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STUDY OBJECTIVES Pulse-oximetry (SpO2 ) allows the identification of important clinical physiology. However, summary statistics such as mean values and desaturation incidence do not capture the complexity of the information contained within continuous recordings. The aim of this study was to develop an objective method to quantify important SpO2 characteristics; and assess its utility in healthy infant and preterm neonate cohorts. METHODS An algorithm was developed to calculate the desaturation incidence, depth, and duration. These variables are presented using three plots: SpO2 cumulative-frequency relationship; desaturation-depth versus incidence; desaturation-duration versus incidence. This method was applied to two populations who underwent nocturnal pulse-oximetry: (1) thirty-four healthy term infants studied at 2-weeks, 3, 6, 12, and 24-months of age and (2) thirty-seven neonates born

Background: IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the pre-school age-group. This randomised control trial (RCT) will primarily determine whether adenotonsillectomy improves IQ compared to no adenotonsillectomy after 12months, in preschool (3-5 year-old) children with mild to moderate OSA. Methods: This protocol is for an ongoing multi-centred RCT with a recruitment target of 210 subjects (105 in each arm). Children age 3-5 years with symptoms of OSA, are recruited through doctor referral, at the point of referral to the Ear Nose and Throat (ENT) services. Screening is initially with a questionnaire (Paediatric Sleep Questionnaire, PSQ) for symptoms of obstructive sleep apnoea (OSA). Where questionnaires are positive (suggestive of OSA) and ENT surgeons recommend them for adenotonsillectomy, they are invited to participate in POSTA. Baseline testing includes neurocognitive testing (IQ and psychometric evaluation with the neuropsychologist blinded to randomisation) and overnight polysomnography (PSG). Where the Obstructive Apnoea-Hypopnea Index (OAHI) from the PSG is

ObjectivePulse oximetry is used extensively in hospital and home settings to measure arterial oxygen saturation (SpO2). Interpretation of the trend and range of SpO2values observed in infants is currently limited by a lack of reference ranges using current devices, and may be augmented by development of cumulative frequency (CF) reference-curves. This study aims to provide reference oxygen saturation values from a prospective longitudinal cohort of healthy infants.DesignProspective longitudinal cohort study.SettingSleep-laboratory.Patients34 healthy term infants were enrolled, and studied at 2 weeks, 3, 6, 12 and 24 months of age (N=30, 25, 27, 26, 20, respectively).InterventionsFull overnight polysomnography, including 2 s averaging pulse oximetry (Masimo Radical).Main outcome measurementsSummary SpO2statistics (mean, median, 5th and 10th percentiles) and SpO2CF plots were calculated for each recording. CF reference-curves were then generated for each study age. Analyses were repeated with sleep-state stratifications and inclusion of manual artefact removal.ResultsMedian nocturnal SpO2values ranged between 98% and 99% over the first 2 years of life and the CF reference-curves shift right by 1% between 2 weeks and 3 months. CF reference-curves did not change with manual artefact removal during sleep and did not vary between rapid eye movement (REM) and non-REM sleep. Manual artefact removal did significantly change summary statistics and CF reference-curves during wake.ConclusionsSpO2CF curves provide an intuitive visual tool for evaluating whether an individual's nocturnal SpO2distribution falls within the range of healthy age-matched infants, thereby complementing summary statistics in the interpretation of extended oximetry recordings in infants.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of melatonin for non‐respiratory sleep disorders in typically developing children, with regard to improvement in sleep initiation, sleep maintenance and sleep scheduling, when compared with placebo, other medication for sleep disorders, psychological/behavioural therapy, light therapy or no treatment.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the role of melatonin for non‐respiratory sleep disorders in children with neurodevelopmental disorders for improvement in sleep initiation, sleep maintenance and sleep scheduling when compared with either placebo, other medication for sleep disorders, psychological/behavioural treatment, light therapy or no treatment.

Sighs are thought to have a role in regulating breathing control. They may preceed a central apnea (sigh-CA) or a pause (sigh-P), particularly in quiet sleep. Recent techniques characterizing cardiorespiratory synchronization (CRS) provide sensitive measures of cardiorespiratory coupling, which is an important factor in breathing control. We speculated that the strength of CRS and direction of cardiorespiratory coupling (DC), would differ between sigh-P and sigh-CA; before and after a sigh; and with maturation.Prospective study. CRS and DC were calculated from the respiratory signal and heart rate before and after sighs recorded during overnight polysomnography.Sleep laboratory.The data were selected from 15 subjects of a prospective cohort of 34 healthy infants at ages 2 weeks, 3 months and 6 months.N/A.Both CRS and respiratory modulation on heart rate (RMH) (negative DC index) were decreased around sigh-CA compared with sigh-P at all ages. Short-term CRS decreased after both sigh-P and sigh-CA in infants aged 2 weeks and 3 months. Long term CRS did not change before and after sigh-P or sigh-CA. CRS and RMH were increased at 3 months and 6 months compared to 2 weeks.A sigh was not found to be associated with apparent resetting of breathing control in healthy infants less than 6 months of age. Cardiorespiratory coupling appears to be a leading marker of changes in breathing control, preceding central apnea associated with a sigh.Nguyen CD; Dakin C; Yuill M; Crozier S; Wilson S. The effect of sigh on cardiorespiratory synchronization in healthy sleeping infants. SLEEP 2012;35(12):1643-1650.

