Michael S. Urschitz

Habitual snoring, intermittent hypoxia, and impaired behavior in primary school children.

Objectives. Sleep-disordered breathing is associated with impaired behavior and poor academic performance in children. We aimed to determine the extent of behavioral problems in snoring children, clarify the role of intermittent hypoxia, and test the reversibility of impaired behavior and poor academic performance. Methods. In 1144 children, habitual snoring (HS; snoring frequently or always) and impaired behavior were assessed using parental questionnaires. Intermittent hypoxia (ie, presence of ≥5 arterial oxygen desaturations by ≥4% or ≥1 desaturation to ≤90%) was investigated with pulse oximetry. Poor academic performance (grade 4–6 on a 6-point scale in mathematics, science, or spelling) was based on the last school report. HS, impaired behavior, and academic performance were reevaluated after 1 year. Adjusted odds ratios (ORs) were calculated using unconditional logistic regression. Results. HS was significantly associated with hyperactive (OR: 2.4) and inattentive behavior (OR: 4.0), daytime tiredness (OR: 7.1), and sleepiness (OR: 2.6–4.8). These associations were independent of intermittent hypoxia. HS was also significantly associated with bad conduct (OR: 2.8), emotional symptoms (OR: 5.5), and peer problems (OR: 9.7). At follow-up, hyperactive and inattentive behavior but not academic success had significantly improved in children in whom HS had ceased. Conclusions. We suggest that impaired behavior is a key feature of HS independent of intermittent hypoxia and improves when HS ceases.

Reference Values for Nocturnal Home Polysomnography in Primary Schoolchildren

Abbreviated home polysomnography may be an alternative to laboratory polysomnography in children but is not yet generally accepted, partly due to a lack of reference values. Also, there are no normative data on respiratory events obtained using nasal prongs. We determined the prevalence and frequency of central, obstructive, and mixed apneas and hypopneas in a population-based sample of 50 children (mean age 10.1 years) using abbreviated home polysomnography and nasal prongs. We also determined the frequency of movements/arousals and body position changes. All children had central apneas. Obstructive apneas, mixed apneas, and hypopneas were found in 36%, 6%, and 14% of children, respectively. Average number of central, obstructive, and mixed apneas; hypopneas; movement/arousals; and body position changes per hour of sleep was 1.5, 0.1, 0.01, 0.02, 8.2, and 3.7, respectively. The corresponding cutoff values (mean plus 2 standard deviations or 95th centile) were 3.7, 0.7, 0.1, 0.2, 13.4, and 9.1, respectively. We did not find significant gender differences regarding any sleep variable under study. The presented reference values may help clinicians and researchers to improve the interpretation of abbreviated home polysomnography in school-age children.

Nocturnal Arterial Oxygen Saturation and Academic Performance in a Community Sample of Children

Objective. Hypoxemia, often assessed via pulse oximetry, is associated with neurocognitive deficits in children. The best way to qualify hypoxemia, or which level of hypoxemia already affects cognition, is unknown. Methods. We assessed the association of pulse oximetry-derived variables that qualify hypoxemia with impaired academic performance in mathematics in a population-based cross-section of 995 primary school children who underwent overnight home recordings of motion-resistant new-generation pulse oximeter saturation (Spo2). Impaired academic performance in mathematics was based on the last school report and defined as grade 4 to 6 on a 6-point scale (ie, approximately the lowest quintile grades). Results. Of 10 variables under study, only the nadir of the Spo2 values was significantly associated with impaired performance. Categories of this variable representing mild (ie, 91%–93% Spo2; odds ratio: 1.65; 95% confidence interval: 1.06–2.56) and moderate hypoxemia (ie, ≤90% Spo2; odds ratio: 2.28; 95% confidence interval: 1.30–4.01) both were associated with impaired performance in mathematics. Conclusions. We suggest using the nadir of the Spo2 values in an overnight study to qualify hypoxemia in future studies. This variable may predict neurocognitive deficits in school children. Mild hypoxemia, as yet widely considered benign, may already affect cognition in childhood.

Randomised crossover trial of four nasal respiratory support systems for apnoea of prematurity in very low birthweight infants.

