Impact of ambient air pollution on lung function in preterm-born school-aged children.

RATIONALE: Increased outdoor air pollution worsens lung function in children. However, these associations are less well studied in preterm-born individuals. OBJECTIVES: We assessed associations between ambient air pollutants and spirometry measures in preterm-born children. METHODS: The Respiratory Health Outcomes in Neonates study recruited preterm-born children aged 7-12 years who were born at ≤34 week's gestation. We associated four ambient air pollutants (particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), PM10, nitrogen dioxide (NO2) and sulfur dioxide) at time of birth and spirometry assessment and averaged exposure between these two time points with spirometry measures, using linear regression analyses. Gestational age was banded into 23-28, 29-31 and 32-34 week's. Regression models estimated spirometry values against pollutant levels at birth and at the time of spirometry. MEASUREMENTS AND MAIN RESULTS: From 565 preterm-born children, 542 (96%) had satisfactory data. After adjustments for early and current life factors, significant detrimental associations were noted between PM10 at birth and per cent predicted forced vital capacity (%FVC) for the 23-28 and 29-31 week's gestation groups and between current PM2.5 and NO2 exposure and %FVC for the 23-28 week's gestation group. No associations with spirometry were noted for the averaged pollution exposure between birth and spirometry. Predictive models showed 5.9% and 7.4% differences in %FVC between the highest and lowest current pollution exposures for PM2.5 and NO2, respectively, in the 23-28 week group. CONCLUSIONS: Birth and current exposures to road-traffic-associated pollutants detrimentally affected %FVC in preterm-born school-aged children, who already have compromised lung function.

Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study.

INTRODUCTION: Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system's biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age. METHODS AND ANALYSIS: We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 µL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent. ETHICS AND DISSEMINATION: The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. TRIAL REGISTRATION NUMBER: NCT04904523.

Characterisation of Staphylococci species from neonatal blood cultures in low- and middle-income countries.

BACKGROUND: In low- and middle-income countries (LMIC) Staphylococcus aureus is regarded as one of the leading bacterial causes of neonatal sepsis, however there is limited knowledge on the species diversity and antimicrobial resistance caused by Gram-positive bacteria (GPB). METHODS: We characterised GPB isolates from neonatal blood cultures from LMICs in Africa (Ethiopia, Nigeria, Rwanda, and South Africa) and South-Asia (Bangladesh and Pakistan) between 2015-2017. We determined minimum inhibitory concentrations and performed whole genome sequencing (WGS) on Staphylococci isolates recovered and clinical data collected related to the onset of sepsis and the outcome of the neonate up to 60 days of age. RESULTS: From the isolates recovered from blood cultures, Staphylococci species were most frequently identified. Out of 100 S. aureus isolates sequenced, 18 different sequence types (ST) were found which unveiled two small epidemiological clusters caused by methicillin resistant S. aureus (MRSA) in Pakistan (ST8) and South Africa (ST5), both with high mortality (n = 6/17). One-third of S. aureus was MRSA, with methicillin resistance also detected in Staphylococcus epidermidis, Staphylococcus haemolyticus and Mammaliicoccus sciuri. Through additional WGS analysis we report a cluster of M. sciuri in Pakistan identified between July-November 2017. CONCLUSIONS: In total we identified 14 different GPB bacterial species, however Staphylococci was dominant. These findings highlight the need of a prospective genomic epidemiology study to comprehensively assess the true burden of GPB neonatal sepsis focusing specifically on mechanisms of resistance and virulence across species and in relation to neonatal outcome.

The incidence of avascular necrosis following a cohort of treated developmental dysplasia of the hip in a single tertiary centre.

PURPOSE: Avascular necrosis (AVN) may occur following treatment for developmental dysplasia of the hip (DDH). The primary aim of this study was to identify the incidence of AVN in a cohort of patients treated for DDH. Secondary aims were to classify AVN using available classification systems, analyze the correlation between the systems and investigate their relationship with the age at diagnosis of DDH. METHODS: An 11-year retrospective study was carried out at a single tertiary centre, using data from the clinical portal (patient records database) and IMPAX (system used to store plain radiographic images). Clinical details (patient demographics and outcomes) and plain radiographic images were used to identify cases of DDH and categorize cases of AVN using available classification systems: Tonnis and Kuhlmann, Kalamchi and McEwen, Bucholz and Ogden and Salter. Severin was used to assess final clinical outcome. RESULTS: In total, 405 (522 hips) cases of DDH were identified, of which 213 resolved without treatment, 93 were treated conservatively and 99 surgically. Only treated cases were included in the analysis (n = 192). AVN (45/99; 45.5%) was found to occur only postoperatively. A positive correlation was present between age at presentation and severity of AVN as classified according to Salter's criteria (chi-squared p value < 0.01). CONCLUSION: AVN incidence was 23.4% (45/192) and only occurred in surgically treated patients. Older age at diagnosis was associated with a higher incidence of AVN, as defined according to Salter's criteria. The classification systems appeared to show no correlation amongst each other (p-value < 0.01). LEVEL OF EVIDENCE: III - Retrospective cohort study.