Previous work has identified that non-linear variables calculated from respiratory data vary between sleep states, and that variables derived from the non-linear analytical tool recurrence quantification analysis (RQA) are accurate infant sleep state discriminators. This study aims to apply these discriminators to automatically classify 30 s epochs of infant sleep as REM, non-REM and wake. Polysomnograms were obtained from 25 healthy infants at 2 weeks, 3, 6 and 12 months of age, and manually sleep staged as wake, REM and non-REM. Inter-breath interval data were extracted from the respiratory inductive plethysmograph, and RQA applied to calculate radius, determinism and laminarity. Time-series statistic and spectral analysis variables were also calculated. A nested cross-validation method was used to identify the optimal feature subset, and to train and evaluate a linear discriminant analysis-based classifier. The RQA features radius and laminarity and were reliably selected. Mean agreement was 79.7, 84.9, 84.0 and 79.2 % at 2 weeks, 3, 6 and 12 months, and the classifier performed better than a comparison classifier not including RQA variables. The performance of this sleep-staging tool compares favourably with inter-human agreement rates, and improves upon previous systems using only respiratory data. Applications include diagnostic screening and population-based sleep research.

Non-invasive monitoring of breathing is a holy grail in paediatric respiratory, neonatal and sleep medicine. Respiratory rate is a key marker for the surveillance of sick infants and children (1-3), while repeated infant apnoeic episodes are associated with an increased risk of apparent life-threatening events (4). In clinical pulse oximetry, the photoplethysmographic (pleth) signal is assessed mainly to infer the validity of measured arterial oxygen saturation. This article is protected by copyright. All rights reserved.

Introduction: Sighs (deep inspirations) are thought to have an importantrole in restoring lung volume, resetting the mechanical propertiesof lung tissue and in changing neurorespiratory control. Especially, inquiet or non-rapid eye movement sleep, sighs may be followed bycentral apnea. Sighs reduce in frequency with maturation over the fi rstyear of life. We speculated that strength of cardiorespiratory synchronization(CS) and direction of cardiorespiratory coupling (DC), as ameasure of neurorespiratory control, would differ before and after sigh,and between sighs with and without central apnea, and that there wouldbe a maturational effect.Methodology: CS and DC were assessed by a phase dynamics methodpreceding and following sigh (with and without central apnea) in 15healthy infants at 2 weeks, 3 months and 6 months of age. The CSindex varied from 0 (unsynchronized) to 1 (perfectly synchronized).The DC index varies from −1 (if the direction of coupling is from respirationto heart rate) to 1 (in the opposite directional coupling fromheart rate to respiration), and −1 < DC index < 1 indicates bidirectionalcoupling.Results and discussion: Our results show a signifi cant decrease in CSand respiratory modulation on heart rate (RMH) (interpreted by “negative”DC index) prior to sighs with central apnea compared to sighsalone. Prior to a sigh, CS index was lower with sigh followed by centralapnea (0.58, 0.66, 0.64 at 2 weeks, 3 months and 6 months of age,respectively) than with sigh alone (0.63, 0.71, 0.76, respectively). Onthe other hand, prior to a sigh, DC index was higher with sigh followedby central apnea (−0.45, −0.67, −0.77 at 2 weeks, 3 months and6 months of age, respectively) than with sigh alone from (−0.50, −0.79,−0.80, respectively). We found that RMH increased after a sigh (withor without central apnea), suggesting the involvement of sighs in regulationand resetting of the neurorespiratory controller. Using neonataldata as a reference, CS and RMH increased at 3 months and furtherincreased at 6 months of age. The greatest change was observed between2 weeks and 3 months of age.Conclusion: CS in infants changes with maturation and is differentbefore a sigh with and without central apnea as well as changes beforeand after a sigh, suggesting a neuroregulatory role of sigh.

Introduction: Actigraphy has grown in popularity as an additional measure of sleep behaviour in recent years. The extent of its role in sleep medicine is unclear, perhaps due to the low temporal resolution of commercial measurement systems available. Such systems typically monitor only a single location and do not record data synchronised with PSG systems meaning that temporal correlation between eventsobserved in other channels and actigraphy is difficult to ascertain. Further, conventional actigraphy records only summarised activity counts, implying that morphologically different movements may result in the same or similar activity counts. The aim of this technical case study was to directly compare data recorded using a Continuous Multisite Accelerometry System (CMAS) to an Actiwatch (TM).Method: A male test subject wore an Actiwatch MiniMotionlogger (TM) on the left wrist, and the CMAS with accelerometers located on left wrist and middle fi nger, left ankle and great toe, and the sternal notch for an overnight sleep period.Results: A number of interesting features were identifi ed including (A) Movement recorded on ankle and toe, in absence of movement from other channels indicating a kick of that leg; (B) Movement recorded on finger in absence of wrist movement indicating a finger twitch; (C) Movement in all accelerometry channels with a change in posture; and (D) Series of movements recorded only in toe accelerometry channel.Discussion: CMAS was able to identify and characterise subject movements, which were not able to be differentiated using the Actiwatch (TM). The multisite nature of the system detects movements which are not observed on Actiwatch.

