Parental experiences of live video streaming technology in neonatal care in England: a qualitative study.

BACKGROUND: The use of bedside cameras in neonatal units facilitates livestreaming of infants to support parental and family bonding when they are unable to be physically present with their baby. This study aimed to explore the experiences of parents of infants previously admitted for neonatal care and who used live video streaming to view their baby in real-time. METHODS: Qualitative semi-structured interviews were conducted after discharge with parents of infants admitted for neonatal care on a tertiary level neonatal unit in the UK in 2021. Interviews were conducted virtually, transcribed verbatim and uploaded into NVivo V12 to facilitate analysis. Thematic analysis by two independent researchers was undertaken to identify themes representing the data. RESULTS: Seventeen participants took part in sixteen interviews. Thematic analysis identified 8 basic themes which were grouped into 3 organizational themes: (1) family integration of the baby including parent-infant, sibling-infant, and wider family-infant attachment facilitated through livestreaming, (2) implementation of the livestreaming service including communication, initial set up of the livestreaming service, and areas for improvement, and (3) parental control including emotional, and situational control. CONCLUSIONS: The use of livestreaming technology can provide parents with opportunities to integrate their baby into their wider family and friendship community and gain a sense of control over their baby's admission for neonatal care. On-going parental education around how to use, and what to expect from, livestreaming technology is required to minimise any potential distress from viewing their baby online.

Changes in Brain Tissue Oxygenation and Metabolism During Rewarming After Neonatal Encephalopathy are Related to Electrical Abnormality.

Hypoxic ischemic encephalopathy (HIE) leads to significant mortality and morbidity, and therapeutic hypothermia (TH) has become a standard of care following HIE. After TH, the body temperature is brought back to 37 °C. Early electroencephalography (EEG) is a reliable outcome biomarker following HIE. We hypothesized that changes in cerebral oxidative metabolism, measured as Δ[oxCCO], in relation to changes in brain tissue oxygenation (measured as Δ[HbD]) during rewarming will correlate with injury severity as evidenced on amplitude integrated EEG/EEG at initial presentation. Broadband near-infrared spectroscopy (NIRS) and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. All infants were monitored with video EEG telemetry using a standard neonatal montage. aEEG and EEG background was classified into mild, moderate and severely abnormal groups based on the background pattern. Two infants had mild, 6 infants had moderate and another 6 infants had severe abnormality at presentation. The relationship between [oxCCO] and [HbD] was evaluated between two groups of infants with abnormal electrical activity (mild vs moderate to severe). A significant difference was noted between the groups in the relationship between [oxCCO] and [HbD] (as r2) (p = 0.02). This result indicates that the mitochondrial injury and deranged oxidative metabolism persists in the moderate to severely abnormal group during rewarming.

Near-Infrared Spectroscopy Measured Cerebral Blood Flow from Spontaneous Oxygenation Changes in Neonatal Brain Injury.

Neonates with hypoxic-ischaemic (HI) brain injury were monitored using a broadband near-infrared spectroscopy (NIRS) system in the neonatal intensive care unit. The aim of this work is to use the NIRS cerebral oxygenation data (HbD = oxygenated-haemoglobin - deoxygenated-haemoglobin) combined with arterial saturation (SaO2) from pulse oximetry to calculate cerebral blood flow (CBF) based on the oxygen swing method, during spontaneous desaturation episodes. The method is based on Fick's principle and uses HbD as a tracer; when a sudden change in SaO2 occurs, the change in HbD represents a change in tracer concentration, and thus it is possible to estimate CBF. CBF was successfully calculated with broadband NIRS in 11 HIE infants (3 with severe injury) for 70 oxygenation events on the day of birth. The average CBF was 18.0 ± 12.7 ml 100 g-1 min-1 with a range of 4 ml 100 g-1 min-1 to 60 ml 100 g-1 min-1. For infants with severe HIE (as determined by magnetic resonance spectroscopy) CBF was significantly lower (p = 0.038, d = 1.35) than those with moderate HIE on the day of birth.

Core temperature after birth in babies with neonatal encephalopathy in a sub-Saharan African hospital setting.