Background: Apnoea of prematurity (AOP) is a common problem in preterm infants which can be treated with various modes of nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV). It is not known which mode of NCPAP or NIPPV is most effective for AOP. Objective: To assess the effect of four NCPAP/NIPPV systems on the rate of bradycardias and desaturation events in very low birthweight infants. Methods: Sixteen infants (mean gestational age at time of study 31 weeks, 10 males) with AOP were enrolled in a randomised controlled trial with a crossover design. The infants were allocated to receive nasal pressure support using four different modes for 6 h each: NIPPV via a conventional ventilator, NIPPV and NCPAP via a variable flow device, and NCPAP delivered via a constant flow underwater bubble system. The primary outcome was the cumulative event rate of bradycardias (⩽80 beats per minute) and desaturation events (⩽80% arterial oxygen saturation), which was obtained from cardio-respiratory recordings. Results: The median event rate was 6.7 per hour with the conventional ventilator in NIPPV mode, and 2.8 and 4.4 per hour with the variable flow device in NCPAP and NIPPV mode, respectively (p value<0.03 for both compared to NIPPV/conventional ventilator). There was no significant difference between the NIPPV/conventional ventilator and the underwater bubble system. Conclusion: A variable flow NCPAP device may be more effective in treating AOP in preterm infants than a conventional ventilator in NIPPV mode. It remains unclear whether synchronised NIPPV would be even more effective.

Sleep problems and daytime somnolence in a German population‐based sample of snoring school‐aged children

Habitual snoring is associated with daytime symptoms like tiredness and behavioral problems. Its association with sleep problems is unclear. We aimed to assess associations between habitual snoring and sleep problems in primary school children. The design was a population‐based cross‐sectional study with a nested cohort study. The setting was twenty‐seven primary schools in the city of Hannover, Germany. Habitual snoring and sleep problems were assessed in primary school children using an extended version of Gozals sleep‐disordered breathing questionnaire (n = 1144). Approximately 1 year later, parents of children reported to snore habitually (n = 114) and an equal number of children who snored never or occasionally were given the Sleep Disturbance Scale for Children, a validated questionnaire for the assessment of pediatric sleep problems. Snoring status was re‐assessed using the initial questionnaire and children were then classified as long‐term habitual snorers or ex‐habitual snorers. An increasing prevalence of sleep problems was found with increasing snoring frequency for sleep‐onset delay, night awakenings, and nightmares. Long‐term habitual snorers were at significantly increased risk for sleep–wake transition disorders (e.g. rhythmic movements, hypnic jerks, sleeptalking, bruxism; odds ratio, 95% confidence interval: 12.0, 3.8–37.3), sleep hyperhidrosis (3.6, 1.2–10.8), disorders of arousal/nightmares (e.g. sleepwalking, sleep terrors, nightmares; 4.6, 1.3–15.6), and excessive somnolence (i.e. difficulty waking up, morning tiredness, daytime somnolence; 6.3, 2.2–17.8). Ex‐habitual snorers were at increased risk for sleep–wake transition disorders (4.4, 1.4–14.2). Habitual snoring was associated with several sleep problems in our study. Long‐term habitual snorers were more likely to have sleep problems than children who had stopped snoring spontaneously.

An Oral Appliance With Velar Extension for Treatment of Obstructive Sleep Apnea in Infants With Pierre Robin Sequence

Objective A new oral appliance to treat obstructive sleep apnea in infants with Pierre Robin sequence has recently been shown to be superior to a sham procedure. We now investigate safety and long-term effects of this appliance on obstructive sleep apnea in infants with Pierre Robin sequence. Design Case series with repetitive follow-up examinations. Setting Tertiary neonatal intensive care unit at the University Childrens Hospital Tuebingen, Germany. Patients Fifteen infants (11 girls and four boys; median age, 5 days) with Pierre Robin sequence and obstructive sleep apnea (i.e., mixed-obstructive-apnea index > 3). Intervention A custom-made intraoral appliance with velar extension was used continuously in situ from admission until 3 months after hospital discharge. Main Outcome Measure The mixed-obstructive-apnea index was determined prior to the intervention at admission, at discharge, and 3 months later using polygraphic sleep studies. The geometric mean of the mixed-obstructive-apnea index and its 95% confidence interval were calculated. Results Compared with admission (mean, 17.2; 95% confidence interval, 11.1–26.7), there was a significant decrease in the mixed-obstructive-apnea index to discharge (mean, 3.8; 95% confidence interval, 2.2–6.6) and 3 months later (mean, 1.2; 95% confidence interval, 0.7–2.2; p value < .001). No severe adverse events occurred. Conclusions This oral appliance was safe and appears to treat obstructive sleep apnea effectively in infants with Pierre Robin sequence.