Electrical impedance tomography (EIT) has been used to study regional ventilation distribution in neonatal and paediatric lung disease; however, little information has been obtained in healthy newborns and infants. Data on regional ventilation distribution and regional filling characteristics were obtained using EIT in the neonatal period, at 3 and 6 months of age, in spontaneously breathing infants during non-rapid eye movement sleep. Regional ventilation distribution was described using regional end-expiratory and end-inspiratory impedance amplitudes, and geometric centre of ventilation. Regional filling characteristics were described with the phase lag or lead of the regional impedance change in comparison to global impedance change. 32 infants were measured in the supine position. Regional impedance amplitudes increased with age but regional ventilation distribution remained unchanged in all infants at any age, with the dependent (posterior) lung always better ventilated. Regional filling characteristics showed that the dependent lung filled during inspiration before the nondependent lung during all follow-up measurements. Regional ventilation distribution and regional filling characteristics remained unchanged over the first 6 months of life, and the results obtained on regional ventilation distribution are very similar to those in adult subjects.

Breathing patterns are characteristically different between infant active sleep (AS) and quiet sleep (QS), and statistical quantifications of interbreath interval (IBI) data have previously been used to discriminate between infant sleep states. It has also been identified that breathing patterns are governed by a nonlinear controller. This study aims to investigate whether nonlinear quantifications of infant IBI data are characteristically different between AS and QS, and whether they may be used to discriminate between these infant sleep states. Polysomnograms were obtained from 24 healthy infants at six months of age. Periods of AS and QS were identified, and IBI data extracted. Recurrence quantification analysis (RQA) was applied to each period, and recurrence calculated for a fixed radius in the range of 0-8 in steps of 0.02, and embedding dimensions of 4, 6, 8, and 16. When a threshold classifier was trained, the RQA variable recurrence was able to correctly classify 94.3% of periods in a test dataset. It was concluded that RQA of IBI data is able to accurately discriminate between infant sleep states. This is a promising step toward development of a minimal-channel automatic sleep state classification system.

Background: In adults, ventilation is preferentially distributed towards the dependent lung. A reversal of the adult pattern has been observed in infants using radionuclide ventilation scanning. But these results have been obtained in infants and children with lung disease. In this study we investigate whether healthy infants have a similar reverse pattern of ventilation distribution. Study Design: Measurement of regional ventilation distribution in healthy newborn infants during non-REM sleep in comparison to adults. Methods: Twenty-four healthy newborns and 13 adults were investigated with electrical impedance tomography (EIT) in supine and prone position. Regional ventilation distribution was assessed with profiles of relative impedance change. The phase lag between dependent and non-dependent ventilation was calculated as a measure of asynchronous ventilation. Results: In newborns and adults the geometric center of ventilation was centrally located in the lung at 52.2 +/- 6.2% from anterior to posterior and at 50.5 +/- 14.7%, respectively Using impedance profiles, ventilation was equally distributed to the dependent and non-dependent lung regions in newborns. Ventilation distribution in adults was similar Phase lag characteristics of the impedance signal showed that infants had slower emptying of the dependent lung than adults. Conclusion: The speculated reverse pattern of regional ventilation distribution in healthy infants compared to adults could not be demonstrated. Gravity had little effect on ventilation distribution in both infants and adults measured in supine and prone position. Pediatr Pulmonol. 2009;44:851-858. (C) 2009 Wiley-Liss, Inc.

It is well known that breathing patterns vary with infant sleep states. However, development of an automated sleep scoring tool based on conventional statistical analysis of breathing patterns has proven problematic. Recent work has demonstrated that non-linear properties of breathing patterns vary with sleep states and that analysis with nonlinear tools such as recurrence plot analysis allows the accurate discrimination of sleep states. In this work we propose using a combination of statistical and non-linear analysis measures to automate the identification of infant sleep states using only breathing dynamics.

Aim: Polysomnography (PSG) is the current standard protocol for sleep disordered breathing (SDB) investigation in children. Presently, there are limited reliable screening tests for both central (CE) and obstructive (OE) respiratory events. This study compared three indices, derived from pulse oximetry and electrocardiogram ( ECG), with the PSG gold standard. These indices were heart rate (HR) variability, arterial blood oxygen de-saturation (SaO(2)) and pulse transit time (PTT). Methods: 15 children (12 male) from routine PSG studies were recruited (aged 3 - 14 years). The characteristics of the three indices were based on known criteria for respiratory events (RPE). Their estimation singly and in combination was evaluated with simultaneous scored PSG recordings. Results: 215 RPE and 215 tidal breathing events were analysed. For OE, the obtained sensitivity was HR (0.703), SaO(2) (0.047), PTT (0.750), considering all three indices (0) and either of the indices (0.828) while specificity was (0.891), (0.938), (0.922), (0.953) and (0.859) respectively. For CE, the sensitivity was HR (0.715), SaO(2) (0.278), PTT (0.662), considering all indices (0.040) and either of the indices (0.868) while specificity was (0.815), (0.954), (0.901), (0.960) and (0.762) accordingly. Conclusions: Preliminary findings herein suggest that the later combination of these non-invasive indices to be a promising screening method of SDB in children.

