NAPping PAnts (NAPPA): An open wearable solution for monitoring Infant's sleeping rhythms, respiration and posture.

Study objectives: To develop a non-invasive and practical wearable method for long-term tracking of infants' sleep. Methods: An infant wearable, NAPping PAnts (NAPPA), was constructed by combining a diaper cover and a movement sensor (triaxial accelerometer and gyroscope), allowing either real-time data streaming to mobile devices or offline feature computation stored in the sensor memory. A sleep state classifier (wake, N1/REM, N2/N3) was trained and tested for NAPPA recordings (N = 16649 epochs of 30 s), using hypnograms from co-registered polysomnography (PSG) as a training target in 33 infants (age 2 weeks to 18 months; Mean = 4). User experience was assessed from an additional group of 16 parents. Results: Overnight NAPPA recordings were successfully performed in all infants. The sleep state classifier showed good overall accuracy (78 %; Range 74-83 %) when using a combination of five features related to movement and respiration. Sleep depth trends were generated from the classifier outputs to visualise sleep state fluctuations, which closely aligned with PSG-derived hypnograms in all infants. Consistently positive parental feedback affirmed the effectiveness of the NAPPA-design. Conclusions: NAPPA offers a practical and feasible method for out-of-hospital assessment of infants' sleep behaviour. It can directly support large-scale quantitative studies and development of new paradigms in scientific research and infant healthcare. Moreover, NAPPA provides accurate and informative computational measures for body positions, respiration rates, and activity levels, each with their respective clinical and behavioural value.

Microstructural White Matter Abnormalities in Children and Adolescents With Narcolepsy Type 1.

BACKGROUND: In 2010, the H1N1 Pandemrix vaccination campaign was followed by a sudden increase in narcolepsy type 1 (NT1). We investigated the brain white matter microstructure in children with onset of NT1 within two years after the Pandemrix vaccination. METHODS: We performed diffusion-weighted magnetic resonance imaging (MRI) on 19 children and adolescents with NT1 and 19 healthy controls. Imaging was performed at a median of 4 years after the diagnosis at a median age of 16 years. For the MRI, we used whole-brain tractography and tract-based spatial statistics (TBSS). We compared these results with medical records and questionnaire data. RESULTS: Narcoleptic children showed a global decrease in mean, axial, and radial diffusivity and an increase in planarity coefficient in the white matter TBSS skeleton and tractography. These differences were widespread, and there was an increased asymmetry of the mean diffusivity in children with NT1. The global microstructural metrics were reflected in behavior, and especially the axial diffusion levels correlated with anxiety and depression symptoms and social and behavioral problems. CONCLUSIONS: In pediatric patients with Pandemrix-associated NT1, several global changes in the brain white matter network skeleton were observed within five years after the onset of NT1. The degree of changes correlates with behavioral problems.

Type one chiari malformation as a cause of central sleep apnea and hypoventilation in children.

OBJECTIVES: Chiari type 1 malformation (CM1) may occasionally lead to central sleep apnea (CSA). We studied, in a large clinical cohort of pediatric CM1 patients, the effect of CM1 on breathing during sleep. METHODS: This is a retrospective single pediatric pulmonology center study with a systematic evaluation of pediatric CM1 patients under age 18 with polysomnography (PSG) during 2008-2020. Children with syndromes were excluded. All patients had undergone head and spine magnetic resonance imaging. RESULTS: We included 104 children with CM1 with a median age of 7 (interquartile range (IQR) 5-13) years. The median extent of tonsillar descent (TD) was 13 (IQR 10-18) mm. Syringomyelia was present in 19 children (18%). Of all children, 53 (51%) had normal PSG, 35 (34%) showed periodic breathing or central apnea and hypopnea index ≥5 h-1, and 16 (15%) displayed features of compensated central hypoventilation and end-tidal or transcutaneous carbon dioxide 99th percentile level above 50 mmHg. TD had the best predictive value for central breathing disorders. In a linear model, both age (61%) and TD (39%) predicted median breathing frequency (R = 0.33, p < 0.001). CONCLUSIONS: Although severe CSA is a rare complication of brainstem compression in pediatric patients with CM1, short arousal-triggered episodes of periodic breathing and mild compensated central hypoventilation are common. TD shows the best but still poor prediction of the presence of a central breathing disorder. This highlights the use of PSG in patient evaluation. Posterior fossa decompression surgery effectively treats central breathing disorders.

