in neonates and parental anxiety (Petal): a multicentre, randomised controlled trial in the UK

Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief. Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611). Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study. Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management. Wellcome Trust and Bliss.

The effect of the simulated intrauterine sound on behavioral and physiological indices of pain during capillary blood sampling for screening preterm infants: a randomized clinical trial study

IntroductionDue to medical procedures, preterm infants are at high risk for side effects of pain. In this regard, heel lancing for capillary blood sampling is a common painful procedure. The present study was conducted to assess the effectiveness of a simulated intrauterine sound on behavioral and physiological indices of pain due to heel-prick blood sampling in preterm infants.MethodsA double‑blind randomized clinical trial (RCT) was conducted. The data were collected from September 23 to December 22, 2019. We measured the effect of a simulated intrauterine sound on changes in the behavioral and physiological parameters of pain (heart rate, SPO2) caused by heel lance that was measured 5 min before the intervention, during the sampling, and 5 min after the procedure. We measured behavioral pain by video recording the infants’ faces and then the scoring neonatal infant pain scale (NIPS). Heart rate and SPO2 were measured using a pulse oximeter device. The data were analyzed using analysis of variance (ANOVA) and independent t‑test in SPSS software version 20.0.ResultsEighty infants were randomized (40 in each group). Mean scores NIPS during and after intervention were in the intervention group (3.55 ± 0.84, 95% CI: 3.30–3.80(, and (1.15 ± 0.84, 95%: 0.95–1.35) and in the control group (5.57 ± 0.95, 95% CI:5.30–5.85) and (3.00 ± 0.98) respectively. There were significant differences in scores of NIPS between the two study groups during (p < 0.001) and five min after heel lancing (p < 0.001). Mean scores of heart rate in the three phases of before, during, and five min after the intervention were respectively in the intervention group (127.57 ± 4.45, 95% CI:126.27-128.99), (131.07 ± 6.54, 95% CI:129.20-133.22), (128.45 ± 5.15, 95% CI:127.02-130.07) and in the control group (128.67 ± 4.57, 95% CI:127.32-130.07), (136.07 ± 7.24, 95% CI:133.90-138.37), and (132.42 ± 6.47, 95% CI:130.37-134.49). There were significant differences in heart rate between the intervention and the control group during (p = 0.002) and five min after the heel lance (p = 0.003). Mean scores of SPO2 in the three phases of baseline, during, and five min after the intervention were respectively in the intervention group (96.72 ± 0.93, 95% CI:96.42-97.00), (91.47 ± 1.46, 95% CI:91.05–91.92), (94.17 ± 1.03, 95% CI:93.22-94.00) and in the control group (96.6 ± 0.84, 95% CI:96.35–96.85), (91.5 ± 1.24, 95% CI:91.12–91.87), and (93.60 ± 1.27, 95% CI:93.85–94.50).ConclusionThis study showed that the simulated intrauterine sound reduces the behavioral pain and heart rate in the intervention group during and after heel lance. These results suggest using the method during the painful heel lancing to reduce pain parameters in preterm infants.

Analgesic Effect of Low-Level Laser Therapy before Heel Lance for Pain Management in Healthy Term Neonates: A Randomized Controlled Trial.

Currently, the prevention, assessment, and management of procedural pain in neonates continues to challenge clinicians and researchers. Objective. To investigate the analgesic effect of low-level laser therapy (LLLT) during heel lance compared to breast milk (BM) feeding in healthy term neonates. In this randomized controlled trial, healthy term neonates who underwent heel lance were randomly assigned to an LLLT or a BM group. The LLLT group received laser therapy to the heel lance site for 20 s before heel lance. The BM group received 5 mL expressed BM via a syringe before heel lance. The primary outcomes were behavioral responses. The secondary outcomes were physiological responses and levels of salivary cortisol and α-amylase. A total of 125 neonates were included, of whom 55 in the LLLT group and 59 in the BM group completed the study. There were no significant differences in latency to first cry and cry duration between the two groups. The squeeze time was significantly shorter in the LLLT group than in the BM group (p = 0.047). There were no significant differences in pain scores, heart rate, respiratory rate, oxygen saturation, and blood pressure before and after heel lance between the two groups. There were no significant differences in salivary cortisol and α-amylase levels in the LLLT group before and after heel lance; however, the differences were significant in the BM group. These findings suggest that the analgesic effect of LLLT is similar to that of BM during heel lance in healthy term neonates. LLLT has potential as an analgesic treatment.