OBJECTIVES. There are conflicting data regarding the impact of breastfeeding on the development of asthma in late childhood. Our aim with this study was to investigate the relationship between breastfeeding and the prevalence of asthma in children at 14 years. METHODS. The Mater-University of Queensland Study of Pregnancy is a birth cohort of 7223 women and their infants recruited from a public antenatal clinic in Brisbane, Australia, between 1981 and 1984. Data regarding breastfeeding and the duration of breastfeeding were collected through the use of a questionnaire completed by the mother 6 months postdelivery, and the prevalence of asthma was determined through the use of a questionnaire completed by the mother 14 years postdelivery. RESULTS. Data regarding both breastfeeding and asthma were available for 4964 children. The prevalence of asthma in children at 14 years was 28.4%. Breastfeeding for ≥4 months was not found to have a significant effect on the prevalence of asthma in 14-year-olds. The unadjusted odds ratio of developing asthma at 14 years if the child was breastfed for ≥4 months was 1.03. The odds ratio of developing asthma did not change appreciably when allowance was made for potential confounding factors. CONCLUSION. Data from this study indicate that breastfeeding neither increases nor decreases the prevalence of asthma in children at 14 years.

High-resolution computed tomography (HRCT) is a sensitive technique for early visualisation and location of cystic fibrosis (CF) bronchopathology, and has been shown to detect acute reversible and chronic changes. It would be expected to correlate with markers of the underlying pathological processes, such as sputum cytokines and cytology, as well as with pulmonary function tests (PFTs). Our aim was to study the relationship between PFTs, sputum cytology, and sputum cytokine interleukin-8 (IL-8) and HRCT in CIF patients. Prospective standardized collection of sputum samples was performed at the time of routine annual high-resolution CT scans. Forced expired volume in 1 sec (FEV1) and forced vital capacity (FVC) were recorded. Sputum processing was selective, with dispersal by the three-enzyme technique. IL-8 measurements were by kit assay. HRCT scans were scored by a pediatric radiologist, blinded to clinical condition, using a modified Bhalla score.Forty-three CT scans were performed on 34 children with CIF between March 1998 and April 2000. Mean age was 12.3 years (range, 6-21 years), FEV1 (% predicted) was 67% (range, 23-120%), and mean modified Bhalla score was 11.2 (range, 0-22). Sputum IL-8 concentration (mean, 86; range, 4-150 ng/mL) and total cell count (mean, 31.9 x 10(6)/mL; range, 21.8-42.0 x 10(6)/mL) were high. FEV1 and FVC correlated with modified Bhalla score (r = -0.66, P < 0.0001 for both), and most individual components of the score, especially mosaic perfusion (r = -0.64, r = -0.61 respectively, P < 0.0001) and extent of bronchiectasis (r = -0.61, P < 0.0001 for both). The combination of these two predicted 58% of the variability in FEV1 on analysis of variance (P < 0.0001). Sputum total cell count correlated weakly with modified Bhalla score (r = 0.38, P < 0.05) and with FEV1 and FVC (r = -0.36, P < 0.05; and r= -0.46, P < 0.01). Differential cell counts, cell viability, and IL-8 did not correlate with modified Bhalla scores, or with reversible components such as mucus plugging, centrilobular nodules, or peribronchial thickening.In conclusion, pathological changes on HRCT correlated with lung function but not with sputum markers of inflammation. (C) 2002 Wiley-Liss, Inc.

BACKGROUND: We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. METHODS: Of 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. RESULTS: Eighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. CONCLUSIONS: CF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children.

Objectives: A hospital admission for asthma represents an opportunity to address and improve asthma control. The aims of this study were to compare the ambulatory care of children admitted to the intensive care unit (ICU) following a life-threatening asthma exacerbation with published guidelines of asthma management and to identify areas that could be targeted for change.Methods: A retrospective review of case notes of children admitted to the ICU with asthma over a 6-month period. Variables recorded were: demographic; asthma history (including prior pattern of asthma, hospital admissions, interval treatment and managing doctor); admission details (consultation of respiratory team and asthma educator); and discharge management.Results: There were 40 admissions of 38 children (24 males) with mean age 5.7 years (range 1.1-14 years). The majority (58%) had previous admissions for asthma (55 admissions in 22 children), with 23% of these to ICU. Sixty three per cent of those with previous admissions had persistent asthma, but only 29% were on inhaled corticosteroid (ICS). Most (60%) were managed by their local medical officer (LMO). Use of ICS was more likely if managed by a paediatrician. A respiratory subspecialist was consulted in 42% and the asthma educator in 70% of ICU admissions. Discharge medication included ICS in 74%, with no interval treatment in 18% of admissions. Follow up was by a respiratory subspecialist in 25% of cases.Conclusion: Asthma management before and after admission with life-threatening asthma did not conform to available guidelines. Persistent asthma was under-treated. Paediatricians were more likely to use interval treatment than LMO. We identified areas in which quality of care and outcome could be improved in this vulnerable group of asthmatics.