Children's interstitial lung disease: Multidetector computed tomography patterns and correlations between imaging and histopathology.

PURPOSE: Childhood interstitial lung disease (chILD) is an umbrella concept covering a wide range of rare lung diseases, many of which are unique to childhood. The diagnosis is based on clinical presentation, multidetector computed tomography (MDCT), genetic testing, lung-function testing, and lung biopsy. Because knowledge of the usefulness of MDCT pattern recognition in ChILD is at present limited, we examined the occurrence of MDCT patterns in children with histologically confirmed interstitial lung disease. METHOD: We searched the biopsy, MDCT, and clinical information database of a single national paediatric referral hospital for 2004-2020. Data were from affected children under age 18. MDCT images we reanalysed while blinded to the identity and referral information. RESULTS: We included 90 patients, of whom 63 (70 %) were male. The median age at biopsy was 1.3 years (interquartile range 0.1-16.8). Biopsy findings fell into 26 histological classes covering all nine chILD classification categories. We recognized six distinct MDCT patterns: neuroendocrine cell hyperplasia of infancy (23), organizing pneumonia (5), non-specific interstitial pneumonia (4), bronchiolitis obliterans (3), pulmonary alveolar proteinosis (2), and bronchopulmonary dysplasia (n = 2). Of the total 90, in 51 (57 %) children, none of these six MDCT patterns appeared. Of those 39 children with a recognizable MDCT pattern, in 34 (87 %), that pattern predicted their final diagnosis. CONCLUSIONS: Among cases of chILD, we identified a specific predefined MDCT pattern in only 43 %. However, when such a recognizable pattern occurred, it was predictive of the final chILD diagnosis.

Obstructive sleep apnea in young infants: Sleep position dependence and spontaneous improvement.

OBJECTIVES: The natural evolution of obstructive sleep apnea (OSA) in young infants is not established. METHODS: We re-evaluated 10-year pediatric sleep center infant polysomnography (PSG) data, excluding infants with syndromes, genetic defects, structural anomalies or periodic breathing > 5% of sleep time. RESULTS: Obstructive events > 1 h-1 were evident in 255 infants, of which 91 were eligible for the study. Of the 38 infants in a follow-up study, 30 (79%) were male, 15 (40%) were born prematurely, 25 (66%) had observed apneas, and 13 (33%) had experienced a brief, unexplained event or had a sibling of the infant died suddenly. The first PSG was performed at a median corrected age of 4 weeks (interquartile range [IQR] 2-7) and the second at 11 weeks (IQR 9-14). The obstructive apnea and hypopnea index (OAHI) was greater in the supine compared to side-sleeping position in both recordings (p < 0.001), whereas OAHI dropped from 10 h-1 (IQR 6-24) in the first PSG to 3 h-1 (IQR 1-9) in the second PSG (p < 0.001). OSA alleviation was also observable as a decrease in the number of oxygen desaturations (p < 0.001), as a decrease in transcutaneous (p = 0.001) and end-tidal carbon dioxide (p = 0.01) 95th percentile levels, and work of breathing (p = 0.002). Seven infants had a third PSG to verify a satisfactory improvement of OSA. CONCLUSIONS: OSA in young infants without a clear syndrome or structural anomaly is sleep position dependent and shows improvement during the following few months.

Sleep-related breathing disorder in non-infectious pulmonary complications after pediatric allogeneic stem cell transplantation.

