Teaching and learning in biophotonics: Crossing the bridge between educators and students.

As a rapidly growing field, biophotonics demonstrates an increasingly higher demand for interdisciplinary professionals and requires the implementation of a structured approach to educational and outreach activities focused on appropriate curriculum, and teaching and learning for audiences with diverse technical backgrounds and learning styles. Our study shows the main findings upon applying this approach to biophotonics workshops delivered 2 consecutive years while updating and improving learning outcomes, teaching strategies, workshop content based on student and teacher feedback. We provided resources for a variety of lecture-based, experimental, computer simulation activities. Quality of subject matter, teaching, and overall learning was rated as "Very good" or "Good" by 88%, 76%, and 82% of students in average, respectively. Application of our teaching strategies and materials during short- and long-term workshops/courses could potentially increase the interest in pursuing careers in the biophotonics field and related areas, leading to standardized approaches in designing education and outreach events across centers.

Allergic disease, sleep problems, and psychological distress in children recruited from the general community.

BACKGROUND: It is not clear which allergic disease is most strongly related to which sleep problem and whether sleep problems may mediate the association between allergic disease and psychological distress. There is also a need for more community-based studies using nonreferred samples. OBJECTIVE: To evaluate the association between individual allergic diseases and sleep problems and test whether the association between allergic disease and psychological distress is mediated through sleep problems. METHODS: Parents of 1449 Australian children aged 6 to 10 years recruited from the general community, completed measures of sleep problems (Pediatric Sleep Survey Instrument), psychological distress (Strengths and Difficulties Questionnaire), and frequency of allergic diseases. RESULTS: Sleep and psychological distress scores were in the reference range. After controlling for coexisting allergic diseases, allergic rhinitis was associated with sleep routine problems, morning tiredness, night arousals, sleep disordered breathing and restless sleep; asthma with sleep routine problems, sleep disordered breathing and restless sleep; and eczema with restless sleep. Path analyses revealed that sleep problems mediated the association between asthma and allergic rhinitis but not eczema with psychological distress. CONCLUSION: In this nonreferred community sample, the frequency of sleep problems and psychological distress was lower than that typically reported in children referred to specialized centers. However, allergic rhinitis was associated with a broad range of sleep problems and to a lesser extent in children with asthma and least in children with eczema. Path analysis revealed that the association between allergic disease and psychological distress was mediated through sleep problems, highlighting the importance of assessing sleep health in children with allergic disease.

Short report: Sleep talking and mental health in children with developmental problems and typically developing children.

BACKGROUND: Sleep talking although often considered benign is associated with poor mental health. However, it remains to be tested whether this association may be better explained by the presence of co-morbid sleep problems and the presence in survey samples of children with development disorders who tend to report a higher frequency of both sleep problems and poor mental health. AIM: The aim of the present study was to examine the association between sleep talking and mental health after controlling for comorbid sleep problems in typically developing children and children with developmental problems. METHODS: Parents of typically developing children (n = 1609) and children with either intellectual or developmental delay (n = 128) aged 5-10 years completed an omnibus survey which was administered through participating South Australian primary schools assessing mental health (Strengths and Difficulties Questionnaire) and sleep problems (Paediatric Sleep Survey Instrument). RESULTS: After controlling for co-morbid sleep problems, regression analyses revealed that sleep talking in typically developing children was an independent but weak predictor of worse emotional symptoms, conduct problems and peer relationship problems. By contrast, only a single significant association was observed in children with developmental problems. Paradoxically, sleep talking was associated with better prosocial behaviour. CONCLUSION: It is suggested that in typically developing children with a history of sleep talking, mental health merits evaluation at clinical interview while in both typically developing children and children with developmental problems, co-morbid sleep problems merit evaluation.

Utilisation of machine learning to predict surgical candidates for the treatment of childhood upper airway obstruction.