Introduction: Sighs (deep inspirations) are thought to have an important role in restoring lung volume, resetting the mechanical properties of lung tissue and in resetting neurorespiratory control. In quiet or non-rapid eye movement sleep, sighs are often followed by post sigh central apnea. Sighs reduce in frequency with maturation over the first year of life. We speculate that cardiorespiratory synchronization (CRS), as a measure of neurorespiratory control, would differ between sigh with and without central apnea, and change with maturation. We also hypothesize that infants with chronic neonatal lung disease (CNLD) would display differences in CRS preceding sigh versus measurements derived from healthy infants.Methodology: Full overnight polysomnography (PSG) data was obtained from prospective cohorts of 34 healthy infants (aged 2 weeks, 3 months and 6 months old) and of 82 CNLD infants (aged 3-6 months old). Both groups were studied in room air. CRS strength was assessed by a phase synchronization method measuring coupling between breathing and heart beat obtained from the R-wave. The synchronization index varies from 0 (unsynchronized) to 1 (perfectly synchronized). Results: Our results show a significant decrease of CRS prior to sigh followed by a post sigh central apnea (sigh-PSCA) compared to sigh alone in both healthy and CNLD infants. In the healthy infant group, CRS index was lower with sigh-PSCA (0.59, 0.68, 0.69) at 2 weeks, 3 months and 6 months of age, respectively) than with sigh alone (0.65, 0.72, 0.79, respectively). In the CNLD group, CRS index was also lower with sigh-PSCA (0.66) than with sigh alone (0.71). Using healthy infant’s data at 2 weeks old as reference, CRS increased at 3 months of age and further increased at 6 months of age. The greatest change was observed between 2 weeks and 3 months of age.Conclusion: CRS changes with infant maturation. Post sigh central apnea is associated with a significant decrease in CRS preceding the apneic event.

Treatment of sleep disorders in visually impaired children is complicated by a complex pathophysiology, a high incidence of sleep disorders in this population, and a dearth of management options. The significant impact on the health of these children and distress to their caregivers warrant a systematic assessment of the published literature on therapeutic approaches.This systematic review aims to assess the current therapeutic options in the management of sleep disorders in visually impaired children to identify knowledge gaps and guide future research.A search of primary literature was conducted using the bibliographic databases PubMed (1980-August 2010), EMBASE (1990-August 2010), Science Citation Index Expanded (1990-August 2010), and CINHAL (1992-August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL). Additional studies were identified through snowballing search techniques (manually by searching retrieved references and electronically by using citation-tracking software). Search terms included behavioral treatment, children, circadian rhythm, hypnosedatives, intellectual disability, light therapy, melatonin, phototherapy, random allocation, randomized controlled trial (RCT), sleep disorder, and visual impairment. Randomized and quasi-randomized clinical trials of therapeutic options (behavioral treatment, light therapy, melatonin, or hypnosedatives) used in participants aged 3 months to 18 years who had both a visual impairment and a sleep disorder were included. Independent extraction of articles was performed by 2 authors using predefined data fields, including quality of the therapeutic options, based on the Strength of Recommendation Taxonomy evidence-rating system.Two RCTs were retrieved for melatonin, with improved effect on sleep latency (P = 0.019 and P0.05, respectively). However, separate analysis for visual impairment was not conducted. No RCTs were retrieved for behavioral intervention, light therapy, or hypnosedatives. Three studies using behavioral therapy (2 case reports and 1 case series) anecdotally showed improvement in sleep habit. No improvement in sleep rhythm was observed with a case series applying light therapy as an intervention.Children with visual impairment and sleep disorders are a heterogeneous patient group, making diagnosis and treatment difficult. RCTs on treatment options remain in their infancy, with a lack of evidence for appropriate therapeutic strategies. Trials across a range of selected diagnoses need to be conducted with adequate sample populations to differentiate the efficacy of 4 different treatment modalities (behavioral therapy, light therapy, melatonin, and hypnosedatives) as agents for improving sleep.

Objective This study characterises and describes the maturational evolution of the healthy infant sleep electroencephalogram (EEG) longitudinally from 2 weeks to 24 months of age, by means of power spectral analysis. Methods A prospective cohort of 34 healthy infants underwent overnight polysomnography (PSG) at 2 weeks, and at 3, 6, 12 and 24 months of age. Sleep epochs were scored as Active Sleep (AS) and Quiet Sleep (QS) at 2 weeks of age and as Rapid Eye Movement (REM) and Non-REM (NREM) stages from 3 months onwards. Representative epochs were used to generate the EEG power spectra, from the central C3 derivation. These were analysed visually and quantitatively in AS/REM and QS/NREM sleep in the following bandwidths: delta (0.5–4 Hz); theta (4–8 Hz); alpha (8–11 Hz); sigma (11–15 Hz) and 0.5–25 Hz. Results Sleep EEG (central derivation) power spectra changed significantly in the different bandwidths as the infants matured. The emergence of a peak in the sigma bandwidth in NREM N2 sleep corresponded with the development of sleep spindles. Maturational changes were also seen in NREM N3 and in theta and alpha bandwidths in both AS/REM and QS/NREM. Conclusions Sleep EEG power spectra characteristics in healthy infants evolve in keeping with maturation and neurodevelopmental milestones. Significance This study provides an atlas of healthy infant sleep EEG in the early years of life, providing a basis for association with other neurodevelopmental measures and a normative dataset on which disease may be discriminated.