BACKGROUND: Chronic lung problems are a rare but serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). We studied clinical phenotypes and polysomnography appearance of breathing abnormality in late onset non-infectious pulmonary complications (NIPS). METHODS: We reviewed Finnish national reference database between the years 1999 and 2016. We identified 12 children with most severely decreased pulmonary function and performed polysomnography and 24 aged-matched controls out of 325 performed pediatric allogeneic HSCTs. RESULTS: All patients with NIPS had severely decreased pulmonary function already at 6 months post HSCT with median FEV1 value 42% (interquartile range (IQR) 30-52%) of predicted normal values. Seven children had obstructive and five children more restrictive lung function. Children with obstructive lung function showed laborious breathing (7/7), decreased oxygenation and ventilation-to-perfusion mismatch (6/7), or REM-sleep-related hypoventilation (4/7) on polysomnography. Children with restrictive lung function (5/12) did not show sleep-related breathing disorder. CONCLUSIONS: Children going through allogeneic HSCT who develop severe chronic obstructive lung function are more likely to present with sleep-related hypoxia and hypoventilation than children with restrictive lung function. IMPACT: Children with severe obstructive lung function and chronic lung graft-versus-host disease following hematopoietic stem cell transplantation are more likely to present with sleep-related mild hypoxia and hypoventilation than children with restrictive lung disease. To our knowledge there are no reports on sleep-related breathing disorders and ventilatory function measured by polysomnography in children with pulmonary complications after allogeneic HSCT. Polysomnography may add to the differential diagnostics between patients with BOS and other non-infectious pulmonary complications.

Obstructive sleep apnea is position dependent in young infants.

BACKGROUND: Obstructive sleep apnea in infants with Pierre Robin sequence is sleep-position dependent. The influence of sleep position on obstructive events is not established in other infants. METHODS: We re-evaluated ten-year pediatric sleep center data in infants aged less than six months, with polysomnography performed in different sleep positions. We excluded infants with syndromes, genetic defects, or structural anomalies. RESULTS: Comparison of breathing between supine and side sleeping positions was performed for 72 infants at the median corrected age of 4 weeks (interquartile range (IQR) 2-8 weeks). Of the infants, 74% were male, 35% were born prematurely, and 35% underwent study because of a life-threatening event or for being a SIDS sibling. Upper airway obstruction was more frequent (obstructive apnea-hypopnea index (OAHI), p < 0.001), 95th-percentile end-tidal carbon dioxide levels were higher (p = 0.004), and the work of breathing was heavier (p = 0.002) in the supine than in the side position. Median OAHI in the supine position was 8 h-1 (IQR 4-20 h-1), and in the side position was 4 h-1 (IQR 0-10 h-1). CONCLUSIONS: Obstructive upper airway events in young infants are more frequent when supine than when sleeping on the side. IMPACT: The effect of sleep position on obstructive sleep apnea is not well established in infants other than in those with Pierre Robin sequence. A tendency for upper airway obstruction is position dependent in most infants aged less than 6 months. Upper airway obstruction is more common, end-tidal carbon dioxide 95th-percentile values higher, and breathing more laborious in the supine than in the side-sleeping position. Upper airway obstruction and obstructive events have high REM sleep predominance. As part of obstructive sleep apnea treatment in young infants, side-sleeping positioning may prove useful.

Supplemental Oxygen Treats Periodic Breathing without Effects on Sleep in Late-Preterm Infants.

BACKGROUND: The effect of supplemental oxygen on sleep has not been studied in preterm infants. METHODS: We studied 18 stable late-preterm infants with observed periodic breathing at a median gestational age of 36 weeks. Polysomnography was performed on room air and on 25% oxygen-enriched ambient air. RESULTS: Supplemental oxygen did not affect sleep stage distribution, sleep efficiency, the frequency of sleep stage transitions, the appearance of rapid-eye movement (REM) sleep periods, or the high number of spontaneous arousals. The percentage in periodic breathing out of total sleep time decreased from 10% (interquartile range [IQR] 5-9%) on room air to 1% (IQR 0-3%) (p < 0.001) on supplemental oxygen. Also, the number of central apneas decreased from 48 (IQR 32-68) to 23 (IRQ 15-32) per hour (p < 0.001), and the number of oxygen desaturations of a minimum 3% from 38 (IQR 29-74) to 10 (IQR 5-24) per hour (p < 0.001). On room air in non-REM sleep, the median end-tidal carbon dioxide values were systematically lower during periodic breathing at 5.1 (IQR 4.6-6.4) kPa than during stable breathing at 5.5 (4.9-5.9) kPa (p < 0.0001). CONCLUSIONS: In late-preterm infants, supplemental oxygen effectively reduces periodic breathing and the number of oxygen desaturations while having no significant effect on sleep. The results support the importance of carotid body over-reactivity on the genesis of periodic breathing in preterm infants.

