Enuresis associated with sleep disordered breathing in children with sickle cell anemia.

PURPOSE: Enuresis and sleep disordered breathing are common among children with sickle cell anemia. We evaluated whether enuresis is associated with sleep disordered breathing in children with sickle cell anemia. MATERIALS AND METHODS: Baseline data were used from a multicenter prospective cohort study of 221 unselected children with sickle cell anemia. A questionnaire was used to evaluate, by parental report during the previous month, the presence of enuresis and its severity. Overnight polysomnography was used to determine the presence of sleep disordered breathing by the number of obstructive apneas and/or hypopneas per hour of sleep. Logistic and ordinal regression models were used to evaluate the association of sleep disordered breathing and enuresis. RESULTS: The mean age of participants was 10.1 years (median 10.0, range 4 to 19). Enuresis occurred in 38.9% of participants and was significantly associated with an obstructive apnea-hypopnea index of 2 or more per hour after adjusting for age and gender (OR 2.19; 95% CI 1.09, 4.40; p = 0.03). Enuresis severity was associated with obstructive apneas and hypopneas with 3% or more desaturation 2 or more times per hour with and without habitual snoring (OR 3.23; 95% CI 1.53, 6.81; p = 0.001 and OR 2.07; 95% CI 1.09, 3.92; p = 0.03, respectively). CONCLUSIONS: In this unselected group of children with sickle cell anemia, sleep disordered breathing was associated with enuresis. Results of this study support that children with sickle cell anemia who present with enuresis should be evaluated by a pulmonologist for sleep disordered breathing.

Observational study to define reference ranges for the 3% oxygen desaturation index during sleep in healthy children under 12 years using oximetry motion-resistant technology.

OBJECTIVE: To define reference ranges for the 3% oxygen desaturation index (DI3) in healthy children under 12 years old during sleep. DESIGN: Observational. SETTING: Home. SUBJECTS: Healthy children aged 6 months to 12 years of age. INTERVENTION: Nocturnal pulse oximetry at home. Parents documented sleep times. Visi-Download software (Stowood Scientific) analysed data with artefact and wake periods removed. MAIN OUTCOME MEASURES: The following oximetry parameters used in the assessment of sleep-disordered breathing conditions were measured: 3% (DI3) and 4% (DI4) oxygen desaturation indices-the number of times per hour where the oxygen saturation falls by at least 3% or 4% from baseline, mean saturations (SAT50), minimum saturations (SATmin), delta index 12 s (DI12s), and percentage time with saturations below 92% and 90%. RESULTS: Seventy-nine children underwent nocturnal home pulse oximetry, from which there were 66 studies suitable for analysis. The median values for DI3 and DI4 were 2.58 (95% CI 1.96 to 3.10) and 0.92 (95% CI 0.73 to 1.15), respectively. The 95th and 97.5th centiles for DI3 were 6.43 and 7.06, respectively, which inform our cut-off value for normality. The mean values for SAT50 and SATmin were 97.57% (95% CI 97.38% to 97.76%) and 91.09% (95% CI 90.32% to 91.86%), respectively. CONCLUSION: In children aged 6 months to 12 years, we define normality of the 3% oxygen desaturation index as <7 using standalone, motion-resistant pulse oximeters with short averaging times.

Cardiorespiratory sleep studies at home: experience in research and clinical cohorts.

OBJECTIVE: To evaluate the success rates of home cardiorespiratory polygraphy in children under investigation for sleep-disordered breathing and parent perspectives on equipment use at home. DESIGN: Prospective observational study. SETTING: Sheffield, Evelina London and Southampton Children's Hospitals. PATIENTS: Data are reported for 194 research participants with Down syndrome, aged 0.5-5.9 years across the three centres and 61 clinical patients aged 0.4-19.5 years from one centre, all of whom had home cardiorespiratory polygraphy including respiratory movements, nasal pressure flow, pulse oximetry, body position and motion. MAIN OUTCOME MEASURES: Percentage of home cardiorespiratory studies successfully acquiring ≥4 hours of artefact-free data at the first attempt. Parental report of ease of use of equipment and preparedness to repeat home diagnostics in the future. RESULTS: 143/194 (74%; 95% CI 67% to 79%) of research participants and 50/61 (82%; 95% CI 71% to 90%) of clinical patients had successful home cardiorespiratory polygraphy at the first attempt. Some children required multiple attempts to achieve a successful study. Overall, this equated to 1.3 studies per research participant and 1.2 studies per clinical child. The median artefact-free sleep time for successful research studies was 515 min (range 261-673) and for clinical studies 442 min (range 291-583). 84% of research and 87% of clinical parents expressed willingness to repeat home cardiorespiratory polygraphy in the future. 67% of research parents found the equipment 'easy or okay' to use, while 64% of clinical parents reported it as 'easy' or 'very easy'. CONCLUSIONS: Home cardiorespiratory polygraphy offers an acceptable approach to the assessment of sleep-disordered breathing in children.

