Longitudinal pilot study of oxygen saturation indices in healthy preterm infants.

BACKGROUND: This study aimed to determine patterns of nocturnal pulse oximetry indices in moderate to late preterm infants, and investigate the relationship between oxygen desaturations, the apnoea hypopnoea index, and both corrected gestational and postnatal age. METHODS: 21 healthy infants born at 32 + 0 - 36 + 6 weeks gestation underwent serial nocturnal pulse oximetry studies and respiratory polygraphy studies until 40 weeks corrected gestational age (CGA). The main outcome measures were number of >3% oxygen desaturations/hour (ODI3), mean oxygen saturations, and number of apnoeas and hypopnoeas/hour. RESULTS: Median ODI3 increased between weeks 1 and 3 from 49.9 to 85.4/hour (p = 0.017). Mean oxygen saturations reached a corresponding nadir of 96.0% in week 3, then increased to 96.8% in week 6 (p = 0.019). Mixed effects modelling demonstrated that ODI3 and mean saturations were influenced by postnatal age but not CGA (p < 0.05). Desaturations frequently occurred without an apnoea or hypopnoea. CONCLUSION: ODI3 rises then falls during the first 8 weeks of life in moderate to late preterm infants, independently of CGA. These interesting preliminary results highlight the importance of further serial data collection to generate age-specific normal ranges, and develop a better understanding of respiratory control in preterm infants. IMPACT: The frequency of >3% oxygen desaturations (ODI3) in healthy moderate to late preterm infants rises then falls after birth, peaking in postnatal week 3. There is a corresponding nadir in mean saturations. There were significant non-linear relationships between ODI3/mean saturations and postnatal age, but not corrected gestational age. The majority of brief oxygen desaturations occurred without an apnoea or hypopnoea. Normal ranges for oxygen saturation indices are not known in this population. These results demonstrate the need for further serial data collection to generate age-specific normal ranges and inform oxygen prescribing guidelines.

Use of pulse oximetry as an investigative test for paediatric respiratory sleep disorders.

The article covers the following elements: practical and technological considerations for optimising data collection and output; reference ranges for oximetry parameters across the ages; things to consider when interpreting a pulse oximetry study (eg, sleep/wake times); the ability of pulse oximetry to predict obstructive sleep apnoea; using oximetry as a screening tool for sleep disordered breathing in children with Down syndrome; things to consider when setting up a home oximetry service; and a case of an infant being weaned from oxygen using pulse oximetry studies.

Weaning oxygen in infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease commonly seen in preterm infants as the sequelae following respiratory distress syndrome. The management of evolving BPD aims to minimise lung injury and prevent the impact of hypoxia and hyperoxia. Proposed morbidities include respiratory instability, pulmonary hypertension, suboptimal growth, altered cerebral oxygenation and long-term neurodevelopmental impairment. The ongoing management and associated morbidity present a significant burden for carers and healthcare systems. Long-term oxygen therapy may be required for variable duration, though there is a lack of consensus and wide variation in practise when weaning supplemental oxygen. Furthermore, a shift in care towards earlier discharge and community care underlines the importance of a structured discharge and weaning process that eliminates the potential risks associated with hypoxia and hyperoxia. This review article describes recent evidence outlining oxygen saturation reference ranges in young infants, on which structured guidance can be based.

PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia.

Symptoms of primary ciliary dyskinesia (PCD) are nonspecific and guidance on whom to refer for testing is limited. Diagnostic tests for PCD are highly specialised, requiring expensive equipment and experienced PCD scientists. This study aims to develop a practical clinical diagnostic tool to identify patients requiring testing.Patients consecutively referred for testing were studied. Information readily obtained from patient history was correlated with diagnostic outcome. Using logistic regression, the predictive performance of the best model was tested by receiver operating characteristic curve analyses. The model was simplified into a practical tool (PICADAR) and externally validated in a second diagnostic centre.Of 641 referrals with a definitive diagnostic outcome, 75 (12%) were positive. PICADAR applies to patients with persistent wet cough and has seven predictive parameters: full-term gestation, neonatal chest symptoms, neonatal intensive care admittance, chronic rhinitis, ear symptoms, situs inversus and congenital cardiac defect. Sensitivity and specificity of the tool were 0.90 and 0.75 for a cut-off score of 5 points. Area under the curve for the internally and externally validated tool was 0.91 and 0.87, respectively.PICADAR represents a simple diagnostic clinical prediction rule with good accuracy and validity, ready for testing in respiratory centres referring to PCD centres.