Caffeine is a respiratory stimulant without effect on sleep in the short-term in late-preterm infants.

BACKGROUND: Caffeine is widely used in preterm infants for apnea control. It has no effect on sleep in the only existing polysomnographic study including ten preterm infants Behavioral and polygraphic studies have conflicting results. METHODS: We studied 21 late-preterm infants at a median gestational age of 36 weeks. Polysomnography was performed twice, at baseline on day 1 and on the day after the onset of caffeine treatment (20 mg/kg loading and 5 mg/kg morning maintenance dose). RESULTS: Caffeine acted short term as a breathing stimulant with reduction of apneas, improved baseline SpO2 (p < 0.001), and decreased 95 percentile of end-tidal carbon dioxide level (p < 0.01). It also increased arousal frequency to SpO2 desaturations of more than 5% (p < 0.001). Caffeine did not affect sleep stage distribution, sleep efficiency, frequency of sleep stage transitions, appearance of REM periods, or the high number of spontaneous arousals. The median spontaneous arousal count was 18 per hour at baseline, and 16 per hour during caffeine treatment (p = 0.88). CONCLUSIONS: In late-preterm infants, caffeine has a clear short-term respiratory stimulant effect, and it increases the arousal frequency to hypoxia. However, caffeine does not appear to act as a central nervous system stimulant, and it has no acute effect on sleep quality. IMPACT: Effects of caffeine on sleep in preterm infants has previously been investigated with only one full polysomnographic study including ten preterm infants. The study showed no effect. The current study shows that caffeine acts short term as a respiratory stimulant and increases arousal frequency to hypoxia. Although a potent central nervous system (CNS) stimulant in adults, caffeine does not seem to have similar acute CNS effect in late-preterm infants. The onset of caffeine treatment has no short-term effect on sleep stage distribution, sleep efficiency, frequency of sleep stage transitions, appearance of REM periods, or the high number of spontaneous arousals.

Finnish children who experienced narcolepsy after receiving the Pandemrix vaccine during the 2009-2010 H1N1 pandemic demonstrated high level of psychosocial problems.

AIM: We assessed psychosocial burdens in children who developed narcolepsy after receiving the Pandemrix H1N1 vaccine during the 2009-2010 pandemic. Parental quality of life was also assessed. METHODS: This multicentre study covered four of the five Finnish University Hospital Districts, which dealt with about 90% of the paediatric narcolepsy cases after the Pandemrix vaccination. The medical records of children diagnosed from 2010 to 2014 were reviewed. The questionnaires included the Youth Self-Report (YSR), Children's Depression Inventory (CDI), the Child Behaviour Checklist (CBCL) and questions on parental resources, stress and quality of life. RESULTS: We obtained the medical records of 94 children who were aged 5-17 years at the time of their narcolepsy diagnosis and questionnaire data for 73 of those children. Most children had strong narcolepsy symptoms, and 25% had CDI scores that suggested depression. In addition, 41% had total CBCL problem scores above the clinically significant limit and 48% were anxious, withdrawn and had somatic complaints. Sleep latency was weakly associated with the CBCL total problem score. Half of the children needed psychiatric interventions and parental stress was common. CONCLUSION: Depression and behavioural problems were common in children with narcolepsy after the Pandemrix vaccination and their parents frequently reported feeling stressed.

Pierre Robin sequence causes position-dependent obstructive sleep apnoea in infants.