OBJECTIVE: To investigate the effect of adenotonsillectomy on OSAS symptoms based on a data-driven approach and thereby identify criteria that may help avoid unnecessary surgery in children with OSAS. METHODS: In 323 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (eAT; N = 165) or a strategy of watchful waiting with supportive care (WWSC; N = 158), the apnea-hypopnea index, heart period pattern dynamics, and thoraco-abdominal asynchrony measurements from overnight polysomnography (PSG) were measured. Using machine learning, all children were classified into one of two different clusters based on those features. The cluster transitions between follow-up and baseline PSG were investigated for each to predict those children who recovered spontaneously, following surgery and those who did not benefit from surgery. RESULTS: The two clusters showed significant differences in OSAS symptoms, where children assigned in cluster A had fewer physiological and neurophysiological symptoms than cluster B. Whilst the majority of children were assigned to cluster A, those children who underwent surgery were more likely to stay in cluster A after seven months. Those children who were in cluster B at baseline PSG were more likely to have their symptoms reversed via surgery. Children who were assigned to cluster B at both baseline and 7 months after surgery had significantly higher end-tidal carbon dioxide at baseline. Children who spontaneously changed from cluster B to A presented highly problematic ratings in behaviour and emotional regulation at baseline. CONCLUSIONS: Data-driven analysis demonstrated that AT helps to reverse and to prevent the worsening of the pathophysiological symptoms in children with OSAS. Multiple pathophysiological markers used with machine learning can capture more comprehensive information on childhood OSAS. Children with mild physiological and neurophysiological symptoms could avoid AT, and children who have UAO symptoms post AT may have sleep-related hypoventilation disease which requires further investigation. Furthermore, the findings may help surgeons more accurately predict children on whom they should perform AT.

Quality-of-life but not behavior improves 48-months post-adenotonsillectomy in children with SDB.

BACKGROUND: Long term follow-up studies (>12 mths) of changes in behavior and quality-of-life (QoL) in children with sleep disordered breathing (SDB) post-adenotonsillectomy are limited and there is a lack of consensus in the reported findings. The aim of this study was to evaluate children's sleep, QoL and behavior at baseline and 6 mths and 48 mths post-adenotonsillectomy for clinically diagnosed SDB. METHODS: This prospective longitudinal study of children aged 3-12 y recruited from a Children's Hospital otolaryngology clinic compared polysomnographic parameters, behavior (Child Behavior Checklist; CBCL) and QoL (OSA-18) at baseline, 6mths and 48mths post-adenotonsillectomy and compared these parameters to healthy non-snoring controls recruited from the general community at the same time points. RESULTS: Sixty-four children completed sleep, behavior and QoL assessments (SDB = 20M/9F, Controls = 18M/17F) at all three time points. Sleep and ventilatory parameters significantly improved in children with SDB with minimal residual obstruction evident at 48 mths post-adenotonsillectomy. Compared to baseline, OSA-18 scores significantly improved post-adenotonsillectomy in children with SDB and were equivalent to the scores of controls at 6 mths and 48 mths post-AT. No significant improvement was observed in behavior in children with SDB post-adenotonsillectomy over the same time period. CONCLUSION: Baseline deficits in sleep and QoL in children with SDB were normalized at 6 mths post-adenotonsillectomy and gains were maintained at 48 mths post-adenotonsillectomy. Children with SDB did not show significant gains in behavior either at 6 mths or 48 mths post-adenotonsillectomy.

Increased Platelet Aggregation in Children and Adolescents with Sleep-disordered Breathing.

Rationale: Sleep-disordered breathing (SDB) is associated with increased vascular resistance in children and adults. Persistent increased vascular resistance damages vascular endothelial cells-a marker of which is increased platelet activation.Objectives: This study compared whole-blood impedance platelet aggregation in children with clinically diagnosed SDB warranting adenotonsillectomy and healthy control subjects.Methods: Thirty children who had SDB warranting intervention clinically diagnosed by experienced pediatric otolaryngologists were recruited from adenotonsillectomy waitlists, and 20 healthy children from the community underwent overnight polysomnography to determine SDB severity (obstructive apnea-hypopnea index). Snoring frequency was collected from parents. In the morning, a fasting blood sample was taken, and whole-blood platelet aggregation was measured.Measurements and Main Results: Children with SDB exhibited increased platelet aggregation to TRAP (thrombin receptor-activating peptide) (children with SDB = 114.8 aggregation units [AU] vs. control subjects = 98.0 AU; P < 0.05) and COL antibody (96.7 vs. 82.2 AU; P < 0.05) and an increased trend in ADP antibody (82.3 vs. 69.2 AU; P < 0.07) but not aspirin dialuminate (82.1 vs. 79.5 AU; P > 0.05). No significant association was observed between either the obstructive apnea-hypopnea index and any aggregation parameter, but parental report of snoring was positively associated with TRAP aggregation (Kendall's τ-c = 0.23; P < 0.05).Conclusions: The finding of increased platelet aggregation is consistent with endothelial damage. This suggests that the profile of cardiovascular changes noted in adults with SDB may also occur in children with SDB.