KEY POINTS: Therapeutic hypothermia (HT) to 33.0-34.0°C for 72 h provides optimal therapy for infants with neonatal encephalopathy (NE) in high-resource settings. HT is not universally implemented in low- and middle-income countries as a result of both limited resources and evidence. Facilitated passive cooling, comprising infants being allowed to passively lower their body temperature in the days after birth, is an emerging practice in some West African neonatal units. In this observational study, we demonstrate that infants undergoing facilitated passive cooling in a neonatal unit in Accra, Ghana, achieve temperatures within the HT target range ∼20% of the 72 h. Depth of HT fluctuates and can be excessive, as well as not maintained, especially after 24 h. Sustained and deeper passive cooling was evident for severe NE and for those that died. It is important to prevent excessive cooling, to understand that severe NE babies cool more and to be aware of facilitated passive cooling with respect to the design of clinical trials in low- and mid-resource settings. ABSTRACT: Neonatal encephalopathy (NE) is a significant worldwide problem with the greatest burden in sub-Saharan Africa. Therapeutic hypothermia (HT), comprising the standard of care for infants with moderate-to-severe NE in settings with sophisticated intensive care, is not available to infants in many sub-Saharan African countries, including Ghana. We prospectively assessed the temperature response in relation to outcome in the 80 h after birth in a cohort of babies with NE undergoing 'facilitated passive cooling' at Korle Bu Teaching Hospital, Accra, Ghana. We hypothesized that NE infants demonstrate passive cooling. Thirteen infants (69% male) ≥36 weeks with moderate-to-severe NE were enrolled. Ambient mean ± SD temperature was 28.3 ± 0.7°C. Infant core temperature was 34.2 ± 1.2°C over the first 24 h and 35.0 ± 1.0°C over 80 h. Nadir mean temperature occurred at 15 h. Temperatures were within target range for HT with respect to 18 ± 14% of measurements within the first 72 h. Axillary temperature was 0.5 ± 0.2°C below core. Three infants died before discharge. Core temperature over 80 h for surviving infants was 35.3 ± 0.9°C and 33.96 ± 0.7°C for those that died (P = 0.043). Temperature profile negatively correlated with Thompson NE score on day 4 (r2  = 0.66): infants with a Thompson score of 0-6 had higher temperatures than those with a score of 7-15 (P = 0.021) and a score of 16+/deceased (P = 0.007). More severe NE was associated with lower core temperatures. Passive cooling is a physiological response after hypoxia-ischaemia; however, the potential neuroprotective effect of facilitated passive cooling is unknown. An awareness of facilitated passive cooling in babies with NE is important for the design of clinical trials of neuroprotection in low and mid resource settings.

The distribution of pain activity across the human neonatal brain is sex dependent.

In adults, there are differences between male and female structural and functional brain connectivity, specifically for those regions involved in pain processing. This may partly explain the observed sex differences in pain sensitivity, tolerance, and inhibitory control, and in the development of chronic pain. However, it is not known if these differences exist from birth. Cortical activity in response to a painful stimulus can be observed in the human neonatal brain, but this nociceptive activity continues to develop in the postnatal period and is qualitatively different from that of adults, partly due to the considerable cortical maturation during this time. This research aimed to investigate the effects of sex and prematurity on the magnitude and spatial distribution pattern of the long-latency nociceptive event-related potential (nERP) using electroencephalography (EEG). We measured the cortical response time-locked to a clinically required heel lance in 81 neonates born between 29 and 42 weeks gestational age (median postnatal age 4 days). The results show that heel lance results in a spatially widespread nERP response in the majority of newborns. Importantly, a widespread pattern is significantly more likely to occur in females, irrespective of gestational age at birth. This effect is not observed for the short latency somatosensory waveform in the same infants, indicating that it is selective for the nociceptive component of the response. These results suggest the early onset of a greater anatomical and functional connectivity reported in the adult female brain, and indicate the presence of pain-related sex differences from birth.

In Vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy Following Neonatal Stroke.

Neonatal stroke presents with features of encephalopathy and can result in significant morbidity and mortality. We investigated the cerebral metabolic and haemodynamic changes following neonatal stroke in a term infant at 24 h of life. Changes in oxidation state of cytochrome-c-oxidase (oxCCO) concentration were monitored along with changes in oxy- and deoxy- haemoglobin using a new broadband near-infrared spectroscopy (NIRS) system. Repeated transient changes in cerebral haemodynamics and metabolism were noted over a 3-h study period with decrease in oxyhaemoglobin (HbO2), deoxy haemoglobin (HHb) and oxCCO in both cerebral hemispheres without significant changes in systemic observations. A clear asymmetry was noted in the degree of change between the two cerebral hemispheres. Changes in cerebral oxygenation (measured as HbDiff=HbO2-HHb) and cerebral metabolism (measured as oxCCO) were highly coupled on the injured side of the brain.