INTRODUCTION: Obstructive sleep apnoea (OSA) and feeding difficulties are key problems for Pierre Robin sequence (PRS) infants. OSA management varies between treatment centres. Sleep positioning represents the traditional OSA treatment, although its effectiveness remains insufficiently evaluated. DESIGN: To complete a polysomnographic (PSG) evaluation of effect of sleep position on OSA in PRS infants less than 3 months of age. We analysed a 10-year national reference centre dataset of 76 PRS infants. PSG was performed as daytime recordings for 67 in the supine, side and prone sleeping position when possible. In most cases, recording included one cycle of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in each position. RESULTS: One-third of infants (9/76, 12%) had severe OSA needing treatment intervention prior to PSG. During PSG, OSA with an obstructive apnoea and hypopnoea index (OAHI) >5 per hour was noted in 82% (55/67) of infants. OSA was most severe in the supine and mildest in the side or in the prone positions. The median OAHI in the supine, side and prone positions were 31, 16 and 19 per hour of sleep (p=0.003). For 68% (52/67) of the infants, either no treatment or positional treatment alone was considered sufficient. CONCLUSIONS: The incidence of OSA was 84% (64/76) including the nine infants with severe OSA diagnosed prior to PSG. For the most infants, the OSA was sleep position dependent. Our study results support the use of PSG in the evaluation of OSA and the use of sleep positioning as a part of OSA treatment.

Spontaneous and apnea arousals from sleep in preterm infants.

BACKGROUND: The significance of arousal in apnea termination in preterm infants is not known. METHODS: We investigated the appearance of arousals from sleep with polysomnography for 21 preterm infants at a median age of 36 gestational weeks. RESULTS: The polysomnographic appearance of sleep was fragmented by frequent arousals. The number of spontaneous arousals unrelated to apneas was 18 per hour in sleep; higher in rapid eye movement (REM) sleep than in non-REM sleep (p < 0.001). Eighty-two percent of arousals were regarded as spontaneous, and 18% were related to apneas. In turn, arousal followed 5% of all apneas; 30% of mixed, 2% of central, and 20% of long apneas defined as apnea of prematurity. Apneas without an arousal led to lower oxygen saturation levels than those followed by an arousal (p < 0.001). Mixed apneas with an arousal had stronger breathing effort and a higher number of breaths compared with apneas without an arousal (p < 0.05). CONCLUSIONS: In preterm infants, frequent spontaneous arousals or arousal-type phenomena make the polysomnographic appearance of sleep fragmented. However, even long apneas or hypoxia commonly fail to elicit arousals or any sign of sleep interruption. Our findings suggest that arousal appears not to be the main mechanism for apnea termination in preterm infants. IMPACT: Polysomnographic appearance of sleep in preterm infants is fragmented by arousals. Contrary to older children and adults, arousal to apnea is uncommon in preterm infants. Even long mixed apneas with desaturation mostly fail to elicit an arousal response. In preterm infants, apnea termination appears not to depend on an arousal. Low arousability is suggested to be caused by a low ventilation response to hypoxia.

An Open Source Classifier for Bed Mattress Signal in Infant Sleep Monitoring.

OBJECTIVE: To develop a non-invasive and clinically practical method for a long-term monitoring of infant sleep cycling in the intensive care unit. METHODS: Forty three infant polysomnography recordings were performed at 1-18 weeks of age, including a piezo element bed mattress sensor to record respiratory and gross-body movements. The hypnogram scored from polysomnography signals was used as the ground truth in training sleep classifiers based on 20,022 epochs of movement and/or electrocardiography signals. Three classifier designs were evaluated in the detection of deep sleep (N3 state): support vector machine (SVM), Long Short-Term Memory neural network, and convolutional neural network (CNN). RESULTS: Deep sleep was accurately identified from other states with all classifier variants. The SVM classifier based on a combination of movement and electrocardiography features had the highest performance (AUC 97.6%). A SVM classifier based on only movement features had comparable accuracy (AUC 95.0%). The feature-independent CNN resulted in roughly comparable accuracy (AUC 93.3%). CONCLUSION: Automated non-invasive tracking of sleep state cycling is technically feasible using measurements from a piezo element situated under a bed mattress. SIGNIFICANCE: An open source infant deep sleep detector of this kind allows quantitative, continuous bedside assessment of infant's sleep cycling.

Caffeine and supplemental oxygen effectively suppress periodic breathing with only minor effects during long episodes of apnoea in preterm infants.

