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.

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.

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.

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.

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.

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.

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.

Prognostic value of neonatal EEG following therapeutic hypothermia in survivors of hypoxic-ischemic encephalopathy.

OBJECTIVE: Early prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes. METHODS: We identified 41 surviving infants who received therapeutic hypothermia for HIE (classification at hospital discharge: 19 mild, 18 moderate, 4 severe) and had 9-channel electroencephalography (EEG) recordings as part of their routine care. We correlated burst power with Bayley-III cognitive, motor and language scores at median 24 months. To examine whether EEG offered additional prognostic information, we controlled for structural MRI findings. RESULTS: Higher power of central and occipital cortical bursts predicted worse cognitive and language outcomes, and higher power of central cortical bursts predicted worse motor outcome, all independently of structural MRI findings. CONCLUSIONS: Clinical EEG after postnatal day 3 may provide additional prognostic information by indexing persistent active mechanisms that either support recovery or exacerbate brain damage, especially in infants with less severe encephalopathy. SIGNIFICANCE: These findings could allow for the effect of clinical interventions in the neonatal period to be studied instantaneously in the future.

The impact of parental contact upon cortical noxious-related activity in human neonates.

BACKGROUND: Neonates display strong behavioural, physiological and cortical responses to tissue-damaging procedures. Parental contact can successfully regulate general behavioural and physiological reactivity of the infant, but it is not known whether it can influence noxious-related activity in the brain. Brain activity is highly dependent upon maternal presence in animal models, and therefore this could be an important contextual factor in human infant pain-related brain activity. METHODS: Global topographic analysis was used to identify the presence and inter-group differences in noxious-related activity in three separate parental contexts. EEG was recorded during a clinically required heel lance in three age and sex-matched groups of neonates (a) while held by a parent in skin-to-skin (n = 9), (b) while held by a parent with clothing (n = 9) or (c) not held at all, but in individualized care (n = 9). RESULTS: The lance elicited a sequence of 4-5 event-related potentials (ERPs), including the noxious ERP (nERP), which was smallest for infants held skin-to-skin and largest for infants held with clothing (p=0.016). The nERP was then followed by additional and divergent long-latency ERPs (> 750 ms post-lance), not previously described, in each of the groups, suggesting the engagement of different higher level cortical processes depending on parental contact. CONCLUSIONS: These results show the importance of considering contextual factors in determining infant brain activity and reveal the powerful influence of parental contact upon noxious-related activity across the developing human brain. SIGNIFICANCE: This observational study found that the way in which the neonatal brain processes a noxious stimulus is altered by the type of contact the infant has with their mother. Specifically, being held in skin-to-skin reduces the magnitude of noxious-related cortical activity. This work has also shown that different neural mechanisms are engaged depending on the mother/infant context, suggesting maternal contact can change how a baby's brain processes a noxious stimulus.

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.

Long-range temporal organisation of limb movement kinematics in human neonates.

OBJECTIVE: Movement provides crucial sensorimotor information to the developing brain, evoking somatotopic cortical EEG activity. Indeed, temporal-spatial organisation of these movements, including a diverse repertoire of accelerations and limb combinations (e.g. unilateral progressing to bilateral), predicts positive sensorimotor outcomes. However, in current clinical practice, movements in human neonates are qualitatively characterised only during brief periods (a few minutes) of wakefulness, meaning that the vast majority of sensorimotor experience remains unsampled. Here our objective was to quantitatively characterise the long-range temporal organisation of the full repertoire of newborn movements, over multi-hour recordings. METHODS: We monitored motor activity across 2-4 h in 11 healthy newborn infants (median 1 day old), who wore limb sensors containing synchronised tri-axial accelerometers and gyroscopes. Movements were identified using acceleration and angular velocity, and their organisation across the recording was characterised using cluster analysis and spectral estimation. RESULTS: Movement occurrence was periodic, with a 1-hour cycle. Peaks in movement occurrence were associated with higher acceleration, and a higher proportion of movements being bilateral. CONCLUSIONS: Neonatal movement occurrence is cyclical, with periods consistent with sleep-wake behavioural architecture. Movement kinematics are organised by these fluctuations in movement occurrence. Recordings that exceed 1-hour are necessary to capture the long-range temporal organisation of the full repertoire of newborn limb movements. SIGNIFICANCE: Future work should investigate the prognostic value of combining these movement recordings with synchronised EEG, in at-risk infants.