Experience of early-life pain in premature infants is associated with atypical cerebellar development and later neurodevelopmental deficits

BackgroundInfants born very and extremely premature (V/EPT) are at a significantly elevated risk for neurodevelopmental disorders and delays even in the absence of structural brain injuries. These risks may be due to earlier-than-typical exposure to the extrauterine environment, and its bright lights, loud noises, and exposures to painful procedures. Given the relative underdeveloped pain modulatory responses in these infants, frequent pain exposures may confer risk for later deficits.MethodsResting-state fMRI scans were collected at term equivalent age from 148 (45% male) infants born V/EPT and 99 infants (56% male) born at term age. Functional connectivity analyses were performed between functional regions correlating connectivity to the number of painful skin break procedures in the NICU, including heel lances, venipunctures, and IV placements. Subsequently, preterm infants returned at 18 months, for neurodevelopmental follow-up and completed assessments for autism risk and general neurodevelopment.ResultsWe observed that V/EPT infants exhibit pronounced hyperconnectivity within the cerebellum and between the cerebellum and both limbic and paralimbic regions correlating with the number of skin break procedures. Moreover, skin breaks were strongly associated with autism risk, motor, and language scores at 18 months. Subsample analyses revealed that the same cerebellar connections strongly correlating with breaks at term age were associated with language dysfunction at 18 months.ConclusionsThese results have significant implications for the clinical care of preterm infants undergoing painful exposures during routine NICU care, which typically occurs without anesthesia. Repeated pain exposures appear to have an increasingly detrimental effect on brain development during a critical period, and effects continue to be seen even 18 months later.

Statistical analysis plan for the Petal trial: the effects of parental touch on relieving acute procedural pain in neonates

Background: Infants undergo multiple clinically-required painful procedures during their time in hospital, and there is an increasing desire from both parents and clinical staff to have parents directly involved in their newborn’s pain relief. The Petal trial is a multicentre randomised controlled trial to investigate the effect of parental touch prior to a clinically-required heel lance on neonatal pain responses and parental anxiety. To avoid biases due to selective analysis and reporting, a clinical trial’s statistical analysis plan (SAP) should be finalised and registered prior to dataset lock and unblinding. Here, we outline the SAP for the Petal trial, which was registered on the ISRCTN registry prior to dataset lock and unblinding. The SAP is written in line with best practice guidelines to provide sufficient detail for reproducibility. Methods: The primary outcome is the neonate’s brain activity recorded using electroencephalography (EEG) in response to a heel lance blood sampling procedure. In this superiority trial, the primary objective is to investigate the potential efficacy of a parent-led non-pharmacological analgesic intervention on reducing the magnitude of neonates’ noxious stimulus-evoked brain activity. Secondary outcomes include neonatal clinical pain scores and tachycardia, and parental anxiety. Conclusions: Paediatric pain trials have been highlighted by regulatory bodies as an important and challenging topic, with interest increasing in brain imaging outcomes. The Petal trial, to which this SAP relates, is part of a larger effort of establishing a brain-based EEG outcome measure of infant pain for use in clinical trials. This SAP is thus likely to be of interest to those in academia, pharmaceutical companies, and regulatory bodies. We hope this SAP will help establish a foundation for the use of brain imaging outcomes in neonatal pain clinical trials, on which best practices can be built. Trial registration: ClinicalTrials.gov: NCT04901611, 25/05/2021; ISRCTN: ISRCTN14135962, 23/08/2021).

Impact of low-level prenatal alcohol exposure and maternal stress on autonomic regulation.