AIM: We investigated the characteristics and effects of sleep stage, supplemental oxygen and caffeine on periodic breathing (PB) and apnoea of prematurity (AOP) in preterm infants. METHODS: This 2013-2015 study recruited 21 preterm infants on neonatal wards in the Helsinki and Uusimaa Hospital District, Finland, at a median corrected gestational age of 35.7 weeks and performed polysomnography at baseline, during supplemental oxygen and during caffeine treatment. RESULTS: All infants demonstrated PB, during a median of 11% of sleep time and 85% of PB occurred during non-rapid eye movement sleep (NREM). Apnoea episodes were brief during PB, but 66% were associated with oxygen desaturation. Supplemental oxygen substantially reduced PB time by 99% and caffeine by 91%. Oxygen desaturation decreased from 38 per hour at baseline to 8.5 with oxygen and 24 with caffeine (all p < 0.001). AOPs decreased from 1.4 per hour at baseline to 0.4 with oxygen (p = 0.03) and 0.3 with caffeine (p = 0.07). Most (84%) apnoea episodes over 15 seconds were mixed episodes during REM sleep. CONCLUSION: PB occurred predominantly during NREM sleep, caused intermittent hypoxia, and was suppressed by supplemental oxygen and caffeine. In contrast, long apnoea episodes representing AOP were only modestly decreased.

Maternal asthma is associated with increased risk of perinatal mortality.

BACKGROUND: Asthma is the most common chronic disease during pregnancy and it may have influence on pregnancy outcome. OBJECTIVES: Our goal was to assess the association between maternal asthma and the perinatal risks as well as possible effects of asthma medication. METHODS: The study was based on a nationwide Finnish register-based cohort between the years 1996 and 2012 in the Drug and Pregnancy Database. The register data comprised 962 405 singleton live and stillbirths, 898 333 (93.3%) pregnancies in mothers with neither confirmed asthma nor use of asthma medication (controls), and 26 674 (2.8%) pregnancies with confirmed maternal asthma. 71% of mothers with asthma used asthma medication. The diagnosis of asthma was based on the mothers' right for subsidised medication which is carefully evaluated by strict criteria including pulmonary function testing. Odds ratio was used in comparison. Premature birth (PB), low birth weight, small for gestational age (SGA), neonatal death were the main outcome measures. RESULTS: Maternal asthma was associated with adjusted odds ratios (aORs) for perinatal mortality 1.24 (95% CI 1.05 to 1.46), preterm birth 1.18 (1.11 to 1.25), low birth weight 1.29 (1.21 to 1.37), fetal growth restriction (SGA) 1.32, (1.24 to 1.40), and asphyxia 1.09 (1.02 to 1.17). Asthma treatment reduced the increased risk of preterm birth aOR 0.85 (95% CI 0.76 to 0.96) but mothers with treated asthma had higher risks of fetal growth restriction (SGA) aOR 1.26 (1.10 to 1.45), and asphyxia aOR 1.37 (1.17 to 1.61) than mothers with untreated asthma. CONCLUSION: Asthma is associated with increased risks of perinatal mortality, preterm birth, low birth weight, fetal growth restriction (SGA), and asphyxia. Asthma treatment reduces the risk of preterm delivery, but it does not seem to reduce other complications such as perinatal mortality.

Local changes in computational non-rapid eye movement sleep depth in infants.

OBJECTIVE: Deep NREM sleep and its hallmark EEG phenomenon slow wave activity (SWA) are under homeostatic control in adults. SWA is also locally regulated as it increases in the brain areas that have been used intensively. Moreover, in children, SWA is a marker of cortical maturation. In the present study the local properties of NREM sleep depth were evaluated using the quantitative mean frequency method. We aimed to study if age is related to NREM sleep depth in young infants. In addition, we studied if young infants have local differences in their NREM sleep. METHODS: Ambulatory over-night polysomnographies were recorded in 59 healthy and full-term infants at the age of one month. The infants were divided into two age groups (<44 weeks and ≥44 weeks) to allow maturational evaluations. RESULTS: The quantitative sleep depth analysis showed differences between the age groups. In addition, there were local sleep depth differences within the age groups. CONCLUSIONS: The sleep depth change with age is most likely related to cortical maturation, whereas the local sleep depth gradients might also reflect the use-dependent properties of SWA. SIGNIFICANCE: The results support the idea that young infants have frontal cortical processing.