In adults, ventilation is preferentially distributed towards the dependent lung. A reversal of the adult pattern has been observed in infants using radionuclide ventilation scanning. But these results have been obtained in infants and children with lung disease. In this study we investigate whether healthy infants have a similar reverse pattern of ventilation distribution.Measurement of regional ventilation distribution in healthy newborn infants during non-REM sleep in comparison to adults.Twenty-four healthy newborns and 13 adults were investigated with electrical impedance tomography (EIT) in supine and prone position. Regional ventilation distribution was assessed with profiles of relative impedance change. The phase lag between dependent and non-dependent ventilation was calculated as a measure of asynchronous ventilation.In newborns and adults the geometric center of ventilation was centrally located in the lung at 52.2 +/- 6.2% from anterior to posterior and at 50.5 +/- 14.7%, respectively. Using impedance profiles, ventilation was equally distributed to the dependent and non-dependent lung regions in newborns. Ventilation distribution in adults was similar. Phase lag characteristics of the impedance signal showed that infants had slower emptying of the dependent lung than adults.The speculated reverse pattern of regional ventilation distribution in healthy infants compared to adults could not be demonstrated. Gravity had little effect on ventilation distribution in both infants and adults measured in supine and prone position.

Objective: Our aim was to determine the safety of BAL in young children

Theoretically, any participating parameter in a non-linear system represents the dynamics of the whole system. Taken's time delay embedding theory provides the fundamental basis for allowing non-linear analysis to be performed on physiological, time-series data. In practice, only one measurable parameter is required to be measured to convey an accurate representation of the system dynamics. In this paper, the infant respiratory control system is represented using three variables-a digitally sampled respiratory inductive plethysmography waveform, and the derived parameters tidal volume and inter-breath interval time series data. For 14 healthy infants, these data streams were analysed using recurrence plot analysis across one night of sleep. The measured attractor size of these variables followed the same qualitative trends across the nights study. Results suggest that the attractor size measures of the derived IBI and tidal volume are representative surrogates for the raw respiratory waveform. The extent to which the relative attractor sizes of IBI and tidal volume remain constant through changing sleep state could potentially be used to quantify pathology, or maturation of breathing control.

A 7-month old infant presented with an effusion and multiple lesions in his spleen. A diagnosis of lymphangiomatosis was made based on chylous effusion and an MRI demonstrating numerous enhancing lesions within the spleen on T2-weighed images. Conservative measures, including the withdrawal of feeds and octreotide, did not significantly reduce the rate of chyle production and increasing requirement for respiratory support. Resection of the patient's spleen and partial pleurectomy were associated with a dramatic improvement in his condition. At 27 months the patient was well with no evidence of further lymphangiomas or a recurrence of his chylothoraces.

In 58 patients with transfusion dependent anemia, we compared cardiac function, as assessed by gated pooled cardiac scan at rest and during exercise stress, with liver iron concentrations (LIC) as determined by adequate biopsy samples. There was no relationship between LIC and cardiac function and deaths occurred in patients with LIC levels below those that are usually associated with cardiac death. LIC should not be used as a surrogate to determine risk of cardiac complications but purely for management of the hepatic iron load. Other methods, particularly magnetic resonance imaging, should be used to assess cardiac iron overload.

Pulse oximetry is commonly used as an arterial blood oxygen saturation (SaO2) measure. However, its other serial output, the photoplethysmography (PPG) signal, is not as well studied. Raw PPG signals can be used to estimate cardiovascular measures like pulse transit time (PTT) and possibly heart rate (HR). These timing-related measurements are heavily dependent on the minimal variability in phase delay of the PPG signals. Masimo SET Rad-9 and Novametrix Oxypleth oximeters were investigated for their PPG phase characteristics on nine healthy adults. To facilitate comparison, PPG signals were acquired from fingers on the same hand in a random fashion. Results showed that mean PTT variations acquired from the Masimo oximeter (37.89 ms) were much greater than the Novametrix (5.66 ms). Documented evidence suggests that 1 ms variation in PTT is equivalent to 1 mmHg change in blood pressure. Moreover, the PTT trend derived from the Masimo oximeter can be mistaken as obstructive sleep apnoeas based on the known criteria. HR comparison was evaluated against estimates attained from an electrocardiogram (ECG). Novametrix differed from ECG by 0.71+/-0.58% (p0.05) while Masimo differed by 4.51+/-3.66% (p0.05). Modern oximeters can be attractive for their improved SaO2 measurement. However, using raw PPG signals obtained directly from these oximeters for timing-related measurements warrants further investigations.