Prenatal alcohol exposure (PAE) impacts the neurodevelopment of the fetus, including the infant's ability to self-regulate. Heart rate variability (HRV), that is, the beat-to-beat variability in heart rate, is a non-invasive measurement that can indicate autonomic nervous system (ANS) function/dysfunction. The study consisted of a subset of our ENRICH-2 cohort: 80 participants (32 PAE and 48 Controls) who had completed three visits during pregnancy. The participants completed a comprehensive assessment of PAE and other substances throughout pregnancy and assessments for stress, anxiety, and depression in the third trimester. At 24 h of age, infant HRV was assessed in the hospital during the clinically indicated heel lance; 3- to 5-min HRV epochs were obtained during baseline, heel lancing, and recovery episodes. Parameters of HRV differed in infants with PAE compared to Controls during the recovery phase of the heel lance (respiratory sinus arrhythmia (RSA) and high-frequency (HF), p < 0.05). Increased maternal stress was also strongly associated with abnormalities in RSA, HF, and low-frequency / high-frequency (LF/HF, p's < 0.05). Alterations in ANS regulation associated with PAE and maternal stress may reflect abnormal development of the hypothalamic-pituitary-adrenal axis and have long term implications for infant responsiveness and self-regulation. Previous studies have focused on effects of moderate to heavy prenatal alcohol exposure (PAE) on autonomic dysregulation, but little is known about the effects of lower levels of PAE on infant self-regulation and heart rate variability (HRV). Prenatal stress is another risk factor for autonomic dysregulation. Mild PAE impacts infant self-regulation, which can be assessed using HRV. However, the effect of prenatal stress is stronger than that of mild PAE or other mental health variables on autonomic dysregulation.

A longitudinal observational study on the epidemiology of painful procedures and sucrose administration in hospitalized preterm neonates.

Although sucrose is widely administered to hospitalized infants for single painful procedures, total sucrose volume during the entire neonatal intensive care unit (NICU) stay and associated adverse events are unknown. In a longitudinal observation study, we aimed to quantify and contextualize sucrose administration during the NICU stay. Specifically, we investigated the frequency, nature, and severity of painful procedures; proportion of procedures where neonates received sucrose; total volume of sucrose administered for painful procedures; and incidence and type of adverse events. Neonates <32 weeks gestational age at birth and <10 days of life were recruited from four Canadian tertiary NICUs. Daily chart reviews of documented painful procedures, sucrose administration, and any associated adverse events were undertaken. One hundred sixty-eight neonates underwent a total of 9093 skin-breaking procedures (mean 54.1 [±65.2] procedures/neonate or 1.1 [±0.9] procedures/day/neonate) during an average NICU stay of 45.9 (±31.4) days. Pain severity was recorded for 5399/9093 (59.4%) of the painful procedures; the majority (5051 [93.5%]) were heel lances of moderate pain intensity. Sucrose was administered for 7839/9093 (86.2%) of painful procedures. The total average sucrose volume was 5.5 (±5.4) mL/neonate or 0.11 (±0.08) mL/neonate/day. Infants experienced an average of 7.9 (±12.7) minor adverse events associated with pain and/or sucrose administration that resolved without intervention. The total number of painful procedures, sucrose volume, and incidence of adverse events throughout the NICU stay were described addressing an important knowledge gap in neonatal pain. These data provide a baseline for examining the association between total sucrose volume during NICU stay and research on longer-term behavioral and neurodevelopmental outcomes.

The PiNe box: Development and validation of an electronic device to time-lock multimodal responses to sensory stimuli in hospitalised infants.

Recording multimodal responses to sensory stimuli in infants provides an integrative approach to investigate the developing nervous system. Accurate time-locking across modalities is essential to ensure that responses are interpreted correctly, and could also improve clinical care, for example, by facilitating automatic and objective multimodal pain assessment. Here we develop and assess a system to time-lock stimuli (including clinically-required heel lances and experimental visual, auditory and tactile stimuli) to electrophysiological research recordings and data recorded directly from a hospitalised infant's vital signs monitor. The electronic device presented here (that we have called 'the PiNe box') integrates a previously developed system to time-lock stimuli to electrophysiological recordings and can simultaneously time-lock the stimuli to recordings from hospital vital signs monitors with an average precision of 105 ms (standard deviation: 19 ms), which is sufficient for the analysis of changes in vital signs. Our method permits reliable and precise synchronisation of data recordings from equipment with legacy ports such as TTL (transistor-transistor logic) and RS-232, and patient-connected networkable devices, is easy to implement, flexible and inexpensive. Unlike current all-in-one systems, it enables existing hospital equipment to be easily used and could be used for patients of any age. We demonstrate the utility of the system in infants using visual and noxious (clinically-required heel lance) stimuli as representative examples.