Accuracy of diagnostic testing in primary ciliary dyskinesia.

Diagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

Validation of a portable nitric oxide analyzer for screening in primary ciliary dyskinesias.

BACKGROUND: Nasal nitric oxide (nNO) levels are very low in primary ciliary dyskinesia (PCD) and it is used as a screening test. METHODS: We assessed the reliability and usability of a hand-held analyser in comparison to a stationary nitric oxide (NO) analyser in 50 participants (15 healthy, 13 PCD, 22 other respiratory diseases; age 6-79 years). Nasal NO was measured using a stationary NO analyser during a breath-holding maneuver, and using a hand-held analyser during tidal breathing, sampling at 2 ml/sec or 5 ml/sec. The three methods were compared for their specificity and sensitivity as a screen for PCD, their success rate in different age groups, within subject repeatability and acceptability. Correlation between methods was assessed. RESULTS: Valid nNO measurements were obtained in 94% of participants using the stationary analyser, 96% using the hand-held analyser at 5 ml/sec and 76% at 2 ml/sec. The hand-held device at 5 ml/sec had excellent sensitivity and specificity as a screening test for PCD during tidal breathing (cut-off of 30 nL/min,100% sensitivity, >95% specificity). The cut-off using the stationary analyser during breath-hold was 38 nL/min (100% sensitivity, 95% specificity). The stationary and hand-held analyser (5 ml/sec) showed reasonable within-subject repeatability(% coefficient of variation = 15). CONCLUSION: The hand-held NO analyser provides a promising screening tool for PCD.

Role of overnight oximetry in assessing the severity of obstructive sleep apnoea in typically developing children: a multicentre study.

BACKGROUND AND OBJECTIVE: Cardiorespiratory polygraphy (CRP) is the predominant technology used to diagnose obstructive sleep apnoea (OSA) in tertiary centres in the UK. Nocturnal pulse oximetry (NPO) is, however, cheaper and more accessible. This study evaluated the ability of NPO indices to predict OSA in typically developing (TD) children. METHODS: Indices from simultaneous NPO and CRP recordings were compared in TD children (aged 1-16 years) referred to evaluate OSA in three tertiary centres. OSA was defined as an obstructive apnoea-hypopnoea index (OAHI) ≥1 event/hour. Receiver operating characteristic curves assessed the diagnostic accuracy of NPO indices including ODI3 (3% Oxygen Desaturation Index, ODI4 (4% Oxygen Desaturation Index), delta 12 s index and minimum oxygen saturation. Two-by-two tables were generated to determine the sensitivities and specificities of whole number cut-off values for predicting OAHIs ≥1, 5 and 10 events/hour. RESULTS: Recordings from 322 TD children, 197 male (61.2%), median age 4.9 years (range 1.1-15.6), were reviewed. OAHI was ≥1/hour in 144 (44.7%), ≥5/hour in 61 (18.9%) and ≥10/hour in 28 (8.7%) cases. ODI3 and ODI4 had the best diagnostic accuracy. ODI3 ≥7/hour and ODI4 ≥4/hour predicted OSA in TD children with sensitivities/specificities of 57.6%/85.4% and 46.2%/91.6%, respectively. ODI3 ≥8/hour was the best predictor of OAHI ≥5/hour (sensitivity 82.0%, specificity 84.3%). CONCLUSION: Raised ODI3 and ODI4 predict OSA in TD children with high specificity but variable sensitivity. NPO may be an alternative to diagnose moderate-severe OSA if access to CRP is limited. Low sensitivities to detect mild OSA mean that confirmatory CRP is needed if NPO is normal.

Recent advances in paediatric sleep disordered breathing.