The microbial abundance dynamics of the paediatric oral cavity before and after sleep.

Objective: Microhabitats in the oral cavity differ in microbial taxonomy. However, abundance variations of bacterial and viral communities within these microhabitats are not fully understood. Aims and Hypothesis: To assess the spatial distribution and dynamics of the microbial abundances within 6 microhabitats of the oral cavity before and after sleep. We hypothesise that the abundance distributions of these microbial communities will differ among oral sites. Methods: Using flow cytometry, bacterial and virus-like particle (VLP) abundances were enumerated for 6 oral microhabitats before and after sleep in 10 healthy paediatric sleepers. Results: Bacterial counts ranged from 7.2 ± 2.8 × 105 at the palate before sleep to 1.3 ± 0.2 × 108 at the back of the tongue after sleep, a difference of 187 times. VLPs ranged from 1.9 ± 1.0 × 106 at the palate before sleep to 9.2 ± 5.0 × 107 at the back of the tongue after sleep, a difference of 48 times. Conclusion: The oral cavity is a dynamic numerically heterogeneous environment where microbial communities can increase by a count of 100 million during sleep. Quantification of the paediatric oral microbiome complements taxonomic diversity information to show how biomass varies and shifts in space and time.

The Inconsistent Nature of Heart Rate Variability During Sleep in Normal Children and Adolescents.

Introduction: Cardiac function is modulated by multiple factors including exogenous (circadian rhythm) and endogenous (ultradian 90-110 min sleep cycle) factors. By evaluating heart rate variability (HRV) during sleep, we will better understand their influence on cardiac activity. The aim of this study was to evaluate HRV in the dark phase of the circadian rhythm during sleep in healthy children and adolescents. Methods: One 3 min segment of pre-sleep electrocardiography (EEG) and 3, 6 min segments of electrocardiography recorded during polysomnography from 75 healthy children and adolescents were sampled during progressive cycles of slow wave sleep (SWS1, SWS2, SWS3). Three, 3 min segments of rapid eye movement sleep (REM) were also assessed, with REM1 marked at the last REM period before awakening. Studies that recorded REM3 prior to SWS3 were used for assessment. HRV variables include the following time domain values: mean NN (average RR intervals over given time), SDNN (Standard Deviation of RR intervals), and RMSSD (root Mean Square of beat-to-beat Differences). Frequency domain values include: low frequency (LF), high frequency (HF), and LF:HF. Results: Mixed linear effects model analysis revealed a significant difference in time and frequency domain values between sleep cycles and stages. Mean NN was lowest (highest heart rate) during pre-sleep then significantly increased across SWS1-3. Mean NN in SWS1 was similar to all REM periods which was significantly lower than both SWS2 and SWS3. SDNN remained at pre-sleep levels until SWS3, and then significantly increased in REM1&2. There was a large drop in LF from pre-sleep to SWS1. As cycles progressed through the night, LF remains lower than awake but increases to awake like levels by REM2. RMSSD and HF were lowest in pre-sleep and increased significantly by SWS1 and remain high and stable across stages and cycles except during the REM3 period where RMSSD decreased. Conclusion: Our results demonstrate that there are considerable changes in the spectral analysis of cardiac function occurring during different sleep stages and between sleep cycles across the night. Hence, time of night and sleep stage need to be considered when reporting any HRV differences.

Differences in dentofacial morphology in children with sleep disordered breathing are detected with routine orthodontic records.