Interrelationship Between Broadband NIRS Measurements of Cerebral Cytochrome C Oxidase and Systemic Changes Indicates Injury Severity in Neonatal Encephalopathy.

Perinatal hypoxic ischaemic encephalopathy (HIE) is associated with severe neurodevelopmental problems and mortality. There is a clinical need for techniques to provide cotside assessment of the injury extent. This study aims to use non-invasive cerebral broadband near-infrared spectroscopy (NIRS) in combination with systemic physiology to assess the severity of HIE injury. Broadband NIRS is used to measure the changes in haemodynamics, oxygenation and the oxidation state of cytochrome c oxidase (oxCCO). We used canonical correlation analysis (CCA), a multivariate statistical technique, to measure the relationship between cerebral broadband NIRS measurements and systemic physiology. A strong relationship between the metabolic marker, oxCCO, and systemic changes indicated severe brain injury; if more than 60 % of the oxCCO signal could be explained by the systemic variations, then the neurodevelopmental outcome was poor. This boundary has high sensitivity and specificity (100 and 83 %, respectively). Broadband NIRS measured concentration changes of the oxidation state of cytochrome c oxidase has the potential to become a useful cotside tool for assessment of injury severity following hypoxic ischaemic brain injury.

Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury.

Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values <0.5, 0.5-1, >1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming.

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain.

AIM: Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. METHODS: We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. RESULTS: Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. CONCLUSION: Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain.

Health Care Professionals' and Parents' Perspectives on the Use of AI for Pain Monitoring in the Neonatal Intensive Care Unit: Multisite Qualitative Study.

BACKGROUND: The use of artificial intelligence (AI) for pain assessment has the potential to address historical challenges in infant pain assessment. There is a dearth of information on the perceived benefits and barriers to the implementation of AI for neonatal pain monitoring in the neonatal intensive care unit (NICU) from the perspective of health care professionals (HCPs) and parents. This qualitative analysis provides novel data obtained from 2 large tertiary care hospitals in Canada and the United Kingdom. OBJECTIVE: The aim of the study is to explore the perspectives of HCPs and parents regarding the use of AI for pain assessment in the NICU. METHODS: In total, 20 HCPs and 20 parents of preterm infants were recruited and consented to participate from February 2020 to October 2022 in interviews asking about AI use for pain assessment in the NICU, potential benefits of the technology, and potential barriers to use. RESULTS: The 40 participants included 20 HCPs (17 women and 3 men) with an average of 19.4 (SD 10.69) years of experience in the NICU and 20 parents (mean age 34.4, SD 5.42 years) of preterm infants who were on average 43 (SD 30.34) days old. Six themes from the perspective of HCPs were identified: regular use of technology in the NICU, concerns with regard to AI integration, the potential to improve patient care, requirements for implementation, AI as a tool for pain assessment, and ethical considerations. Seven parent themes included the potential for improved care, increased parental distress, support for parents regarding AI, the impact on parent engagement, the importance of human care, requirements for integration, and the desire for choice in its use. A consistent theme was the importance of AI as a tool to inform clinical decision-making and not replace it. CONCLUSIONS: HCPs and parents expressed generally positive sentiments about the potential use of AI for pain assessment in the NICU, with HCPs highlighting important ethical considerations. This study identifies critical methodological and ethical perspectives from key stakeholders that should be noted by any team considering the creation and implementation of AI for pain monitoring in the NICU.

Cortical activity evoked by an acute painful tissue-damaging stimulus in healthy adult volunteers.