This article reviews the latest evidence pertaining to childhood sleep disordered breathing (SDB), which is associated with negative neurobehavioural, cardiovascular and growth outcomes. Polysomnography is the accepted gold standard for diagnosing SDB but is expensive and limited to specialist centres. Simpler tests such as cardiorespiratory polygraphy and pulse oximetry are probably sufficient for diagnosing obstructive sleep apnoea (OSA) in typically developing children, and new data-processing techniques may improve their accuracy. Adenotonsillectomy is the first-line treatment for OSA, with recent evidence showing that intracapsular tonsillectomy results in lower rates of adverse events than traditional techniques. Anti-inflammatory medication and positive airway pressure respiratory support are not always suitable or successful, although weight loss and hypoglossal nerve stimulation may help in select comorbid conditions. Educational aims: To understand the clinical impact of childhood sleep disordered breathing (SDB).To understand that, while sleep laboratory polysomnography has been the gold standard for diagnosis of SDB, other diagnostic techniques exist with their own benefits and limitations.To recognise that adenotonsillectomy and positive pressure respiratory support are the mainstays of treating childhood SDB, but different approaches may be indicated in certain patient groups.

Rituximab therapy in ROHHAD(NET) syndrome.

OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation, and neural-crest tumour (ROHHAD(NET)) is a rare syndrome presenting in early childhood associated with high morbidity and mortality. There is no specific diagnostic biomarker and diagnosis is based on clinical features. An autoimmune origin has been postulated. CASE PRESENTATION: Management is largely supportive. We report a case of a five-year old female who presented in respiratory arrest after 6-months of rapid weight gain. She had central hypoventilation, central diabetes insipidus, growth hormone deficiency and hyperprolactinaemia. She displayed elevated interleukin-6 levels on cytokine serology which normalised after rituximab treatment. After rituximab treatment, her weight reduced significantly from greatly above the 99.6th to the 50th centile in 12 months. CONCLUSIONS: This response possibly reflects an underlying, immune-inflammatory pathology driving excess adiposity in this condition. Potentially, other aspects of ROHHAD(NET) may be mediated through autoimmune dysregulation in which case rituximab may provide benefits for prognosis and survival.

Characteristics and outcome of infants with bronchopulmonary dysplasia established on long-term ventilation from neonatal intensive care.

INTRODUCTION: Ex-preterm infants with severe bronchopulmonary dysplasia (BPD) sometimes require long-term ventilation (LTV) to facilitate weaning from respiratory support. There are however limited data characterizing this cohort. We aim to describe the background characteristics, neonatal comorbidities, characteristics at the initiation of ventilation, and outcomes of neonatal unit graduates with BPD established on LTV. METHODS: A retrospective cohort study of infants born <32 weeks gestation with BPD referred to a regional LTV service between January 2015 and December 2020. RESULTS: Twenty-five infants were referred during the study period. Median birth gestation was 26 + 1 weeks (24 + 0-30 + 4) and birth weight 645 g (430-1485). At 36 weeks postmenstrual age (PMA), median FiO2 was 0.45 (0.24-0.80) and one-quarter of infants remained on invasive ventilation. Twenty (80%) infants were established on noninvasive ventilation (NIV), with the smallest weighing 2085 g, and five (20%) required tracheostomy invasive ventilation (TIV). At initiation of NIV/TIV, median PMA was 41 + 1 weeks and median FiO2 0.40 (0.29-0.80). Infants established on TIV spent almost five times longer in hospital before discharge compared to those on NIV (p = 0.003). By March 2022, 18 (72%) infants had discontinued ventilation, spending a median total time of 113 days (18-1792) on ventilation. CONCLUSION: Due to advances in interfaces, headgear, and ventilator technology, NIV is an attractive and practically achievable option for infants with severe BPD as small as 2 kg. Initiation and weaning should take place in a facility with the required multidisciplinary expertize.

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.

Study protocol for randomised clinical trial comparing the effectiveness of side-lying sleep positioning to back-lying at reducing oxygen desaturation resulting from obstructive sleep apnoea in infants with cleft palate (SLUMBRS2).

