Machine Learning-Derived Active Sleep as an Early Predictor of White Matter Development in Preterm Infants.

White matter dysmaturation is commonly seen in preterm infants admitted to the neonatal intensive care unit (NICU). Animal research has shown that active sleep is essential for early brain plasticity. This study aimed to determine the potential of active sleep as an early predictor for subsequent white matter development in preterm infants. Using heart and respiratory rates routinely monitored in the NICU, we developed a machine learning-based automated sleep stage classifier in a cohort of 25 preterm infants (12 females). The automated classifier was subsequently applied to a study cohort of 58 preterm infants (31 females) to extract active sleep percentage over 5-7 consecutive days during 29-32 weeks of postmenstrual age. Each of the 58 infants underwent high-quality T2-weighted magnetic resonance brain imaging at term-equivalent age, which was used to measure the total white matter volume. The association between active sleep percentage and white matter volume was examined using a multiple linear regression model adjusted for potential confounders. Using the automated classifier with a superior sleep classification performance [mean area under the receiver operating characteristic curve (AUROC) = 0.87, 95% CI 0.83-0.92], we found that a higher active sleep percentage during the preterm period was significantly associated with an increased white matter volume at term-equivalent age [ß = 0.31, 95% CI 0.09-0.53, false discovery rate (FDR)-adjusted p-value = 0.021]. Our results extend the positive association between active sleep and early brain development found in animal research to human preterm infants and emphasize the potential benefit of sleep preservation in the NICU setting.

Effect of Systemic Hydrocortisone on Brain Abnormalities and Regional Brain Volumes in Ventilator-dependent Infants Born Preterm: Substudy of the SToP-BPD Study.

OBJECTIVE: To evaluate whether a high cumulative dose of systemic hydrocortisone affects brain development compared with placebo when initiated between 7 and 14 days after birth in ventilated infants born preterm. STUDY DESIGN: A double-blind, placebo-controlled, randomized trial was conducted in 16 neonatal intensive care units among infants born at <30 weeks of gestation or with a birth weight of <1250 g who were ventilator-dependent in the second week after birth. Three centers performed MRI at term-equivalent age. Brain injury was assessed on MRI using the Kidokoro scoring system and compared between the 2 treatment groups. Both total and regional brain volumes were calculated using an automatic segmentation method and compared using multivariable regression analysis adjusted for baseline variables. RESULTS: From the 3 centers, 78 infants participated in the study and 59 had acceptable MRI scans (hydrocortisone group, n = 31; placebo group, n = 28). Analyses of the median global brain abnormality score of the Kidokoro score showed no difference between the hydrocortisone and placebo groups (median, 7; IQR, 5-9 vs median, 8, IQR, 4-10, respectively; P = .92). In 39 infants, brain tissue volumes were measured, showing no differences in the adjusted mean total brain tissue volumes, at 352 ± 32 mL in the hydrocortisone group and 364 ± 51 mL in the placebo group (P = .80). CONCLUSIONS: Systemic hydrocortisone started in the second week after birth in ventilator-dependent infants born very preterm was not found to be associated with significant differences in brain development compared with placebo treatment. TRIAL REGISTRATION: The SToP-BPD study was registered with the Netherlands Trial Register (NTR2768; registered on 17 February 2011; https://www.trialregister.nl/trial/2640) and the European Union Clinical Trials Register (EudraCT, 2010-023777-19; registered on 2 November 2010; https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023777-19/NL).

Sleep as a driver of pre- and postnatal brain development.