BACKGROUND: Residual snoring in children with obstructive sleep disordered breathing (SDB) may continue post-adenotonsillectomy. This study aims to identify baseline dentofacial differences in children with SDB using routine orthodontic records that might aid effective early intervention for the upper airway to prevent continued obstruction. METHODS: Children (6-16 years) with clinically diagnosed SDB from a paediatric Otolaryngology Clinic who required adenotonsillectomy were participants (n = 10). The control group (n = 9) comprised healthy non-snoring children from the community. Baseline overnight polysomnography (PSG), standardised frontal and right profile photographs and alginate impressions were taken of all children. Facial width, length, depth, convexity and mandibular position were measured from the photographs. The occlusion, arch width, arch depth, maxillary arch form, palatal height and volume were recorded from digitised dental models. Inter-group differences were compared. RESULTS: SDB patients had a significantly increased lower face height, maxillo-mandibular angle (1.73°; 95% CI 0.45-3.0) and a narrower maxillary arch in the upper posterior region. There was a trend towards a decreased palatal volume, increased posterior crossbite and Class II molar relationship. CONCLUSION: Dentofacial phenotypic differences between children with SDB and controls can be detected using facial photographs and dental models. Increased awareness of these features may help to identify children who to continue to snore post adenotonsillectomy.

Effect of adenotonsillectomy for childhood obstructive sleep apnea on nocturnal heart rate patterns.

Study Objectives: To assess the effect of adenotonsillectomy for relieving obstructive sleep apnea syndrome (OSAS) symptoms in children on cardiac autonomic modulation. Methods: In 354 children enrolled in the Childhood Adenotonsillectomy Trial, randomized to undergo either early adenotonsillectomy (eAT; N = 181) or a strategy of watchful waiting with supportive care (WWSC; N = 173), nocturnal heart rate control was analyzed during quiet, event-free sleep at baseline and at 7 months using overnight polysomnography (PSG). The relative frequency of patterns indicating monotonous changes in heart rate was quantified. Results: Children who underwent eAT demonstrated a significantly greater reduction in heart rate patterns postsurgery than the WWSC group. On assessing those heart rate patterns regarding normalization of clinical PSG, heart patterns were reduced to a similar level in both groups. In children whose AHI normalized spontaneously, heart rate patterns were already significantly less frequent at baseline, suggesting that upper airway obstruction was milder in this group at the outset. Conclusions: Adenotonsillectomy reduces monotonous heart rate patterns throughout quiet event-free sleep, reflecting a reduction in cardiac autonomic modulation. Heart rate pattern analysis may help quantifying the effect of OSAS on autonomic nervous system activity in children. Clinical Trial Registration: The study was registered at Clinicaltrials.gov (#NCT00560859).

Changes in growth and sleep across school nights, weekends and a winter holiday period in two Australian schools.

Studies suggest that there may be an association between sleep and growth; however, the relationship is not well understood. Changes in biology and external factors such as school schedule heavily impact the sleep of adolescents, during a critical phase for growth. This study assessed the changes in sleep across school days, weekends and school holidays, while also measuring height and weight changes, and self-reported alterations in food intake and physical activity. The impact of morningness-eveningness (M-E) on height change and weight gain was also investigated. In a sample of 63 adolescents (mean age = 13.13, SD = 0.33, 31 males) from two independent schools in South Australia, height and weight were measured weekly for 4 weeks prior to the school holidays and 4 weeks after the school holidays. Participants also completed a Morningness/Eveningness Scale and 7-day sleep, diet and physical activity diaries prior to, during and after the school holidays. Participants at one school had earlier wake times during the weekends than participants attending the other school, leading to a significantly shorter sleep duration on weekends for those participants. Regardless of school, sleep was significantly later and longer during the holidays (p < 0.001) and those with a stronger morning preference fell asleep (F18,36 = 3.4, p = 0.001) and woke (F18,44 = 2.0, p = 0.027) earlier than evening types. Growth rate was lower during the holiday weeks. For those attending the school with limited sleep in opportunities, growth after the holidays was lower for those with greater evening preference, whereas for those at the other school, growth was greater for those with greater evening preference. The increase in average weight from pre- to post-holidays was greater for those attending the school with limited opportunities to sleep longer. Participants reported greater food intake during the holidays compared to school days and greater physical activity levels on weekends compared to school days, and school days compared to holidays. Results suggest that time of day preference may impact growth, with evening types who cannot sleep in growing at a slower rate than evening types who can or morning types. This may be related to sleep restriction. Despite sleep being both later and longer during the school holidays, participants' growth slowed during the holiday period. It is possible that this may be a reflection of other behavioural changes in the holidays (increased food intake and reduced physical activity), as sleep timing during the school period was related to growth.

Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8 + T cells expressing TNFα and IFNγ.