Everyday painful experiences are usually single events accompanied by tissue damage, and yet most experimental studies of cutaneous nociceptive processing in the brain use repeated laser, thermal, or electrical stimulations that do not damage the skin. In this study the nociceptive activity in the brain evoked by tissue-damaging skin lance was analyzed with electroencephalography (EEG) in 20 healthy adult volunteers (13 men and 7 women) aged 21-40 yr. Time-frequency analysis of the evoked activity revealed a distinct late event-related vertex potential (lance event-related potential, LERP) at 100-300 ms consisting of a phase-locked energy increase between 1 and 20 Hz (delta-beta bands). A pairwise comparison between lance and sham control stimulation also revealed a period of ultralate stronger desynchronization after lance in the delta band (1-5 Hz). Skin application of mustard oil before lancing, which sensitizes a subpopulation of nociceptors expressing the cation channel TRPA1, did not affect the ultralate desynchronization but reduced the phase-locked energy increase in delta and beta bands, suggesting a central interaction between different modalities of nociceptive inputs. Verbal descriptor screening of individual pain experience revealed that lance pain is predominantly due to Aδ fiber activation, but when individuals describe lances as C fiber mediated, an ultralate delta band event-related desynchronization occurs in the brain-evoked activity. We conclude that pain evoked by acute tissue damage is associated with distinct Aδ and C fiber-mediated patterns of synchronization and desynchronization of EEG oscillations in the brain.

Clinical value of cortical bursting in preterm infants with intraventricular haemorrhage.

BACKGROUND: In healthy preterm infants, cortical burst rate and temporal dynamics predict important measures such as brain growth. We hypothesised that in preterm infants with germinal matrix-intraventricular haemorrhage (GM-IVH), cortical bursting could provide prognostic information. AIMS: We determined how cortical bursting was influenced by the injury, and whether this was related to developmental outcome. STUDY DESIGN: Single-centre retrospective cohort study at University College London Hospitals, UK. SUBJECTS: 33 infants with GM-IVH ≥ grade II (median gestational age: 25 weeks). OUTCOME MEASURES: We identified 47 EEGs acquired between 24 and 40 weeks corrected gestational age as part of routine clinical care. In a subset of 33 EEGs from 25 infants with asymmetric injury, we used the least-affected hemisphere as an internal comparison. We tested whether cortical burst rate predicted survival without severe impairment (median 2 years follow-up). RESULTS: In asymmetric injury, cortical burst rate was lower over the worst- than least-affected hemisphere, and bursts over the worst-affected hemisphere were less likely to immediately follow bursts over the least-affected hemisphere than vice versa. Overall, burst rate was lower in cases of GM-IVH with parenchymal involvement, relative to milder structural injury grades. Higher burst rate modestly predicted survival without severe language (AUC 0.673) or motor impairment (AUC 0.667), which was partly mediated by structural injury grade. CONCLUSIONS: Cortical bursting can index the functional injury after GM-IVH: perturbed burst initiation (rate) and propagation (inter-hemispheric dynamics) likely reflect associated grey matter and white matter damage. Higher cortical burst rate is reassuring for a positive outcome.

Feasibility of smartphone colorimetry of the face as an anaemia screening tool for infants and young children in Ghana.

BACKGROUND: Anaemia affects approximately a quarter of the global population. When anaemia occurs during childhood, it can increase susceptibility to infectious diseases and impair cognitive development. This research uses smartphone-based colorimetry to develop a non-invasive technique for screening for anaemia in a previously understudied population of infants and young children in Ghana. METHODS: We propose a colorimetric algorithm for screening for anaemia which uses a novel combination of three regions of interest: the lower eyelid (palpebral conjunctiva), the sclera, and the mucosal membrane adjacent to the lower lip. These regions are chosen to have minimal skin pigmentation occluding the blood chromaticity. As part of the algorithm development, different methods were compared for (1) accounting for varying ambient lighting, and (2) choosing a chromaticity metric for each region of interest. In comparison to some prior work, no specialist hardware (such as a colour reference card) is required for image acquisition. RESULTS: Sixty-two patients under 4 years of age were recruited as a convenience clinical sample in Korle Bu Teaching Hospital, Ghana. Forty-three of these had quality images for all regions of interest. Using a naïve Bayes classifier, this method was capable of screening for anaemia (<11.0g/dL haemoglobin concentration) vs healthy blood haemoglobin concentration (≥11.0g/dL) with a sensitivity of 92.9% (95% CI 66.1% to 99.8%), a specificity of 89.7% (72.7% to 97.8%) when acting on unseen data, using only an affordable smartphone and no additional hardware. CONCLUSION: These results add to the body of evidence suggesting that smartphone colorimetry is likely to be a useful tool for making anaemia screening more widely available. However, there remains no consensus on the optimal method for image preprocessing or feature extraction, especially across diverse patient populations.