In 1966, Howard Roffwarg proposed the ontogenic sleep hypothesis, relating neural plasticity and development to rapid eye movement (REM) sleep, a hypothesis that current fetal and neonatal sleep research is still exploring. Recently, technological advances have enabled researchers to automatically quantify neonatal sleep architecture, which has caused a resurgence of research in this field as attempts are made to further elucidate the important role of sleep in pre- and postnatal brain development. This article will review our current understanding of the role of sleep as a driver of brain development and identify possible areas for future research. IMPACT: The evidence to date suggests that Roffwarg's ontogenesis hypothesis of sleep and brain development is correct. A better understanding of the relationship between sleep and the development of functional connectivity is needed. Reliable, non-invasive tools to assess sleep in the NICU and at home need to be tested in a real-world environment and the best way to promote healthy sleep needs to be understood before clinical trials promoting and optimizing sleep quality in neonates could be undertaken.

Developmental anatomy of the thalamus, perinatal lesions, and neurological development.

The thalamic nuclei develop before a viable preterm age. GABAergic neuronal migration is especially active in the third trimester. Thalamic axons meet cortical axons during subplate activation and create the definitive cortical plate in the second and third trimesters. Default higher-order cortical driver connections to the thalamus are then replaced by the maturing sensory networks, in a process that is driven by first-order thalamic neurons. Surface electroencephalographic activity, generated first in the subplate and later in the cortical plate, gradually show oscillations based on the interaction of the cortex with thalamus, which is controlled by the thalamic reticular nucleus. In viable newborn infants, in addition to sensorimotor networks, the thalamus already contributes to visual, auditory, and pain processing, and to arousal and sleep. Isolated thalamic lesions may present as clinical seizures. In addition to asphyxia and stroke, infection and network injury are also common. Cranial ultrasound can be used to classify neonatal thalamic injuries based on functional parcelling of the mature thalamus. We provide ample illustration and a detailed description of the impact of neonatal focal thalamic injury on neurological development, and discuss the potential for neuroprotection based on thalamocortical plasticity.

Characterising the motion and cardiorespiratory interaction of preterm infants can improve the classification of their sleep state.

AIM: This study aimed to classify quiet sleep, active sleep and wake states in preterm infants by analysing cardiorespiratory signals obtained from routine patient monitors. METHODS: We studied eight preterm infants, with an average postmenstrual age of 32.3 ± 2.4 weeks, in a neonatal intensive care unit in the Netherlands. Electrocardiography and chest impedance respiratory signals were recorded. After filtering and R-peak detection, cardiorespiratory features and motion and cardiorespiratory interaction features were extracted, based on previous research. An extremely randomised trees algorithm was used for classification and performance was evaluated using leave-one-patient-out cross-validation and Cohen's kappa coefficient. RESULTS: A sleep expert annotated 4731 30-second epochs (39.4 h) and active sleep, quiet sleep and wake accounted for 73.3%, 12.6% and 14.1% respectively. Using all features, and the extremely randomised trees algorithm, the binary discrimination between active and quiet sleep was better than between other states. Incorporating motion and cardiorespiratory interaction features improved the classification of all sleep states (kappa 0.38 ± 0.09) than analyses without these features (kappa 0.31 ± 0.11). CONCLUSION: Cardiorespiratory interactions contributed to detecting quiet sleep and motion features contributed to detecting wake states. This combination improved the automated classifications of sleep states.

Synthetic magnetic resonance-based relaxometry and brain volume: cutoff values for predicting neurocognitive outcomes in very preterm infants.