Prevention of Morbidity in Sickle Cell Disease (POMS2a)-overnight auto-adjusting continuous positive airway pressure compared with nocturnal oxygen therapy: a randomised crossover pilot study examining patient preference and safety in adults and children.

DESIGN: This randomised crossover trial compared nocturnal auto-adjusting continuous positive airway pressure (APAP) and nocturnal oxygen therapy (NOT) in adults and children with sickle cell anaemia, with patient acceptability as the primary outcome. Secondary outcomes included pulmonary physiology (adults), safety, and daily pain during interventions and washout documented using tablet technology. METHODS: Inclusion criteria were age > 8 years and the ability to use an iPad to collect daily pain data. Trial participation was 4 weeks; week 1 involved baseline data collection and week 3 was a washout between interventions, which were administered for 7 days each during weeks 2 and 4 in a randomised order. Qualitative interviews were transcribed verbatim and analysed for content using a funnelling technique, starting generally and then gaining more detailed information on the experience of both interventions. Safety data included routine haematology and median pain days between each period. Missing pain day values were replaced using multiple imputation. RESULTS: Ten adults (three female, median age 30.2 years, range 18-51.5 years) and eleven children (five female, median age 12 years, range 8.7-16.9 years) enrolled. Nine adults and seven children completed interviews. Qualitative data revealed that the APAP machine was smaller, easier to handle, and less noisy. Of 16 participants, 10 preferred APAP (62.5%, 95% confidence interval (CI) 38.6-81.5%). Haemoglobin decreased from baseline on APAP and NOT (mean difference -3.2 g/L (95% CI -6.0 to -0.2 g/L) and -2.5 g/L (95% CI -4.6 to 0.3 g/L), respectively), but there was no significant difference between interventions (NOT versus APAP, 1.1 (-1.2 to 3.6)). Pulmonary function changed little. Compared with baseline, there were significant decreases in the median number of pain days (1.58 for APAP and 1.71 for NOT) but no significant difference comparing washout with baseline. After adjustment for carry-over and period effects, there was a non-significant median difference of 0.143 (95% CI -0.116 to 0.401) days additional pain with APAP compared with NOT. CONCLUSION: In view of the point estimate of patient preference for APAP, and no difference in haematology or pulmonary function or evidence that pain was worse during or in washout after APAP, it was decided to proceed with a Phase II trial of 6 months APAP versus standard care with further safety monitoring for bone marrow suppression and pain. TRIAL REGISTRATION: ISRCTN46078697 . Registered on 18 July 2014.

A cohort study reporting normal oximetry values in healthy infants under 4 months of age using Masimo technology.