Determinants of Stillbirth From Two Observational Studies Investigating Deliveries in Kano, Nigeria.

BACKGROUND: Stillbirths are a poignant representation of global inequality. Nigeria is documented to have the second highest rate; yet, the reporting system is inadequate in most Nigerian healthcare facilities. The aim was to identify the determinants of stillbirth among deliveries in the Murtala Muhammad Specialist Hospital (MMSH), Kano, Nigeria. METHODS: Two study designs were used: a case-control study (S1) and a prospective cohort study (S2). Both studies were carried out at the MMSH. For S1, stillbirths were retrospectively matched to a livebirth by time (target of 24 hours' time variation) to establish a case-control study with a 1:1 ratio. Eligibility into S2 included all mothers who were presented at the MMSH in labour regardless of birth outcome. Both were based on recruitment durations, not sample sizes (3 months and 2 months, respectively, 2017-2018). The demographic and clinical data were collected through paper-based questionnaires. Univariable logistic regression was used. Multivariable logistic regression was used to explore relationships between area type and other specific factors. FINDINGS: Stillbirth incidence in S2 was 180/1,000 births. Stillbirth was associated with the following factors; no maternal education, previous stillbirth(s), prematurity, living in both semi-rural and rural settings, and having extended time periods between rupture of membranes and delivery. Findings of the multivariable analysis (S1 and S2) indicated that the odds of stillbirth, for those living in a rural area, were further exacerbated in those mothers who had no education, lived in a shack, or had any maternal disease. INTERPRETATION: This research identifies the gravity of this situation in this area and highlights the need for action. Further understanding of some of the findings and exploration into associations are required to inform intervention development. FUNDING: This collaboration was partially supported by funding from Health and Care Research Wales.

Predicting extubation outcomes using the Heart Rate Characteristics index in preterm infants: a cohort study.

A strategy of early extubation to noninvasive respiratory support in preterm infants could be boosted by the availability of a decision support tool for clinicians. Using the Heart Rate Characteristics index (HRCi) with clinical parameters, we derived and validated predictive models for extubation readiness and success.Peri-extubation demographic, clinical and HRCi data for up to 96 h were collected from mechanically ventilated infants in the control arm of a randomised trial involving eight neonatal centres, where clinicians were blinded to the HRCi scores. The data were used to produce a multivariable regression model for the probability of subsequent re-intubation. Additionally, a survival model was produced to estimate the probability of re-intubation in the period after extubation.Of the 577 eligible infants, data from 397 infants (69%) were used to derive the pre-extubation model and 180 infants (31%) for validation. The model was also fitted and validated using all combinations of training (five centres) and test (three centres) centres. The estimated probability for the validation episodes showed discrimination with high statistical significance, with an area under the curve of 0.72 (95% CI 0.71-0.74; p<0.001). Data from all infants were used to derive models of the predictive instantaneous hazard of re-intubation adjusted for clinical parameters.Predictive models of extubation readiness and success in real-time can be derived using physiological and clinical variables. The models from our analyses can be accessed using an online tool available at www.heroscore.com/extubation, and have the potential to inform and supplement the confidence of the clinician considering extubation in preterm infants.

Predicting Extubation Outcomes-A Model Incorporating Heart Rate Characteristics Index.

OBJECTIVE: To test the hypothesis that in neonates on mechanical ventilation, heart rate characteristics index (HRCi) can be combined with a clinical model for predicting extubation outcomes in neonates. STUDY DESIGN: HRCi and clinical data for all intended intubation-extubation events (episodes) were retrospectively analyzed between June 2014 and January 2015. Each episode started 6 hours pre-extubation or at the time of primary intubation if ventilation duration was shorter than 6 hours (baseline). The episodes ended at 72 hours postextubation for successful extubations or at reintubation for failed extubations. Mean of 6 hourly epoch HRCi-scores (baseline) or fold-changes (postextubation) were analyzed. Results are expressed as medians (IQR) for continuous data and proportions for categorical data. Multivariable logistic regression mixed model was used for statistical analysis. RESULTS: Sixty-six infants contributed to 96 episodes (18 failed extubations, 78 successful extubations) in the study. Failed extubations had significantly longer duration of ventilation (65.3 hours, 19.94-158.2 vs 38.4, 16.5-71.3) and more culture positive sepsis (33.3% vs 3.8%) than successful extubations. Baseline HRCi scores (1.68, 1.29-2.45 vs 0.95, 0.54-1.86) and postextubation epoch-1 fold changes (1.25, 0.94-1.55 vs 0.94, 0.82-1.11) were higher in failed extubations compared with successful extubations. Multivariable linear mixed-effects regression was used to create prediction models for success of extubation, using relevant variables. CONCLUSIONS: The baseline and postextubation HRCi were significantly higher in neonates with extubation failure compared with those who succeeded. Models using HRCi and clinical variables to predict extubation success may add to the confidence of clinicians considering extubation.

Effect of early-term birth on respiratory symptoms and lung function in childhood and adolescence.