BACKGROUND: Early neurorehabilitation can enhance neurocognitive outcomes in very preterm infants (<32 weeks), and conventional magnetic resonance imaging (MRI) is commonly used to assess neonatal brain injury; however, the predictive value for neurodevelopmental delay is limited. Timely predictive quantitative biomarkers are needed to improve early identification and management of infants at risk of neurodevelopmental delay. OBJECTIVE: To evaluate the potential of quantitative synthetic MRI measurements at term-equivalent age as predictive biomarkers of neurodevelopmental impairment and establish practical cutoff values to guide clinical decision-making. MATERIALS AND METHODS: This retrospective study included 93 very preterm infants who underwent synthetic MRI at term-equivalent age between January 2017 and September 2020. Clinical outcomes were assessed using the Bayley-III scale of infant development (mean age 2.1 years). The predictive value for impaired development was analyzed using receiver operating characteristic curves for synthetic MRI-based volumetry and T1 and T2 relaxation measurements. RESULTS: The T1 relaxation time in the posterior limb of the internal capsule was a potent predictor of severe (sensitivity, 92%; specificity, 80%; area under the curve (AUC), 0.91) and mild or severe (AUC, 0.75) developmental impairment. T2 relaxation time in the posterior limb of the internal capsule was a significant predictor of severe impairment (AUC, 0.76), whereas the brain parenchymal volume was a significant predictor of severe (AUC, 0.72) and mild or severe impairment (AUC, 0.71) outperforming the reported qualitative MRI scores (AUC, 0.66). CONCLUSION: The proposed cutoff values for T1 relaxation time in the posterior limb of the internal capsule and for total brain volume measurements, derived from synthetic MRI, show promise as predictors of both mild and severe neurodevelopmental impairment in very preterm infants.

Vulnerability of the Neonatal Connectome following Postnatal Stress.

Stress following preterm birth can disrupt the emerging foundation of the neonatal brain. The current study examined how structural brain development is affected by a stressful early environment and whether changes in topological architecture at term-equivalent age could explain the increased vulnerability for behavioral symptoms during early childhood. Longitudinal changes in structural brain connectivity were quantified using diffusion-weighted imaging (DWI) and tractography in preterm born infants (gestational age <28 weeks), imaged at 30 and/or 40 weeks of gestation (N = 145, 43.5% female). A global index of postnatal stress was determined based on the number of invasive procedures during hospitalization (e.g., heel lance). Higher stress levels impaired structural connectivity growth in a subnetwork of 48 connections (p = 0.003), including the amygdala, insula, hippocampus, and posterior cingulate cortex. Findings were replicated in an independent validation sample (N = 123, 39.8% female, n = 91 with follow-up). Classifying infants into vulnerable and resilient based on having more or less internalizing symptoms at two to five years of age (n = 71) revealed lower connectivity in the hippocampus and amygdala for vulnerable relative to resilient infants (p < 0.001). Our findings suggest that higher stress exposure during hospital admission is associated with slower growth of structural connectivity. The preservation of global connectivity of the amygdala and hippocampus might reflect a stress-buffering or resilience-enhancing factor against a stressful early environment and early-childhood internalizing symptoms.SIGNIFICANCE STATEMENT The preterm brain is exposed to various external stimuli following birth. The effects of early chronic stress on neonatal brain networks and the remarkable degree of resilience are not well understood. The current study aims to provide an increased understanding of the impact of postnatal stress on third-trimester brain development and describe the topological architecture of a resilient brain. We observed a sparser neonatal brain network in infants exposed to higher postnatal stress. Limbic regulatory regions, including the hippocampus and amygdala, may play a key role as crucial convergence sites of protective factors. Understanding how stress-induced alterations in early brain development might lead to brain (re)organization may provide essential insights into resilient functioning.

Additional Value of 3-Month Cranial Magnetic Resonance Imaging in Infants with Neonatal Encephalopathy following Perinatal Asphyxia.

OBJECTIVE: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia. METHODS: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy. RESULTS: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59. CONCLUSIONS: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.

From computer to bedside, involving neonatologists in artificial intelligence models for neonatal medicine.

In recent years, data have become the main driver of medical innovation. With increased availability and decreased price of storage and computing power, the potential for improvement in care is enormous. Many data-driven explorations have started. However, the actual implementation of artificial intelligence in healthcare remains scarce. We describe essential elements during a computer-to-bedside process in a data science project that support the crucial role of the neonatologist. IMPACT: There is a great potential for data science in neonatal medicine. Multidisciplinary teams form the foundation of a data science project. Domain experts will need to play a pivotal role. We need an open learning environment.

Brain injury and long-term outcome after neonatal surgery for non-cardiac congenital anomalies.