OBJECTIVE: To determine sleeping saturation indices in healthy infants using a modern pulse oximeter with motion artefact extraction technology. DESIGN: Prospective cohort. SETTING: Home. SUBJECTS: Healthy term infants. INTERVENTION: Nocturnal pulse oximetry at home at 1 month of age (Recording 1) and repeated at age 3-4 months (Recording 2). Parents documented sleep times. Visi-Download software (Stowood Scientific) analysed data with artefact and wake periods removed. MAIN OUTCOME MEASURES: Saturations (SAT50), desaturation index >4% (DI4) and >3% (DI3) from baseline/hour, delta index 12 s (DI12s), minimum saturations (SATmin), percentage time with saturations below 90% and 92%. RESULTS: Forty-five babies were studied at 1 month and 38 babies at 3-4 months. Mean (CI) SAT50, DI4, DI3, DI12s and SATmin (CI) were 97.05 (96.59 to 97.52), 16.16 (13.72 to 18.59), 25.41 (22.00 to 28.82), 0.96 (0.88 to 1.04) and 80.4% (78.8% to 82.0%) at 1 month, respectively, and 97.65 (97.19 to 98.12), 8.12 (6.46 to 9.77), 13.92 (11.38 to 16.47), 0.72 (0.65 to 0.78) and 84.7% (83.3% to 86.1%) at 3-4 months. Median (CI) percentage times with saturations below 90% and 92% were 0.39 (0.26 to 0.55) and 0.82 (0.60 to 1.23), respectively, at 1 month and 0.11 (0.06 to 0.20) and 0.25 (0.17 to 0.44) at 3-4 months. For paired samples (n=32) DI4 (P=0.006), DI3 (P=0.03), DI12s (P=0.001), percentage time with saturations below 90% (P=0.001) and 92% (P=0.000) all fell significantly and SATmin (P=0.004) rose between the two recordings. CONCLUSION: Desaturation indices are substantially higher in young infants than older children where a DI4 over 4 is considered abnormal. These decrease by 3-4 months of age but still remain elevated compared with older children.

Home oximetry to screen for obstructive sleep apnoea in Down syndrome.

OBJECTIVE: Children with Down syndrome are at high risk of obstructive sleep apnoea (OSA) and screening is recommended. Diagnosis of OSA should be confirmed with multichannel sleep studies. We aimed to determine whether home pulse oximetry (HPO) discriminates children at high risk of OSA, who need further diagnostic multichannel sleep studies. DESIGN: Cross-sectional prospective study in a training sample recruited through three UK centres. Validation sample used single-centre retrospective analysis of clinical data. PATIENTS: Children with Down syndrome aged 0.5-6 years. INTERVENTION: Diagnostic multichannel sleep study and HPO. MAIN OUTCOME MEASURES: Sensitivity and specificity of HPO to predict moderate-to-severe OSA. RESULTS: 161/202 children with Down syndrome met quality criteria for inclusion and 25 had OSA. In this training sample, the best HPO parameter predictors of OSA were the delta 12 s index >0.555 (sensitivity 92%, specificity 65%) and 3% oxyhaemoglobin (SpO2) desaturation index (3% ODI)>6.15 dips/hour (sensitivity 92%, specificity 63%). Combining variables (delta 12 s index, 3% ODI, mean and minimum SpO2) achieved sensitivity of 96% but reduced specificity to 52%. All predictors retained or improved sensitivity in a clinical validation sample of 50 children with variable loss of specificity, best overall was the delta 12 s index, a measure of baseline SpO2 variability (sensitivity 92%; specificity 63%). CONCLUSIONS: HPO screening could halve the number of children with Down syndrome needing multichannel sleep studies and reduce the burden on children, families and health services alike. This approach offers a practical universal screening approach for OSA in Down syndrome that is accessible to the non-specialist paediatrician.

Prevalence and predictors of obstructive sleep apnoea in young children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) are vulnerable to obstructive sleep apnoea (OSA) because of their unique craniofacial anatomy and hypotonia. Understanding the predictors of OSA in DS may enable targeted screening. METHODS: Children with DS (n = 202) aged from six months to below six years (110 boys) were recruited from three UK children's hospitals. The clinical assessment included height, weight and tonsillar size. The parents either set up cardiorespiratory polygraphy at home or chose laboratory studies. Studies with less than four hours of interpretable data were repeated where possible. American Academy of Sleep Medicine (AASM) 2012 scoring criteria were used to derive an obstructive apnoea/hypopnoea index (OAHI). Predictors of moderate to severe OSA were examined. RESULTS: In total, 188/202 (93%) participants were successfully studied. Of these, 169 studies were completed at home and 19 in a sleep laboratory. Moderate to severe OSA, defined by an OAHI of >5/h, was found in 14% and mild to moderate OSA (1/h≥OAHI <5/h) was found in 59% of the children. Male gender and habitual snoring predicted OSA but did not have independent predictive power in the presence of the other factors. Age in months, body mass index (BMI) centile and tonsillar size did not predict OSA. CONCLUSIONS: Moderate to severe OSA is common in very young children with DS. Examination of tonsillar size did not predict OSA severity. Population-based screening for OSA is recommended in these children, and domiciliary cardiorespiratory polygraphy is an acceptable screening approach. Further research is required to understand the natural history, associated morbidity, optimal screening methodology and treatment modality for OSA in these children.