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5-14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8+ cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO2 nadir was associated with an increased ascending aorta peak systolic velocity (r = - 0.48, p < 0.05). As well, both a lower SaO2 nadir and an increased ascending aorta peak systolic velocity were associated with higher SDSC Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep subscale scores but not the polysomnographic-derived Obstructive Apnea-Hypopnea Index. The finding of elevated ascending aortic peak systolic blood flow velocity and its association with increased inflammatory markers suggests that the profile of cardiovascular changes noted in adult SDB may also occur in children with mild SDB.

Altered Nocturnal Cardiovascular Control in Children With Sleep-Disordered Breathing.

Study objectives: To assess cardiovascular control during sleep in children with sleep-disordered breathing (SDB) and the effect of adenotonsillectomy in comparison to healthy nonsnoring children. Methods: Cardiorespiratory signals obtained from overnight polysomnographic recordings of 28 children with SDB and 34 healthy nonsnoring children were analyzed. We employed an autoregressive closed-loop model with heart period (RR) and pulse transit time (PTT) as outputs and respiration as an external input to obtain estimates of respiratory gain and baroreflex gain. Results: Mean and variability of PTT were increased in children with SDB across all stages of sleep. Low frequency power of RR and PTT were attenuated during non-rapid eye movement (REM) sleep. Baroreflex sensitivity was reduced in children with SDB in stage 2 sleep, while respiratory gain was increased in slow wave sleep. After adenotonsillectomy, these indices normalized in the SDB group attaining values comparable to those of healthy children. Conclusions: In children with mild-to-moderate SDB, vasomotor activity is increased and baroreflex sensitivity decreased during quiet, event-free non-REM sleep. Adenotonsillectomy appears to reverse this effect.

Relationship between Vascular Resistance and Sympathetic Nerve Fiber Density in Arterial Vessels in Children With Sleep Disordered Breathing.

BACKGROUND: Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling. Importantly, increased vascular sympathetic nerve fiber density and innervation in early life plays a key role in the development of early-onset hypertension in animal models. Examination of sympathetic nerve fiber density of the tonsillar arteries in children undergoing adenotonsillectomy for Sleep disordered breathing will address this question in humans. METHODS AND RESULTS: Thirteen children scheduled for adenotonsillectomy to treat sleep disordered breathing underwent pupillometry, polysomnography, flow-mediated dilation, resting brachial artery blood flow velocity (velocity time integral), and platelet aggregation. The dorsal lingual artery (tonsil) was stained and immunofluorescence techniques used to determine sympathetic nerve fiber density. Sympathetic nerve fiber density was correlated with increased resting velocity time integral (r=0.63; P<0.05) and a lower Neuronal Pupillary Index (r=-0.71, P<0.01), as well as a slower mean pupillary constriction velocity (mean, r=-0.64; P<0.05). A faster resting velocity time integral was associated with a slower peak pupillary constriction velocity (r=-0.77; P<0.01) and higher platelet aggregation to collagen antigen (r=0.64; P<0.05). Slower mean and peak pupillary constriction velocity were associated with higher platelet aggregation scores (P<0.05; P<0.01, respectively). CONCLUSIONS: These results indicate that sympathetic activity is associated with change in both the function and structure of systemic vasculature in children with sleep disordered breathing.

Adenotonsillectomy for childhood obstructive sleep apnoea reduces thoraco-abdominal asynchrony but spontaneous apnoea-hypopnoea index normalisation does not.

The efficacy of adenotonsillectomy for treating obstructive sleep apnoea syndrome (OSAS) in children has been established, but its precise effects on inspiratory effort are not well documented.In 353 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (n=182) or a strategy of watchful waiting with supportive care (WWSC) (n=171), thoraco-abdominal asynchrony (TAA) was analysed during quiet, non-apnoeic and non-hypopnoeic breathing during sleep at baseline and at 7 months using overnight polysomnography.Children who underwent early adenotonsillectomy demonstrated a reduction in TAA post-surgery while the WWSC arm showed no change. On assessing TAA with regard to normalisation of clinical polysomnography findings at follow-up, TAA was reduced in children who had surgical resolution of OSAS (based on apnoea-hypopnoea index), but not in children who displayed spontaneous normalisation of apnoea-hypopnoea index. In the latter group, TAA was inversely correlated with quality of life.We conclude that adenotonsillectomy reduces TAA during quiet sleep. Monitoring of instantaneous TAA may yield additional insight in the dynamic changes of inspiratory effort. In combination with traditional indices of obstruction, TAA may more accurately characterise the degree of sleep-disordered breathing in children.