Our aim was to study the effect of lower airway infection on clinical parameters, pulmonary function tests, and inflammation in clinically stable infants and young children with cystic fibrosis (CF). To accomplish this goal, a prospective cohort of screened CF patients under 4 years of age were studied, using elective anesthesia and intubation for: passive respiratory mechanics (single breath occlusion passive deflation) and lung volumes (nitrogen washout), under neuromuscular blockade; and bronchoalveolar lavage (BAL) of 3 main bronchi for cytology, cytokine interleukin (IL)-8, and quantitative microbiology. There were 22 children studied, with a mean age of 23.2 months (6.7-44 months). A greater relative risk of lower airway pathogens was associated with prior respiratory admission (3.60, 95% confidence interval [CI] 2.87-4.51), history of asthma (1.75, 95% CI 1.52-2.03), and chronic symptoms (1.50, 95% CI 1.23-1.83), especially wheeze (1.88, 95% CI 1.61-2.19). Lower respiratory pathogens (or = 10 cfu/ml BAL) were found in 14 out of 22, and greater than 10(5) cfu/ml in 8 out of 22 subjects. The level of pathogens in BAL (log10 cfu/ml) explained 78% of the variability in percent neutrophils and 34% of the variability in IL-8 levels. Pathogen level also correlated with pulmonary function tests of specific respiratory system compliance (r -0.49, p = 0.02) and functional residual capacity over total lung capacity (r 0.49, p = 0.03). We conclude that the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance, and degree of air trapping.

Nebulized epinephrine has been advocated as a treatment for airway obstruction in infants with bronchiolitis; however, its effect on respiratory mechanics and gas exchange has been poorly documented to date. We performed a preinterventional and postinterventional study with primary outcome measures of mechanics (measured by single-breath occlusion passive deflation) and oxygenation and ventilation indices in order to measure the effects of nebulized epinephrine in infants requiring mechanical ventilation for RSV-positive bronchiolitis. A two-compartment model was used to describe respiratory mechanics in patients with nonlinear flow-volume curves. Nebulized epinephrine (0.5 mg/kg) was administered to 15 patients (median age, 0.19 yr; weight, 4.4 kg). Resistance decreased significantly in slow and fast compartments in 87 and 70% of patients, respectively. Median resistance in the slow compartment decreased from 0.427 to 0.198 cm H2O/ml/s (p = 0.0015) and in the fast compartment from 0.167 to 0.116 cm H2O/ ml/s (p = 0.018). Compliance, oxygenation index, and ventilation index were not significantly changed after administration of epinephrine. We conclude that nebulized epinephrine substantially improves respiratory system resistance but not oxygenation or ventilation indices. This may be because of the effects of epinephrine on oxygen consumption or ventilation-perfusion matching.

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus,74% or26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.

Background: Children with Prader Willi syndrome (PWS) are at risk of sleep disordered breathing involving central and obstructive components. PWS patients are known to have abnormal responses to hypoxia and hypercapnoea, an increased incidence of Obstructive Sleep Apnoea [OSA] and hypersomnolence when older not explained by obesity alone. As infants, many present with delay in central control of breathing during sleep. Hypersomnolence and indeed narcolepsy have been reported in this group of patients. Modafinil is a wake promoting agent but a pharmacological profile that is distinct from sympathomimetic amines, which increase wakefulness by other mechanisms. Modafinil does not bind to most of the potentially relevant receptors for sleep/wake regulation, including those for noradrenaline, serotonin, dopamine, GABA, adenosine, histamine-3 and benzodiazepines. Methods: Polysomnography (PSG) and multiple sleep latency testing [MSLT] was performed on PWS children attending a multidisciplinary clinic. Children who met criteria for narcolepsy were treated according to narcolepsy guidelines. Those who were hypersomnolent were assessed and three patients were trialed on Modafinil (a novel wake promoting agent). Results: Three children were studied, aged 7–13 years. Two were treated within a placebo controlled cross-over design. There was a significant difference in behavioural parameters as measured by teacher and parent. The other had significant hypersomnolence with a BMI in the obese range. Treatment resulted in a dramatic improvement in behaviour, activity and BMI. Conclusion: Children with Prader Willi syndrome and hypersomnolence may benefit from treatment with modafinil.

Background: Children with Prader Willi syndrome (PWS) are at risk of sleep disordered breathing involving central and obstructive components. PWS patients are known to have abnormal responses to hypoxia and hypercapnoea, an increased incidence of Obstructive Sleep Apnoea [OSA] and hypersomnolence when older. As infants, many present with delay in central control of breathing during sleep and resultant hypoxia. This may have long term consequences for the phenotype. Methods: Polysomnography (PSG) and multiple sleep latency testing [MSLT] was performed on PWS children attending a multidisciplinary clinic. Sleep disorders and age of presentation were identified. EEG spectral analysis on infants was undertaken and compared to a group of typically developing infants. Genotype was established. Results: Results suggest that in children less than 2 years central hypoventilation is present in 100%. 10% of children older than five had normal studies and the rest had OSA+/central hypoventilation. 10% had central hypoventilation and hypersomnolence. Twenty-five children under 12 months of age were analysed separately. Improvements in central hypoventilation were seen in some infants as they matured. The relationship between this and development of mature EEG patterns was examined and is significantly different to EEG spectral analysis of normal infants studied at 3, 6 and 12 months. This was also related to the genotype of each infant. Conclusion: Infants with Prader Willi have a delay in neural maturity as reflected by EEG development of defined EEG sleep stages. All infants with Prader Willi should have a sleep study in infancy and appropriate therapy instigated if required. Hypersomnolence is generally associated with other sleep disorders.