Obstructive sleep apnea and sickle cell anemia.

OBJECTIVE: To ascertain the prevalence of and risk factors for obstructive sleep apnea syndrome (OSAS) in children with sickle cell anemia (SCA). METHODS: Cross-sectional baseline data were analyzed from the Sleep and Asthma Cohort Study, a multicenter prospective study designed to evaluate the contribution of sleep and breathing abnormalities to SCA-related morbidity in children ages 4 to 18 years, unselected for OSAS symptoms or asthma. Multivariable logistic regression assessed the relationships between OSAS status on the basis of overnight in-laboratory polysomnography and putative risk factors obtained from questionnaires and direct measurements. RESULTS: Participants included 243 children with a median age of 10 years; 50% were boys, 99% were of African heritage, and 95% were homozygous for ß(S) hemoglobin. OSAS, defined by obstructive apnea hypopnea indices, was present in 100 (41%) or 25 (10%) children at cutpoints of ≥1 or ≥5, respectively. In univariate analyses, OSAS was associated with higher levels of habitual snoring, lower waking pulse oxygen saturation (Spo2), reduced lung function, less caretaker education, and non-preterm birth. Lower sleep-related Spo2 metrics were also associated with higher obstructive apnea hypopnea indices. In multivariable analyses, habitual snoring and lower waking Spo2 remained risk factors for OSAS in children with SCA. CONCLUSIONS: The prevalence of OSAS in children with SCA is higher than in the general pediatric population. Habitual snoring and lower waking Spo2 values, data easily obtained in routine care, were the strongest OSAS risk factors. Because OSAS is a treatable condition with adverse health outcomes, greater efforts are needed to screen, diagnose, and treat OSAS in this high-risk, vulnerable population.

The Young Everest Study: preliminary report of changes in sleep and cerebral blood flow velocity during slow ascent to altitude in unacclimatised children.

BACKGROUND: Cerebral blood flow velocity (CBFV) and sleep physiology in healthy children exposed to hypoxia and hypocarbia are under-researched. AIM: To investigate associations between sleep variables, daytime end-tidal carbon dioxide (EtCO2) and CBFV in children during high-altitude ascent. METHODS: Vital signs, overnight cardiorespiratory sleep studies and transcranial Doppler were undertaken in nine children (aged 6-13 years) at low altitude (130 m), and then at moderate (1300 m) and high (3500 m) altitude during a 5-day ascent. RESULTS: Daytime (130 m: 98%; 3500 m: 90%, p=0.004) and mean (130 m: 97%, 1300 m: 94%, 3500: 87%, p=0.0005) and minimum (130 m: 92%, 1300 m: 84%, 3500 m: 79%, p=0.0005) overnight pulse oximetry oxyhaemoglobin saturation decreased, and the number of central apnoeas increased at altitude (130 m: 0.2/h, 1300 m: 1.2/h, 3500 m: 3.5/h, p=0.2), correlating inversely with EtCO2 (R(2) 130 m: 0.78; 3500 m: 0.45). Periodic breathing occurred for median (IQR) 0.0 (0; 0.3)% (130 m) and 0.2 (0; 1.2)% (3500 m) of total sleep time. At 3500 m compared with 130 m, there were increases in middle (MCA) (mean (SD) left 29.2 (42.3)%, p=0.053; right 9.9 (12)%, p=0.037) and anterior cerebral (ACA) (left 65.2 (69)%, p=0.024; right 109 (179)%; p=0.025) but not posterior or basilar CBFV. The right MCA CBFV increase at 3500 m was predicted by baseline CBFV and change in daytime SpO2 and EtCO2 at 3500 m (R(2) 0.92); these associations were not seen on the left. CONCLUSIONS: This preliminary report suggests that sleep physiology is disturbed in children even with slow ascent to altitude. The regional variations in CBFV and their association with hypoxia and hypocapnia require further investigation.