The effect of adenotonsillectomy for childhood sleep apnoea on cardiorespiratory control.

The efficacy of adenotonsillectomy for relieving obstructive sleep apnoea symptoms in children has been firmly established, but its precise effects on cardiorespiratory control are poorly understood. In 375 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either adenotonsillectomy (n=194) or a strategy of watching waiting (n=181), respiratory rate, respiratory sinus arrhythmia and heart rate were analysed during quiet, non-apnoeic and non-hypopnoeic breathing throughout sleep at baseline and at 7 months using overnight polysomnography. Children who underwent early adenotonsillectomy demonstrated an increase in respiratory rate post-surgery while the watchful waiting group showed no change. Heart rate and respiratory sinus arrhythmia were comparable between both arms. On assessing cardiorespiratory variables with regard to normalisation of clinical polysomnography findings during follow-up, heart rate was reduced in children who had resolution of obstructive sleep apnoea syndrome, while no differences in their respiratory rate or respiratory sinus arrhythmia were observed. Adenotonsillectomy for obstructive sleep apnoea increases baseline respiratory rate during sleep. Normalisation of apnoea-hypopnoea index, spontaneously or via surgery, lowers heart rate. Considering the small average effect size, the clinical significance is uncertain.

Prenatal Fish Oil Supplementation and Allergy: 6-Year Follow-up of a Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Evidence from randomized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease characterized by an immunoglobulin E (IgE) response. We aimed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy. METHODS: Six-year follow-up of children (n = 706) with a family history of allergic disease from the Docosahexaenoic Acid to Optimize Mother Infant Outcome (DOMInO) trial. Women were randomly allocated to receive n-3 LCPUFA-rich fish oil capsules (800 mg/d docosahexaenoic acid DHA and 100mg/d eicosapentaenoic acid) or vegetable oil capsules (without n-3 LCPUFA). Allergic disease symptoms including eczema, wheeze, rhinitis, and rhino-conjunctivitis, were assessed using the International Study of Asthma and Allergies in Childhood questionnaire and sensitization to allergens was measured by skin prick test. RESULTS: There was no difference in the percentage of children with any IgE-associated allergic disease between the n-3 LCPUFA and control groups (116/367 [31.5%] vs 106/336 [31.5%]; adjusted relative risk, 1.04; 95% confidence interval, 0.82-1.33; P = .73). There was a reduction in the percentage of children sensitized to house dust mite Dermatophagoides farinae (49/367 [13.4%] vs 68/336 [20.3%]; adjusted relative risk, 0.67, 95% confidence interval, 0.44-1.00; P = .0495). CONCLUSIONS: Prenatal n-3 LCPUFA supplementation did not reduce IgE-associated allergic disease at 6 years of age. Secondary outcomes were suggestive of a protective effect of the intervention on the incidence of D. farinae sensitization.

Omega-3 long-chain PUFA intake during pregnancy and allergic disease outcomes in the offspring: a systematic review and meta-analysis of observational studies and randomized controlled trials.

BACKGROUND: There is some evidence that increased maternal intake of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy may reduce the incidence of immunoglobulin E (IgE)-mediated allergic disease. OBJECTIVE: We aimed to evaluate prenatal n-3 LC-PUFA dietary exposure in observational studies and n-3 LC-PUFA supplementation in randomized controlled trials (RCTs) on outcomes of IgE-mediated allergic disease. DESIGN: We conducted searches of the Cochrane Central Register of Controlled Trials, PubMed, Ovid MEDLINE, EMBASE, CINAHL, SCOPUS, and Web of Science to 30 July 2015. We included prospective cohort studies that showed an association between maternal fish or n-3 LC-PUFA intake during pregnancy and RCTs with a prenatal intervention to modify maternal n-3 LC-PUFA intake and outcomes of allergic disease (eczema, rhino-conjunctivitis, asthma) or sensitization in the offspring. RESULTS: A total of 13 publications from 10 prospective cohort studies and 7 publications representing 5 unique RCTs were included. Three RCTs were combined in a meta-analysis for selected outcomes. Nine of 13 observational study publications and 5 of 7 publications from RCTs found a protective association between increased prenatal n-3 LC-PUFA or fish intake and incidence of allergic disease symptoms in the child. Meta-analysis was limited because of the heterogeneity of the RCTs. Pooled results showed a significant reduction in the incidence of "atopic eczema," "any positive SPT [skin-prick test]," "sensitization to egg," and "sensitization to any food" in the first 12 mo of life [RRs (95% CIs): 0.53 (0.35, 0.81), P = 0.004; 0.68 (0.52-0.89), P = 0.006; 0.55 (0.39-0.76), P = 0.0004; and 0.59 (0.46, 0.76), P < 0.0001, respectively]. CONCLUSIONS: Our systematic review and meta-analysis was suggestive of benefits of increased n-3 LC-PUFAs in the maternal diet and outcomes of childhood allergic disease. However, due to the inconsistency in results, the hypothesis linking maternal n-3 LC-PUFA intake to childhood allergic disease cannot unequivocally be confirmed or rejected.