Clinical thresholds in pain-related facial activity linked to differences in cortical network activation in neonates.

ABSTRACT: In neonates, a noxious stimulus elicits pain-related facial expression changes and distinct brain activity as measured by electroencephalography, but past research has revealed an inconsistent relationship between these responses. Facial activity is the most commonly used index of neonatal pain in clinical settings, with clinical thresholds determining if analgesia should be provided; however, we do not know if these thresholds are associated with differences in how the neonatal brain processes a noxious stimulus. The objective of this study was to examine whether subclinical vs clinically significant levels of pain-related facial activity are related to differences in the pattern of nociceptive brain activity in preterm and term neonates. We recorded whole-head electroencephalography and video in 78 neonates (0-14 days postnatal age) after a clinically required heel lance. Using an optimal constellation of Neonatal Facial Coding System actions (brow bulge, eye squeeze, and nasolabial furrow), we compared the serial network engagement (microstates) between neonates with and without clinically significant pain behaviour. Results revealed a sequence of nociceptive cortical network activation that was independent of pain-related behavior; however, a separate but interleaved sequence of early activity was related to the magnitude of the immediate behavioural response. Importantly, the degree of pain-related behavior is related to how the brain processes a stimulus and not simply the degree of cortical activation. This suggests that neonates who exhibit clinically significant pain behaviours process the stimulus differently and that neonatal pain-related behaviours reflect just a portion of the overall cortical pain response.

A developmental shift in habituation to pain in human neonates.

Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates.

Widespread nociceptive maps in the human neonatal somatosensory cortex.

Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n = 32) using multioptode functional near-infrared spectroscopy (fNIRS). Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin concentration (Δ[HbO]), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour.

Neonatal jaundice in Ghanaian children: Assessing maternal knowledge, attitude, and perceptions.

BACKGROUND: Neonatal jaundice (NNJ) is a major cause of preventable childhood mortality and long-term impairment especially in countries with significant prevalence of the inherited condition, glucose-6-phosphate dehydrogenase (G6PD) defect. In Ghana, routine screening of pregnant women for G6PD defect is standard care. Prevention of poor health outcomes from NNJ is contingent on population health literacy and early diagnosis. As part of a project to evaluate a screening tool for NNJ, we assessed the knowledge, attitude, and perceptions of Ghanaian mothers on NNJ at baseline. METHODS: Using a cross-sectional design, mothers attending antenatal and postnatal clinics at 3 selected health facilities in 2 geographical regions of Ghana were interviewed. Data on mothers' understanding, perceptions, beliefs, and actions towards NNJ were evaluated. Chi-square test was used to determine the association between selected maternal characteristics and knowledge, attitude, and perception to NNJ. RESULTS: Of the 504 mothers interviewed, 428(85.4%) had heard about NNJ, 346 (68.7%) said the earliest signs are seen in the eyes, 384(76.2%) knew NNJ may be harmful and 467(92.7%) recommended seeking healthcare for the jaundiced newborn. None of the women knew about G6PD or their G6PD status following antenatal screening. Most did not know the signs/symptoms of severe NNJ. Of the 15 mothers who had had a jaundiced neonate, cost was the most perceived (8 out of 15) barrier to accessing health care. There were significant associations (p-value ≤ 0.05) between maternal age, educational level, and knowledge of NNJ. CONCLUSION: Despite the high level of awareness of NNJ, gaps still exit in the knowledge, attitudes and perceptions of mothers concerning NNJ. Improving education of women about the causes, symptoms/signs, and the role of G6PD in severe NNJ is recommended. Addressing barriers to accessing healthcare for the jaundiced infant may enhance timely management of NNJ and reduce the associated complications and mortality.

Validating a Sclera-Based Smartphone Application for Screening Jaundiced Newborns in Ghana.