BACKGROUND: There is growing evidence that neonatal surgery for non-cardiac congenital anomalies (NCCAs) in the neonatal period adversely affects long-term neurodevelopmental outcome. However, less is known about acquired brain injury after surgery for NCCA and abnormal brain maturation leading to these impairments. METHODS: A systematic search was performed in PubMed, Embase, and The Cochrane Library on May 6, 2022 on brain injury and maturation abnormalities seen on magnetic resonance imaging (MRI) and its associations with neurodevelopment in neonates undergoing NCCA surgery the first month postpartum. Rayyan was used for article screening and ROBINS-I for risk of bias assessment. Data on the studies, infants, surgery, MRI, and outcome were extracted. RESULTS: Three eligible studies were included, reporting 197 infants. Brain injury was found in n = 120 (50%) patients after NCCA surgery. Sixty (30%) were diagnosed with white matter injury. Cortical folding was delayed in the majority of cases. Brain injury and delayed brain maturation was associated with a decrease in neurodevelopmental outcome at 2 years of age. CONCLUSIONS: Surgery for NCCA was associated with high risk of brain injury and delay in maturation leading to delay in neurocognitive and motor development. However, more research is recommended for strong conclusions in this group of patients. IMPACT: Brain injury was found in 50% of neonates who underwent NCCA surgery. NCCA surgery is associated with a delay in cortical folding. There is an important research gap regarding perioperative brain injury and NCCA surgery.

Early predictors of neurodevelopment after perinatal arterial ischemic stroke: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Perinatal arterial ischemic stroke (PAIS) often has lifelong neurodevelopmental consequences. We aimed to review early predictors (<4 months of age) of long-term outcome. METHODS: We carried out a systematic literature search (PubMed and Embase), and included articles describing term-born infants with PAIS that underwent a diagnostic procedure within four months of age, and had any reported outcome parameter ≥12 months of age. Two independent reviewers included studies and performed risk of bias analysis. RESULTS: We included 41 articles reporting on 1395 infants, whereof 1255 (90%) infants underwent follow-up at a median of 4 years. A meta-analysis was performed for the development of cerebral palsy (n = 23 studies); the best predictor was the qualitative or quantitative assessment of the corticospinal tracts on MRI, followed by standardized motor assessments. For long-term cognitive functioning, bedside techniques including (a)EEG and NIRS might be valuable. Injury to the optic radiation on DTI correctly predicted visual field defects. No predictors could be identified for behavior, language, and post-neonatal epilepsy. CONCLUSION: Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS. Future research should be focused on improving outcome prediction for non-motor outcomes. IMPACT: We present a systematic review of early predictors for various long-term outcome categories after perinatal arterial ischemic stroke (PAIS), including a meta-analysis for the outcome unilateral spastic cerebral palsy. Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS, while bedside techniques such as (a)EEG and NIRS might improve cognitive outcome prediction. Future research should be focused on improving outcome prediction for non-motor outcomes.

Neurodevelopmental consequences of preterm punctate white matter lesions: a systematic review.

OBJECTIVES: To evaluate punctate white matter lesion (PWML) influence in preterm infants on the long-term neurodevelopmental outcome (NDO). METHODS: PubMed and EMBASE were searched from January 1, 2000, to May 31, 2021. Studies were included in which PWML in preterm infants on MRI around term-equivalent age (TEA) and NDO at ≥12 months were reported. Study and patient characteristics and NDO on motor, cognitive, and behavioral domains were extracted. The quality of studies was assessed using the Cochrane-approved Quality in Prognosis Studies tool. RESULTS: This analysis included nine studies with a total of 1655 patients. Mean incidence of isolated PWML was 22.1%. All studies showed a relationship between PWML and motor delay. Two studies found a significant correlation between cognitive and behavioral outcomes and PWML. Number and PWML location are related to severity and impairment types. LIMITATIONS: PWML were not always separately described from generalized WMI, only studies with imaging around TEA were included, and studies were heterogenic in design and quality. CONCLUSIONS: PWML is common in preterm infants and predictive of adverse NDO, in particular on motor outcomes and less on cognitive and behavioral outcomes. The type and severity of impairments are related to the number and location of PMWL. IMPACT: PWML is common in preterm infants and seems predictive of adverse NDO. DWI and SWI MRI sequences are informative because the different patterns suggest a difference in the underlying pathology. The type and severity of impairments are related to the number and location of PMWL. Our review can inform clinicians and parents about the NDO of preterm infants with a diagnosis of PWML. Prospective neuroimaging case-control cohort studies are recommended.