Background: In children with cystic fibrosis (CF), tobramycin concentrations are monitored via the area under the plasma concentration time curve (AUC) approach. Currently, a minimum of 2 plasma concentrations of tobramycin within one dosing interval are required to estimate the AUC, which is costly, painful and blood collection is often difficult to coordinate. Aim: To evaluate the accuracy of tobramycin AUC estimated using 1 plasma concentration compared to AUC based on 2 plasma concentrations calculated using Bayesian software. Method: Data were collected from paediatric patients with CF prescribed once daily intravenous tobramycin. Each patient had 2 blood samples taken within a dosing interval (according to usual practice at the hospital) on 2 separate occasions during their admission. Data on tobramycin dosing and concentration, and patient demographics from the first occasion were entered into the Bayesian software, TCIWorks, to establish an individual patient’s pharmacokinetic model. Data from the second occasion were then also entered into TCIWorks to estimate 2 AUCs – from 1 (AUC 1 ) and 2 (AUC 2 ) plasma concentrations. The accuracy of each patient’s AUCs (AUC 1 and AUC 2 ) were then evaluated using a Bland-Altman analysis to describe bias relative to the mean of the two values. To show the benefits of good quality data when using TCIWorks, data were obtained and analysed from 2 patient groups. For group A patients, accurate sampling and administration times of the tobramycin infusion were obtained prospectively. Group B consisted of patients from group A plus additional patients who had data collected from a retrospective medical chart review. Results: Data were collected for 30 paediatric patients with CF – 14 in group A and 16 additional patients in group B. In group A, there was no significant bias relative to the mean of the values for AUC 1 and AUC 2 (mean bias 1; 95%CI -4.9–6.9). A similar result was seen in group B (mean bias -0.7; 95%CI 10–8.6) indicating that the 2 estimates of tobramycin AUC (using 1 and 2 blood samples) are not significantly different. Conclusion: Once an individual paediatric patient’s tobramycin pharmacokinetic model is determined with two blood samples using TCIWorks, only one blood sample is required to estimate an AUC for tobramycin. J Pharm Pract Res 2011; 41: 183-7.

Background Exogenous melatonin helps in regulating the circadian rhythm and is widely used for the management of sleep disorders in visually impaired children. Objectives The aim of the review was to assess melatonin therapy for treatment of non-respiratory sleep disorders in visually impaired children, with regard to improvement in sleep habit, sleep scheduling and sleep maintenance, when compared with placebo or no treatment. Search strategy We searched the following databases between February 2011 and July 2011: the Cochrane Central Register of Controlled Trials (CENTRAL) 2011(1) searched on 4th February 2011;MEDLINE (1950 to JuneWeek 3, 2011) searched on 20th June 2011; EMBASE (1980 to June Week 4, 2011) searched on 7th July 2011; CINAHL (1937 to 21 September 2011); the metaRegister of Controlled Trials (this includes ClinicalTrial.gov) searched 20 July 2011, and reference lists of papers identified after initial screening. Selection criteria We planned to include randomized controlled trials (RCTs) and quasi-RCTs, including cross-over studies.Treatmentwould be exogenous melatonin. Control groups could be placebo, other medication for sleep disorders or no treatment. Outcomes sought were improved sleep with regard to timing and duration, quality of life and adverse events. Data collection and analysis Three review authors independently assessed trials for inclusion in the review. Main results We did not find any studies fulfilling the inclusion criteria, therefore no outcome data are reported. We identified nine studies after initial screening and, after further evaluation, we excluded these. The excluded studies involved a total of 163 individuals aged two years to 18 years. We excluded studies for three main reasons: they were non-randomized or case series studies, they were studies of people over 18 years of age or even where the study was randomised, the study population was mixed and results pertaining to the visually impaired cohort could not be independently evaluated. No significant adverse effects of melatonin were reported in these excluded studies. Authors' conclusions There is currently no high quality data to support or refute the use of melatonin for sleep disorders in visually impaired children. Placebo-controlled trials examining important clinical outcomes such as sleep quality, sleep latency, duration of sleep and night-time awakenings are needed. As the numbers of children meeting study inclusion criteria are likely to be low at individual sites, multicentre collaboration between developmental paediatricians, sleep physicians and other health care professionals is essential to achieve sufficient sample size for controlled studies. Such collaboration would help facilitate local recruitment atmultiple sites, with study oversight being provided by paediatricians with expertise in sleep disorders. Participation of collaborators with experience in evidence-based practice research is also desirable due to the lack of protocols on melatonin therapy in the target population.