Using Time-Oriented Data Abstraction Methods to Optimize Oxygen Supply for Neonates

Therapy management needs sophisticated patient monitoring and therapy planning, especially in high-frequency domains, like Neonatal Intensive Care Units (NICUs), where complex data sets are collected every second. An elegant method to tackle this problem is the use of time-oriented, skeletal plans. Asgaard is a framework for the representation, visualization, and execution of such plans. These plans work on qualitative abstracted time-oriented data which closely resemble the concepts used by experienced clinicians.This papers presents the data abstraction unit of the Asgaard system. It provides a range of connectable data abstraction methods bridging the gap between the raw data collected by monitoring devices and the abstract concepts used in therapeutic plans. The usability of this data abstraction unit is demonstrated by the implementation of a controller for the automated optimization of the fraction of inspired oxygen (FiO2). The use of the time-oriented data abstraction methods results in safe and smooth adjustment actions of our controller in a neonatal care setting.

Position dependent changes of cerebral blood flow velocities in premature infants.

Abstract. The supine or prone positioning of infants has been a cause of much controversy. Recently it has been postulated that the position dependent hypoperfusion of the brainstem represents a possible cause of sudden infant death. To demonstrate position dependency and maturational changes of cerebral perfusion in premature newborn infants we investigated cerebral blood flow velocities (CBFV) in the main supratentorial and brainstem cerebral arteries. Measurements of CBFV were done with transfontanellar colour-coded Doppler sonography in the internal carotid artery (ICA), basilar artery (BA), and vertebral artery (VA) in the prone (head centered-baseline) and supine positions (maximal rotation to both sides) in 23 premature infants aged between 3–5 days of life. We performed follow-up measurements in 17 infants 7–10 days later and in 16 infants at the corrected age of 1 month. There was no difference in mean CBFVs between the prone and supine position at the first investigation. At the third investigation, CBFVs were significantly higher in the supine compared to the prone position. The CBFVs of the ICA were higher than in the BA and VA. This difference was not influenced by the body position but increased with post-natal age more in the VA (159%) than in the BA (129%) and ICA (128%). Position dependency was not seen in the ICA perfusion. In the prone position, five infants showed an incomplete steal effect in the contralateral VA. There was no significant side difference in the CBFVs of the ICA and VA, but in the resistance indices in the VA (left >right). Conclusion: in premature newborns, position dependent changes of cerebral blood flow velocity develop with maturation and are most pronounced in the vertebrobasilar system. These changes are possibly due to compression of the vertebral artery by neck movement and suggest an individual risk of brainstem perfusion deficits that may be aggravated with age and head rotation in a prone position.

Die Tübinger Gaumenplatte — Ein innovatives Therapiekonzept bei Pierre-Robin-Sequenz

Infants with Pierre-Robin sequence (PRS) may suffer severe upper airway obstruction resulting in hypoxemia that is difficult to treat. We are currently evaluating a new therapeutic approach involving an oral appliance that widens the pharynx by pulling the base of the tongue forward using a preepiglottic baton. Here we present a patient treated with this device who showed a decrease in his desaturation index from 50 to < 1.SummaryInfants with Pierre-Robin sequence (PRS) may suffer severe upper airway obstruction resulting in hypoxemia that is difficult to treat. We are currently evaluating a new therapeutic approach involving an oral appliance that widens the pharynx by pulling the base of the tongue forward using a preepiglottic baton. Here we present a patient treated with this device who showed a decrease in his desaturation index from 50 to <1.ZusammenfassungSäuglinge mit Pierre-Robin-Sequenz zeigen häufig schwere Atemwegsobstruktionen mit Hypoxämie. Bisherige Behandlungsoptionen sind meist unbefriedigend. Wir führen derzeit eine Evaluierung einer Gaumenplatte mit velarem Sporn durch, die über eine Vorverlagerung des Zungengrundes zu einer Erweiterung des Pharynx beiträgt. Hier berichten wir einen exemplarischen Fall aus dieser Evaluationsstudie, bei dem es unter Therapie zu einem Rückgang der Hypoxiehäufigkeit von 50 auf <1/h kam.

The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates

Background:The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PICD) of immune effector cells such as monocytes. PICD from cord blood monocytes (CBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro.Methods:PBMOs, CBMOs, and Fas (CD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein–labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and CD95L secretion was quantified by enzyme-linked immunosorbent assay.Results:We demonstrate the involvement of the CD95/CD95 ligand pathway (CD95/CD95L) in PICD and provide evidence that diminished CD95L secretion by CBMOs may result in prolonged activation of neonatal immune effector cells.Conclusion:These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.