Delayed brachial artery dilation response and increased resting blood flow velocity in young children with mild sleep-disordered breathing.

AIM: This study aimed to evaluate whether the vascular dysfunction perceived in adults with sleep-disordered breathing (SDB) was also evident in children with snoring referred for evaluation of clinically suspected SDB. OBJECTIVES: This study compared flow-mediated dilatation (FMD), measured at the brachial artery, at rest and during hyperaemic stress between children who snore [n = 23; mean standard deviation (SD) age = 7.51 (1.3) years] and healthy, non-snoring children [n = 11; age = 8.0 (1.3) years]. METHODS: Children with suspected obstructive sleep apnoea (OSA) and healthy non-snoring controls underwent overnight polysomnography (PSG). Using standard techniques, non-invasive FMD and brachial arterial blood flow velocity during rest and hyperaemia were subsequently measured by ultrasound imaging MEASUREMENTS: Resting and hyperaemic velocity time integral (area under the curve of mean systolic velocity × ejection time), maximal dilation response (highest percentage difference from baseline diameter) and the time taken to reach maximal dilation were calculated. RESULTS: Children awaiting adenotonsillectomy compared to healthy non-snoring control children had higher velocity time integrals at rest (14 ± 3 m vs. 20 ± 8 m, p < 0.01) and during hyperaemic stress (56 ± 6m vs. 63 ± 13m, p < 0.01) despite having only mild SDB on polysomnographic assessment. Lower nadir oxygen saturation values during non-rapid eye movement sleep were negatively associated with higher resting (r = -0.58, p <0.001) and hyperaemic (r = -0.36, p < 0.05) velocity time integrals. Maximal FMD dilatation response was not significantly different between snoring and non-snoring groups, but the estimated time to reach maximal dilation was significantly delayed in children who snored (60.7 ± 28.4 vs. 39.2 ± 13.2 s, p < 0.05). CONCLUSIONS: Children with mild SDB showed increased blood flow velocity at rest and during hyperaemic stress suggesting altered cardiovascular and haemodynamic function. The delay in time to maximal vessel dilatation in children who snored also suggests possible reduced vascular compliance in response to hyperaemic sheer stress. Mild SDB appears to alter the peripheral vascular response in young children. The long-term vascular implications of these changes in the growing child are unknown and warrant further investigation.

Effect of respiration on heartbeat-evoked potentials during sleep in children with sleep-disordered breathing.

OBJECTIVE: Heartbeat-evoked potentials (HEPs) in electroencephalogram (EEG) provide a quantitative measure of cardiac interoception during sleep. We previously reported reduced HEPs in children with sleep-disordered breathing (SDB), indicative of attenuated cardiac information processing. The objective of this study was to investigate the link between HEP and respiration. PATIENTS/METHODS: From the overnight polysomnograms of 40 healthy children and 40 children with SDB, we measured HEPs during epochs of stage 2, slow-wave and rapid eye movement (REM) sleep free of abnormal respiratory events. HEPs were analysed with respect to respiratory phase. RESULTS: We observed a marked association between respiratory phase and HEP in children with SDB during REM sleep, but not in normal children. In children with SDB, HEP waveforms were attenuated during expiration compared to inspiration. Following adenotonsillectomy, expiratory HEP peak amplitude increased in the SDB children and was no longer different from those of normal children. CONCLUSIONS: The expiratory phase of respiration is primarily associated with attenuated cardiac information processing in children with SDB, establishing a pathophysiological link between breathing and HEP attenuation.