Cerebral Near Infrared Spectroscopy Monitoring in Term Infants With Hypoxic Ischemic Encephalopathy-A Systematic Review.

Background: Neonatal hypoxic ischemic encephalopathy (HIE) remains a significant cause of mortality and morbidity worldwide. Cerebral near infrared spectroscopy (NIRS) can provide cot side continuous information about changes in brain hemodynamics, oxygenation and metabolism in real time. Objective: To perform a systematic review of cerebral NIRS monitoring in term and near-term infants with HIE. Search Methods: A systematic search was performed in Ovid EMBASE and Medline database from inception to November 2019. The search combined three broad categories: measurement (NIRS monitoring), disease condition [hypoxic ischemic encephalopathy (HIE)] and subject category (newborn infants) using a stepwise approach as per PRISMA guidance. Selection Criteria: Only human studies published in English were included. Data Collection and Analysis: Two authors independently selected, assessed the quality, and extracted data from the studies for this review. Results: Forty-seven studies on term and near-term infants following HIE were identified. Most studies measured multi-distance NIRS based cerebral tissue saturation using monitors that are referred to as cerebral oximeters. Thirty-nine studies were published since 2010; eight studies were published before this. Fifteen studies reviewed the neurodevelopmental outcome in relation to NIRS findings. No randomized study was identified. Conclusion: Commercial NIRS cerebral oximeters can provide important information regarding changes in cerebral oxygenation and hemodynamics following HIE and can be particularly helpful when used in combination with other neuromonitoring tools. Optical measurements of brain metabolism using broadband NIRS and cerebral blood flow using diffuse correlation spectroscopy add additional pathophysiological information. Further randomized clinical trials and large observational studies are necessary with proper study design to assess the utility of NIRS in predicting neurodevelopmental outcome and guiding therapeutic interventions.

Smartphone screening for neonatal jaundice via ambient-subtracted sclera chromaticity.

Jaundice is a major cause of mortality and morbidity in the newborn. Globally, early identification and home monitoring are significant challenges in reducing the incidence of jaundice-related neurological damage. Smartphone cameras are promising as colour-based screening tools as they are low-cost, objective and ubiquitous. We propose a novel smartphone method to screen for neonatal jaundice by imaging the sclera. It does not rely on colour calibration cards or accessories, which may facilitate its adoption at scale and in less economically developed regions. Our approach is to explicitly address three confounding factors in relating colour to jaundice: (1) skin pigmentation, (2) ambient light, and (3) camera spectral response. (1) The variation in skin pigmentation is avoided by imaging the sclera. (2) With the smartphone screen acting as an illuminating flash, a flash/ no-flash image pair is captured using the front-facing camera. The contribution of ambient light is subtracted. (3) In principle, this permits a device- and ambient-independent measure of sclera chromaticity following a one-time calibration. We introduce the concept of Scleral-Conjunctival Bilirubin (SCB), in analogy with Transcutaneous Bilirubin (TcB). The scleral chromaticity is mapped to an SCB value. A pilot study was conducted in the UCL Hospital Neonatal Care Unit (n = 37). Neonates were imaged using a specially developed app concurrently with having a blood test for total serum bilirubin (TSB). The better of two models for SCB based on ambient-subtracted sclera chromaticity achieved r = 0.75 (p<0.01) correlation with TSB. Ambient subtraction improved chromaticity estimates in proof-of-principle laboratory tests and screening performance within our study sample. Using an SCB decision threshold of 190µmol/L, the sensitivity was 100% (specificity 61%) in identifying newborns with TSB>250µmol/L (area under receiver operating characteristic curve, AUROC, 0.86), and 92% (specificity 67%) in identifying newborns with TSB>205µmol/L (AUROC 0.85). These results are comparable to modern transcutaneous bilirubinometers.

Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants.

There is increasing evidence that long-term outcomes for infants born prematurely are adversely affected by repeated exposure to noxious procedures. These interventions vary widely, for example, in the extent of damage caused and duration. Neonatal intensive care unit (NICU) procedures are therefore likely to each contribute differently to the overall pain burden of individual neonates, ultimately having a different impact on their development. For researchers to quantify the procedural pain burden experienced by infants on NICU, we aimed to estimate the pain severity of common NICU procedures using published pain scores. We extracted pain scores over the first minute (pain reactivity) from the literature, using 59 randomized controlled trials for 15 different procedures. Hierarchical cluster analysis of average pain scores resulted in 5 discrete severity groups; mild (n = 1), mild to moderate (n = 3), moderate (n = 7), severe (n = 3), and very severe (n = 1). The estimate of the severity of individual procedures provided new insight into infant pain reactivity which is not always directly related to the invasiveness and duration of a procedure; thus, both heel lance and skin tape removal are moderately painful procedures. This estimate of procedural pain severity, based on pain reactivity scores, provides a novel platform for retrospective quantification of an individual neonate's pain burden due to NICU procedures. The addition of measures that reflect the recovery from each procedure, such as brain activity and behavioural regulation, would further improve estimates of the pain burden of neonatal intensive care.

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.

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.

Altered cortical processing of somatosensory input in pre-term infants who had high-grade germinal matrix-intraventricular haemorrhage.

High-grade (large) germinal matrix-intraventricular haemorrhage (GM-IVH) is one of the most common causes of somatomotor neurodisability in pre-term infants. GM-IVH presents during the first postnatal week and can impinge on somatosensory circuits resulting in aberrant somatosensory cortical events straight after injury. Subsequently, somatosensory circuits undergo significant plastic changes, sometimes allowing the reinstatement of a somatosensory cortical response. However, it is not known whether this restructuring results in a full recovery of somatosensory functions. To investigate this, we compared somatosensory responses to mechanical stimulation measured with 18-channels EEG between infants who had high-grade GM-IVH (with ventricular dilatation and/or intraparenchymal lesion; n = 7 studies from 6 infants; mean corrected gestational age = 33 weeks; mean postnatal age = 56 days) and age-matched controls (n = 9 studies from 8 infants; mean corrected gestational age = 32 weeks; mean postnatal age = 36 days). We showed that infants who had high-grade GM-IVH did not recruit the same cortical source configuration following stimulation of the foot, but their response to stimulation of the hand resembled that of controls. These results show that somatosensory cortical circuits are reinstated in infants who had GM-IVH, during the several weeks after injury, but remain different from those of infants without brain injury. An important next step will be to investigate whether these evidences of neural reorganisation predict neurodevelopmental outcome.

Event-related potentials following contraction of respiratory muscles in pre-term and full-term infants.

OBJECTIVE: Involuntary isolated body movements are prominent in pre-term and full-term infants. Proprioceptive and tactile afferent feedback following limb muscle contractions is associated with somatotopic EEG responses. Involuntary contractions of respiratory muscles, primarily the diaphragm - hiccups - are also frequent throughout the human perinatal period during active behavioural states. Here we tested whether diaphragm contraction provides afferent input to the developing brain, as following limb muscle contraction. METHODS: In 13 infants on the neonatal ward (30-42 weeks corrected gestational age), we analysed EEG activity (18-electrode recordings in six subjects; 17-electrode recordings in five subjects; 16-electrode recordings in two subjects), time-locked to diaphragm contractions (n = 1316) recorded with a movement transducer affixed to the trunk. RESULTS: All bouts of hiccups occurred during wakefulness or active sleep. Each diaphragm contraction evoked two initial event-related potentials with negativity predominantly across the central region, and a third event-related potential with positivity maximal across the central region. CONCLUSIONS: Involuntary contraction of the diaphragm can be encoded by the brain from as early as ten weeks prior to the average time of birth. SIGNIFICANCE: Hiccups - frequently observed in neonates - can provide afferent input to developing sensory cortices in pre-term and full-term infants.