Clotted blood samples in the neonatal intensive care unit: A retrospective, observational study to evaluate interventions to reduce blood sample clotting.

Blood draws for laboratory investigations are essential for patient management in neonatal intensive care units (NICU). When blood samples clot before analysis, they are rejected, which delays treatment decisions and necessitates repeated sampling. To decrease the incidence of rejected blood samples taken for laboratory investigation as a result of clotted sample. This retrospective observational study used routine data on blood draws from preterm infants collected between January 2017 and June 2019 in a 112-cot NICU in Qatar. Quality improvement interventions to reduce the rate of clotted blood samples included: awareness raising and safe sampling workshops with NICU staff, involvement of the neonatal vascular access team, development of a complete blood count (CBC) sample collection pathway, review of sample collection equipment, introducing the Tenderfoot® heel lance, establishment of benchmarks and provision of dedicated blood extraction equipment. First attempt blood draw occurred in 10 706 cases, representing a 96.2% success rate. In 427 (3.8%) cases, the samples were clotted requiring repeat collection. The overall rate of clotted specimens decreased from 4.8% in 2017 and 2018 to 2.4% in 2019, with odds ratios of 1.42 (95% confidence interval [CI] 1.13-1.78, p = .002), 1.46 (95% CI 1.17-1.81, p < .001) and 0.49 (95% CI 0.39-0.63, p < .001), respectively. The majority (87%-95%) of blood samples were by venepuncture using an intravenous (IV) catheter or the NeoSafe™ blood sampling device. Heel prick sampling was the second (2%-9%) most common method. Clotted samples were most frequently associated with needle use, 228 of 427 (53%), and IV cannula, 162 of 427 (38%), with odds ratios of 4.14 (95% CI 3.34-5.13, p < .001) and 3.11 (95% CI 2.51-3.86, p < .001), respectively. Our interventions over 3 years were associated with reduced rates of sample rejection due to clotting, and this led to improved patient experience through fewer repeated samplings. The insights gained from this project can help to improve patient care. Interventions that reduce the rate of blood sample rejection by clinical laboratories can lead to economic savings, timelier diagnostic and treatment decisions, and contribute to an improved quality care experience for all critical care patients, irrespective of age, by reducing the need for repeated phlebotomy and the risk of related complications.

Effect of Acupoint Stimulation on Controlling Pain from Heel Lance in Neonates: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To evaluate the effect of acupoint stimulation compared to other interventions on pain control in neonates who underwent heel lance, we searched for randomized controlled trials across six databases (CINAHL, Cochrane Library, EMBASE, Medline, PubMed, and Web of Science) published up to January 2023. Studies comparing acupoint stimulation and other interventions for controlling heel lance pain in neonates were included. These reports measured at least one of the following variables: pain score, crying time, oxygenation saturation, heart rate, respiration rate, and duration of the procedure. The data were independently extracted by two authors, and the PRISMA guidelines for study selection were followed. A total of 79 articles were screened, and 10 studies, with results on 813 neonates, were included in the final selection. The pain scores recorded during the heel lance procedure were not significantly different between the acupoint stimulation cohort and the control cohort (SMD of -0.26, 95% confidence interval (CI) from -0.52 to 0.01; p = 0.06; I2 = 68%). After processing the subgroup analyses, significant differences were found in the comparisons of acupuncture vs. usual care (SMD of -1.25, 95% CI from -2.23 to 0.27) and acupressure vs. usual care (SMD of -0.62, 95% CI from -0.96 to -0.28); nonsignificant differences were found in other comparisons. Our results demonstrate that acupoint stimulation may improve pain score during the heel lance procedure.