The influence of nutrition on white matter development in preterm infants: a scoping review.

White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.

Susceptibility weighted imaging can be a sensitive sequence to detect brain damage in neonates with kernicterus: a case report.

BACKGROUND: Kernicterus in the acute phase is difficult to diagnose. It depends on a high signal on T1 at the globus pallidum and subthalamic nucleus level. Unfortunately, these areas also show a relatively high signal on T1 in neonates as an expression of early myelination. Therefore, a less myelin-dependent sequence, like SWI, may be more sensitive to detecting damage in the globus pallidum area. CASE PRESENTATION: A term baby developed jaundice on day three following an uncomplicated pregnancy and delivery. Total bilirubin peaked at 542 µmol/L on day four. Phototherapy was started, and an exchange transfusion was performed. ABR showed absent responses on day 10. MRI on day eight demonstrated abnormal high signal globus pallidus on T1w, isointense on T2w, without diffusion restriction, and high signal on SWI at globus pallidal and subthalamus level and phase image at globus pallidal level. These findings were consistent with the challenging diagnosis of kernicterus. On follow-up, the infant presented with sensorineural hearing loss and had a work-up for cochlear implant surgery. At 3 months of age, the follow-up MR shows normalization of the T1 and SWI signals and a high signal on T2. CONCLUSIONS: SWI seems more sensitive to injury than the T1w and lacks the disadvantage of the T1w sequence, where early myelin confers a high signal.

Morphine exposure and neurodevelopmental outcome in infants born extremely preterm.

AIM: To investigate the association between morphine exposure in the neonatal period and neurodevelopment at 2 and 5 years of age while controlling for potential confounders. METHOD: We performed a retrospective, single-centre cohort study on 106 infants (60 males, 46 females; mean gestational age 26 weeks [SD 1]) born extremely preterm (gestational age < 28 weeks). Morphine administration was expressed as cumulative dose (mg/kg) until term-equivalent age. Neurodevelopmental outcome was assessed at 2 years with the Bayley Scales of Infant and Toddler Development, Third Edition, Dutch version and at 5 years with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Dutch version. Multiple linear regression analysis was used to assess the association between morphine exposure and outcome. RESULTS: Sixty-four out of 106 (60.4%) infants included in the study received morphine. Morphine exposure was not associated with poorer motor, cognitive, and language subscores of the Bayley Scales of Infant and Toddler Development, Third Edition, Dutch version at 2 years. Morphine exposure was associated with lower Full-Scale IQ scores (p = 0.008, B = -9.3, 95% confidence interval [CI] = -15.6 to -3.1) and Performance IQ scores (p = 0.005, B = -17.5, 95% CI = -27.9 to -7) at 5 years of age. INTERPRETATION: Morphine exposure in infants born preterm is associated with poorer Full-Scale IQ and Performance IQ at 5 years. Individualized morphine administration is advised in infants born extremely preterm.

Self-reported quantity and quality of sleep in children and adolescents with a chronic condition compared to healthy controls.