OBJECTIVES: Reducing the burden of bilirubin-induced neurologic complications in low-resource countries requires reliable and accessible screening tools. We sought to optimize and validate a sclera-based smartphone application, Neonatal Scleral-Conjunctival Bilirubin (neoSCB), for screening neonatal jaundice. METHODS: Using a cross-sectional design, consecutive eligible infants (aged 0-28 days, in the hospital, not critically ill) were enrolled in Ghana from March 2019 to April 2020. Jaundice screening was performed with neoSCB (Samsung Galaxy S8) to quantify SCB and JM-105 (Dräger) for transcutaneous bilirubin (TcB). Screening values were compared with total serum bilirubin (TSB) measured at the point of care. RESULTS: Overall, 724 infants participated in the optimization and validation phases of the study. The analysis for validation included 336 infants with no previous treatment of jaundice. Single neoSCB image captures identified infants with TSB >14.62 mg/dL (250 µmol/L) with reasonably high sensitivity, specificity, and receiver operating characteristic area under the curve at 0.94 (95% confidence interval [CI], 0.91 to 0.97), 0.73 (95% CI, 0.68 to 0.78), and 0.90, respectively. These findings were comparable to the sensitivity and specificity of JM-105 (0.96 [95% CI, 0.90 to 0.99] and 0.81 [95% CI, 0.76 to 0.86], respectively). The TcB/TSB had a larger correlation coefficient (r = 0.93; P < .01) than SCB/TSB (r = 0.78; P < .01). Performance of both devices was lower in infants with previous phototherapy (n = 231). CONCLUSIONS: The diagnostic performance of neoSCB was comparable to JM-105 and is a potential, affordable, contact-free screening tool for neonatal jaundice.

Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial.

BACKGROUND: Many infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants. METHODS: In this double-blind, randomised controlled trial, 59 newborn infants at University College Hospital (London, UK) were randomly assigned to receive 0·5 mL 24% sucrose solution or 0·5 mL sterile water 2 min before undergoing a clinically required heel lance. Randomisation was by a computer-generated randomisation code, and researchers, clinicians, participants, and parents were masked to the identity of the solutions. The primary outcome was pain-specific brain activity evoked by one time-locked heel lance, recorded with electroencephalography and identified by principal component analysis. Secondary measures were baseline behavioural and physiological measures, observational pain scores (PIPP), and spinal nociceptive reflex withdrawal activity. Data were analysed per protocol. This study is registered, number ISRCTN78390996. FINDINGS: 29 infants were assigned to receive sucrose and 30 to sterilised water; 20 and 24 infants, respectively, were included in the analysis of the primary outcome measure. Nociceptive brain activity after the noxious heel lance did not differ significantly between infants who received sucrose and those who received sterile water (sucrose: mean 0·10, 95% CI 0·04-0·16; sterile water: mean 0·08, 0·04-0·12; p=0·46). No significant difference was recorded between the sucrose and sterile water groups in the magnitude or latency of the spinal nociceptive reflex withdrawal recorded from the biceps femoris of the stimulated leg. The PIPP score was significantly lower in infants given sucrose than in those given sterile water (mean 5·8, 95% CI 3·7-7·8 vs 8·5, 7·3-9·8; p=0·02) and significantly more infants had no change in facial expression after sucrose administration (seven of 20 [35%] vs none of 24; p<0·0001). INTERPRETATION: Our data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits, and therefore might not be an effective analgesic drug. The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief. FUNDING: Medical Research Council.

Sleep-wake regulation in preterm and term infants.

STUDY OBJECTIVES: In adults, wakefulness can be markedly prolonged at the expense of sleep, e.g. to stay vigilant in the presence of a stressor. These extra-long wake bouts result in a heavy-tailed distribution (highly right-skewed) of wake but not sleep durations. In infants, the relative importance of wakefulness and sleep are reversed, as sleep is necessary for brain maturation. Here, we tested whether these developmental pressures are associated with the unique regulation of sleep-wake states. METHODS: In 175 infants of 28-40 weeks postmenstrual age (PMA), we monitored sleep-wake states using electroencephalography and behavior. We constructed survival models of sleep-wake bout durations and the effect of PMA and other factors, including stress (salivary cortisol), and examined whether sleep is resilient to nociceptive perturbations (a clinically necessary heel lance). RESULTS: Wake durations followed a heavy-tailed distribution as in adults and lengthened with PMA and stress. However, differently from adults, active sleep durations also had a heavy-tailed distribution, and with PMA, these shortened and became vulnerable to nociception-associated awakenings. CONCLUSIONS: Sleep bouts are differently regulated in infants, with especially long active sleep durations that could consolidate this state's maturational functions. Curtailment of sleep by stress and nociception may be disadvantageous, especially for preterm infants given the limited value of wakefulness at this age. This could be addressed by environmental interventions in the future.