A Meta-analysis to Assess the Effectiveness of a Procedural Scale to Measure Pain in a Child Aged 0-1 Year

Background: Infant pain liability has been assessed in several studies; nonetheless, diminutive is recognized about the relevance and effectiveness of using one type of pain scale affording to the type of painful stimulus and the infant’s age. Purpose: Our purpose was to conduct a metaanalysis to assess and report on the efficiency of using the procedural pain scale to measure pain in a child aged 0-1 year using non-pharmacological interventions. Methods: A systematic search was performed up to October 2021 in PubMed and Cochrane Library. The current review enrolled randomized clinical trials (RCTs) according to PRISMA guidelines. Cochrane's risk of bias assessment was performed to assess the studies' quality and risk of bias. Meta-analyses were completed by calculating the standardized mean difference (SMD) at a 95% confidence interval (CI) using Review Manager Software. The review variables are: neonatal, pain, RCT and assessment. Results: The literature search returned 50 trials, but only 8 were involved in this meta-analysis. In most studies related to procedural pain (heel lance and vaccination), three commonly validated pain scales were used in all trials (neonatal infant pain scale NIPS, premature infant pain profile PIPP and neonatal pain, agitation and sedation scale NPASS. The 8 studies with 918 infant participants entered into analysis using effective pain scales (NIPS, PIPP and NPASS) to measure procedural pain effectively. Most studies used effective pain scales to measure procedural pain (NIPS, PIPP and NPASS). The meta-analysis showed a significant reduction in pain using NIPS, PIPP and NPASS tools. The most used was NIPS at 62.5%, followed by PIPP (25%) and NPASS (12.5%). The various interventions in studies reflected the strength of the used pain scale when assessing pain severity and supported the effect of non-pharmacological interventions (swaddling, mother holding and sucrose) in pain reduction compared with the control group (SMD 1.2, 95% CI -1.88 to -0.52, P =0.0005), I` = 95%, P&gt;0.00001. Conclusion: In this meta-analysis, it has been reported that the pain scales used were an appropriate measure of the outcome of pain reduction. The type and accuracy of the validation of pain scales are also essential when selecting tools for a clinical trial. Implications for Nursing: The pain scales used in studies are appropriate to assess pain when measuring procedural pain (heel lance and needle-related procedures such as vaccination). Pediatric nurses should take care of selecting appropriate tools to assess pain in children before managing the pain. Further, pediatric nurses should be aware of that the inconsistency about the best tool for children is related to several factors. One is related to matching the pain tool to the age group and type of pain

The role of time interval elimination on pain control of preterm infants by sucrose administration

The 2-min time interval of sucrose administration given before minor painful procedures in preterm infants is based on a few limited studies. We aimed to assess availability of sucrose analgesia in emergency states of minor procedural pain by eliminating the 2-min time interval prior to heel lance in preterm infants. The primary outcome was Premature Infants Pain Profile-Revised (PIPP-R) at 30 and 60s. Healthy 69 preterms undergoing a heel lance, who were assigned randomly to 1 of 2 groups, i.e., group I, with the 2-min time interval of per oral 24% sucrose given prior to heel lance, or group II, without a time interval of per oral 24% sucrose, were recruited. Premature Infants Pain Profile-Revised, crying incidence, duration, and heart rate at 30 and 60s following heel lance were the outcome measures in this single-center, randomized, prospective study. The 2 groups did not differ significantly in PIPP-R scores at 30s (6.63 vs. 6.32, p = .578) and 60s (5.80 vs. 5.38, p = .478). The crying incidence was similar between the 2 groups (p = .276). The median crying duration was 6s (range: 1-13s) in group I and 4.5s (range: 1-18s) in group II (p = .226). No significant differences in the heart rates between the 2 groups and the proportion of adverse events by time interval elimination were recorded. Eliminating the time interval did not decrease the analgesic effect of orally administered 24% sucrose given prior to heel lance. In emergency states of minor procedural pain, eliminating the 2-min time interval following sucrose administration is safe and efficacious in preterm infants.