To assess self-reported quantity and quality of sleep in Dutch children with a chronic condition compared to healthy controls and to the recommended hours of sleep for youth. Sleep quantity and quality were analyzed in children with a chronic condition (cystic fibrosis, chronic kidney disease, congenital heart disease, (auto-)immune disease, and medically unexplained symptoms (MUS); n = 291; 15 ± 3.1 years, 63% female. A subset of 171 children with a chronic condition were matched to healthy controls using Propensity Score matching, based on age and sex, ratio 1:4. Self-reported sleep quantity and quality were assessed with established questionnaires. Children with MUS were analyzed separately to distinguish between chronic conditions with and without an identified pathophysiological cause. Generally, children with a chronic condition met the recommended amount of sleep, however 22% reported poor sleep quality. No significant differences in sleep quantity and quality were found between the diagnosis groups. Children with a chronic condition and with MUS slept significantly more than healthy controls at ages 13, 15, and 16. Both at primary and secondary school, poor sleep quality was least frequent reported in children with a chronic condition and most often reported in children with MUS.  Conclusion: Overall, children with chronic conditions, including MUS, met the recommended hours of sleep for youth, and slept more than healthy controls. However, it is important to obtain a better understanding of why a substantial subset of children with chronic conditions, mostly children with MUS, still perceived their sleep quality as poor. What is Known: • According to the Consensus statement of the American Academy of Sleep medicine, typically developing children (6 to 12 years) should sleep 9 to 12 h per night, and adolescents (13 to 18 years) should sleep 8 to 10 h per night. • Literature on the optimal quantity and quality of sleep in children with a chronic condition is very limited. What is New: Our findings are important and provide novel insights: • In general, children with a chronic condition sleep according to the recommended hours of sleep. • A substantial subset of children with chronic conditions, perceived their sleep quality as poor. Although this was reported mostly by children with medically unexplained symptoms (MUS), the found poor sleep quality was independent of specific diagnosis.

Evaluation of Sleep Practices and Knowledge in Neonatal Healthcare.

BACKGROUND: Developmental care is designed to optimize early brain maturation by integrating procedures that support a healing environment. Protecting preterm sleep is important in developmental care. However, it is unclear to what extent healthcare professionals are aware of the importance of sleep and how sleep is currently implemented in the day-to-day care in the neonatal intensive care unit (NICU). PURPOSE: Identifying the current state of knowledge among healthcare professionals regarding neonatal sleep and how this is transferred to practice. METHODS: A survey was distributed among Dutch healthcare professionals. Three categories of data were sought, including (1) demographics of respondents; (2) questions relating to sleep practices; and (3) objective knowledge questions relating to sleep physiology and importance of sleep. Data were analyzed using Spearman's rho test and Cramer's V test. Furthermore, frequency tables and qualitative analyses were employed. RESULTS: The survey was completed by 427 participants from 34 hospitals in 25 Dutch cities. While healthcare professionals reported sleep to be especially important for neonates admitted in the NICU, low scores were achieved in the area of knowledge of sleep physiology. Most healthcare professionals (91.8%) adapted the timing of elective care procedures to sleep. However, sleep assessments were not based on scientific knowledge. Therefore, the difference between active sleep and wakefulness may often be wrongly assessed. Finally, sleep is rarely discussed between colleagues (27.4% regularly/always) and during rounds (7.5%-14.3% often/always). IMPLICATIONS: Knowledge about sleep physiology should be increased through education among neonatal healthcare professionals. Furthermore, sleep should be considered more often during rounds and handovers.

Respiratory Rate Extraction from Neonatal Near-Infrared Spectroscopy Signals.