INTRODUCTION: The craniofacial abnormalities found in infants with cleft palate (CP) decrease their airway patency and increase their risk of obstructive sleep apnoea (OSA). We hypothesise that optimising sleep position in infants with CP may improve airway patency and offer a 'low-cost, high-impact' intervention to prevent the negative impacts of OSA. Because cleft centres give inconsistent advice about sleep position: some recommend back-lying and others side-lying, we will compare these in a randomised controlled trial. METHODS AND ANALYSIS: The aim is to determine the clinical effectiveness of side-lying as compared with back-lying sleep positioning in terms of reducing oxygen desaturation resulting from OSA in 244 infants aged 3-5 weeks of age, diagnosed with an isolated CP in/by UK cleft centres. Primary outcome is the 4% Oxygen Desaturation Index measured using pulse oximetry during sleep. RESEARCH PLAN: 1. Multicentre randomised controlled trial of side-lying compared with back-lying sleep positioning in reducing oxygen desaturation resulting from OSA in infants with CP at one month of age. 2. Internal pilot questionnaire-based study to support parents and clinicians regarding study participation, seeking to identify and address any barriers to recruitment. Monitoring data from the internal pilot will be used in the final analysis. 3. Co-development of new UK recommendations with Cleft Lip and Palate Association (CLAPA) regarding sleep position for infants with CP. ETHICS AND DISSEMINATION: The study protocol has received the favourable opinion of the West Midlands-South Birmingham Research Ethics Committee. Study results will be published on affiliated webpages and in peer-reviewed publications and conference contributions. TRIAL REGISTRATION NUMBER: NCT04478201.

Psychometric Properties and Predictive Value of a Screening Questionnaire for Obstructive Sleep Apnea in Young Children With Down Syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS) and is associated with adverse health and cognitive outcomes. Daytime clinical assessment is poorly predictive of OSA, so regular screening with sleep studies is recommended. However, sleep studies are costly and not available to all children worldwide. We aimed to evaluate the psychometric properties and predictive value of a newly developed screening questionnaire for OSA in this population. METHODS: 202 children aged 6 months to 6th birthday with DS were recruited, of whom 188 completed cardio-respiratory sleep studies to generate an obstructive apnea hypopnea index (OAHI). Parents completed the 14-item Down syndrome OSA screening questionnaire. Responses were screened, a factor analysis undertaken, internal consistency calculated and receiver operator characteristic (ROC) curves drawn to generate an area under the curve (AUC) to assess criterion related validity. RESULTS: Of 188 children who completed cardiorespiratory sleep studies; parents completed the screening questionnaire for 186. Of this study population 15.4% had moderate to severe OSA defined by an OAHI of ≥5/h. Sixty-three (33.9%) participants were excluded due to "unsure" responses or where questions were not answered. Using the remaining 123 questionnaires a four-factor solution was found, with the 1st factor representing breathing related symptoms, explaining a high proportion of the variance. Internal consistency was acceptable with a Cronbach alpha of 0.87. ROC curves for the total score generated an AUC statistic of 0.497 and for the breathing subscale an AUC of 0.603 for moderate to severe OSA. CONCLUSION: A well designed questionnaire with good psychometric properties had limited predictive value to screen for moderate to severe OSA in young children with DS. The use of a screening questionnaire is not recommended. Screening for OSA in this population requires objective sleep study measures.

Sleep in infants and toddlers with Down syndrome compared to typically developing peers: looking beyond snoring.

AIMS: To compare sleep in infants and toddlers with Down syndrome (DS) to typically developing controls, including differences in snoring and sleep ecology (sleep setting and parent behaviors). METHODS: Parents of 104 children with DS and 489 controls aged 6-36 months completed the Brief Infant Sleep Questionnaire (BISQ). We explored group differences, controlling for demographic variables. RESULTS: Parents of children with DS reported more sleep problems (45% v 19%), snoring (19% vs 2%), room-sharing (37% vs 17%), as well as less night-time sleep (55 mins) and total sleep over 24 h (38 mins). They were more likely to be present when their child fell asleep (OR 4.40). Snoring increased night waking but did not limit night-time/24-hour sleep. However, parental presence was associated with 55 min less night-time and 64 min less 24-hour sleep. After controlling for snoring and parental presence, children with DS slept less at night (38 mins) but more during the day (21 mins) with no significant difference in 24-hour sleep. CONCLUSIONS: Overall, significant differences in sleep patterns, problems, and ecology were found between children with DS and controls. Parental presence at settling, not snoring, explained most differences, including over an hour's less 24-hour sleep. Early intervention programmes that promote self-soothing skills could prevent the burden of sleep loss in young children with DS.

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.

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.