BACKGROUND: Early-term-born subjects, (37-38 weeks' gestation), form a large part of the population and have an increased risk of neonatal respiratory morbidity and childhood respiratory symptoms; there is a paucity of data on their later lung function. We sought to (1) compare lung function at 8-9 and 14-17 years in early-term-born children with full-term-born children (39-43 weeks' gestation); (2) assess the role of caesarean section delivery; and (3) compare respiratory symptoms and diagnosis of asthma. METHODS: Caucasian, singleton, term births from the Avon Longitudinal Study of Parents and Children (n = 14,062) who had lung spirometry at 8-9 (n = 5,465) and/or 14-17 (n = 3,666) years were classified as early or full term. RESULTS: At 8-9 years, standardized spirometry measures, although within the normal range, were lower in the early-term-born group, (n = 911), compared to full-term controls (n = 4,554). Delivery by caesarean section did not influence later spirometry, and the effect of early-term birth was not modified by delivery by caesarean section. At 14-17 years, the spirometry measures in the early-term group, (n = 602), were similar to the full-term group (3,064), and the rates of asthma and respiratory symptoms were also similar between the two gestation groups. CONCLUSIONS: Early-term-born children had lower lung function values at 8-9 years compared to the full-term group, but were similar by 14-17 years of age. Delivery at early term should be avoided due to early and late morbidity. Pediatr Pulmonol. 2016;51:1212-1221. © 2016 Wiley Periodicals, Inc.

Higher systolic blood pressure with normal vascular function measurements in preterm-born children.

UNLABELLED: Preterm birth, low birth weight and poor foetal nutrition have been linked to cardiovascular disease, but the underlying mechanisms remain unclear. We explored prematurity and vascular function by studying a UK cohort of 14 049 children and conducting a systematic review. CONCLUSION: Systolic blood pressure was higher in subjects born preterm than term, but there were no differences in endothelial dysfunction or arterial stiffness. The systematic review revealed no clear association between prematurity and vascular function.

Tidal breathing in preterm infants receiving and weaning from continuous positive airway pressure.

OBJECTIVE: To compare tidal breathing on different continuous positive airway pressure (CPAP) devices and pressures and to serially measure tidal breathing during weaning off CPAP using electromagnetic inductive plethysmography. STUDY DESIGN: Using electromagnetic inductive plethysmography, tidal breathing was measured in 29 preterm infants receiving CPAP, gestational age 28 ± 2 weeks. Variable-flow nasal CPAP (nCPAP), bubble CPAP (bCPAP) at pressures of 5, 7, and 9 cmH2O, nasal bi-level positive airway pressure (nBiPAP) system at pressures of 5, 7/5, and 9/5 cmH2O, and unsupported breathing were studied. Twenty-one infants had weekly tidal breathing measurements on and off nCPAP. RESULTS: Minute volume (MV/kg) was similar between all devices (0.30-0.33 L/kg/min). On bCPAP, weight corrected tidal volume (VT/kg) was the least, changing little with increasing pressures. On nCPAP and nBiPAP, VT/kg increased with increasing pressure and the respiratory rate (fR) decreased. The delivered pressure varied slightly from the set pressure being most dissimilar on nBiPAP and similar on bCPAP. Compared with unsupported breathing, all devices decreased VT/kg, MV/kg, and phase angle, but did not alter fR. Serial tidal breathing measurements showed decreasing difference for VT/kg over time on and off nCPAP. CONCLUSIONS: At different pressure settings, on all CPAP devices the measured MV/kg was similar either through increasing VT/kg and decreasing fR (nCPAP and nBiPAP) or maintaining both (bCPAP). Serial tidal breathing measurements may aid weaning from CPAP.

Defining background DNA levels found on the skin of children aged 0-5 years.

There are currently no data available regarding the normal levels of DNA found on the skin of children engaging in routine day to day activities to assist with the forensic interpretation of DNA profiles generated from skin surface swabs. To address this deficit, skin surface swab samples were collected from 12 face/neck sites and 20 body sites on 50 children less than 5 years old. After exclusion of spoilt samples, 60 sets of swabs from 47 children (30 face/neck, 30 body) comprising of 944 individual samples were analysed. The number of alleles observed which could have originated from the child and the number which must have come from another source (non-child) were analysed. The following variables were evaluated: age, kissing, feeding and washing practices, number of contacts and application of cream. Overall, extremely small amounts of non-child DNA were retrieved from skin swabs. Child only (46.3%) or no DNA at all (18.6%) was observed for 64.9% of all swabbed samples. Low levels of non-child DNA (1-5 alleles) were observed on 31.6% of all swabs tested with only 3.4% of swabs showing six or more alleles. A great deal of variation between children and between sites in the levels of both child DNA and non-child DNA was observed. A multilevel model, taking account of clustering within children, showed that there was a strong direct association between the amounts of child and non-child DNA observed. There was no relationship between the amount of DNA recovered and the demographic and biographic variables analysed. These background data have the potential to assist the analysis of DNA from the skin of children during criminal investigation.