Background: Near-infrared spectroscopy (NIRS) relative concentration signals contain 'noise' from physiological processes such as respiration and heart rate. Simultaneous assessment of NIRS and respiratory rate (RR) using a single sensor would facilitate a perfectly time-synced assessment of (cerebral) physiology. Our aim was to extract respiratory rate from cerebral NIRS intensity signals in neonates admitted to a neonatal intensive care unit (NICU). Methods: A novel algorithm, NRR (NIRS RR), is developed for extracting RR from NIRS signals recorded from critically ill neonates. In total, 19 measurements were recorded from ten neonates admitted to the NICU with a gestational age and birth weight of 38 ± 5 weeks and 3092 ± 990 g, respectively. We synchronously recorded NIRS and reference RR signals sampled at 100 Hz and 0.5 Hz, respectively. The performance of the NRR algorithm is assessed in terms of the agreement and linear correlation between the reference and extracted RRs, and it is compared statistically with that of two existing methods. Results: The NRR algorithm showed a mean error of 1.1 breaths per minute (BPM), a root mean square error of 3.8 BPM, and Bland-Altman limits of agreement of 6.7 BPM averaged over all measurements. In addition, a linear correlation of 84.5% (p < 0.01) was achieved between the reference and extracted RRs. The statistical analyses confirmed the significant (p < 0.05) outperformance of the NRR algorithm with respect to the existing methods. Conclusions: We showed the possibility of extracting RR from neonatal NIRS in an intensive care environment, which showed high correspondence with the reference RR recorded. Adding the NRR algorithm to a NIRS system provides the opportunity to record synchronously different physiological sources of information about cerebral perfusion and respiration by a single monitoring system. This allows for a concurrent integrated analysis of the impact of breathing (including apnea) on cerebral hemodynamics.

Ultra-Wideband Radar for Simultaneous and Unobtrusive Monitoring of Respiratory and Heart Rates in Early Childhood: A Deep Transfer Learning Approach.

Unobtrusive monitoring of children's heart rate (HR) and respiratory rate (RR) can be valuable for promoting the early detection of potential health issues, improving communication with healthcare providers and reducing unnecessary hospital visits. A promising solution for wireless vital sign monitoring is radar technology. This paper presents a novel approach for the simultaneous estimation of children's RR and HR utilizing ultra-wideband (UWB) radar using a deep transfer learning algorithm in a cohort of 55 children. The HR and RR are calculated by processing radar signals via spectrogram from time epochs of 10 s (25 sample length of hamming window with 90% overlap) and then transforming the resultant representation into 2-dimensional images. These images were fed into a pre-trained Visual Geometry Group-16 (VGG-16) model (trained on ImageNet dataset), with weights of five added layers fine-tuned using the proposed data. The prediction on the test data achieved a mean absolute error (MAE) of 7.3 beats per minute (BPM < 6.5% of average HR) and 2.63 breaths per minute (BPM < 7% of average RR). We also achieved a significant Pearson's correlation of 77% and 81% between true and extracted for HR and RR, respectively. HR and RR samples are extracted every 10 s.

The relationship between interhemispheric synchrony, morphine and microstructural development of the corpus callosum in extremely preterm infants.

The primary aim of this study is to examine whether bursting interhemispheric synchrony (bIHS) in the first week of life of infants born extremely preterm, is associated with microstructural development of the corpus callosum (CC) on term equivalent age magnetic resonance imaging scans. The secondary aim is to address the effects of analgesics such as morphine, on bIHS in extremely preterm infants. A total of 25 extremely preterm infants (gestational age [GA] < 28 weeks) were monitored with the continuous two-channel EEG during the first 72 h and after 1 week from birth. bIHS was analyzed using the activation synchrony index (ASI) algorithm. Microstructural development of the CC was assessed at ~ 30 and ~ 40 weeks of postmenstrual age (PMA) using fractional anisotropy (FA) measurements. Multivariable regression analyses were used to assess the primary and secondary aim. Analyses were adjusted for important clinical confounders: morphine, birth weight z-score, and white matter injury score. Due to the reduced sample size, only the most relevant variables, according to literature, were included. ASI was not significantly associated with FA of the CC at 30 weeks PMA and at 40 weeks PMA (p > .5). ASI was positively associated with the administration of morphine (p < .05). Early cortical synchrony may be affected by morphine and is not associated with the microstructural development of the CC. More studies are needed to evaluate the long-term effects of neonatal morphine treatment to optimize sedation in this high-risk population.