Early childhood parent-reported speech problems in small and large for gestational age term-born and preterm-born infants: a cohort study

Objective (1) To assess if preterm and term small for gestational age (SGA) or large for gestational age (LGA) infants have more parent-reported speech problems in early childhood compared with infants with birth weights appropriate for gestational age (AGA). (2) To assess if preterm and term SGA and LGA infants have more parent-reported learning, behavioural, hearing, movement and hand problems in early childhood compared with AGA infants. Design Cohort study. Setting Wales, UK. Participants 7004 children with neurodevelopmental outcomes from the Respiratory and Neurological Outcomes of Children Born Preterm Study which enrolled 7129 children, born from 23 weeks of gestation onwards, to mothers aged 18–50 years of age were included in the analysis. Outcome measures Parent-reported single-answer questionnaires were completed in 2013 to assess early childhood neurodevelopmental outcomes. The primary outcome was parent-reported speech problems in early childhood adjusted for clinical and demographic confounders in SGA and LGA infants compared with AGA infants. Secondary outcomes measured were parent-reported early childhood learning, behavioural, hearing, movement and hand problems. Results Median age at the time of study was 5 years, range 2–10 years. Although the adjusted OR was 1.19 (0.92 to 1.55) for SGA infants and OR 1.11 (0.88 to 1.41) for LGA infants, this failed to reach statistical significance that these subgroups were more likely to have parent-reported speech problems in early childhood compared with AGA infants. This study also found parent-reported evidence suggestive of potential learning difficulties in early childhood (OR 1.51 (1.13 to 2.02)) and behavioural problems (OR 1.35 (1.01 to 1.79)) in SGA infants. Conclusion This study of 7004 infants in Wales suggests that infants born SGA or LGA likely do not have higher risks of parent-reported speech problems in early childhood compared with infants born AGA. To further ascertain this finding, studies with wider population coverage and longer-term follow-up would be needed

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Respiratory distress of the term newborn infant

Respiratory distress is recognised as any signs of breathing difficulties in neonates. In the early neonatal period respiratory distress is common, occurring in up to 7% of newborn infants, resulting in significant numbers of term-born infants being admitted to neonatal units. Many risk factors are involved; the increasing number of term infants delivered by elective caesarean section has also increased the incidence. Additionally the risk decreases with each advancing week of gestation. At 37 weeks, the chances are three times greater than at 39-40 weeks gestation. Multiple conditions can present with features of respiratory distress. Common causes in term newborn infants include transient tachypnoea of the newborn, respiratory distress syndrome, pneumonia, meconium aspiration syndrome, persistent pulmonary hypertension of the neonate and pneumothorax. Early recognition of respiratory distress and initiation of appropriate treatment is important to ensure optimal outcomes. This review will discuss these common causes of respiratory distress in term-born infants

The effect of birth weight on lung spirometry in white, school-aged children and adolescents born at term: a longitudinal population based observational cohort study

Objective To evaluate how birth weight affects lung function measurements in childhood and adolescence in term-born children. Study design We used data for white, term-born, singletons, from the Avon Longitudinal Study of Parents and Children to determine the association between birth weight and lung function at age 8-9 (n = 4086) and 14-17 (n = 2582) years. z-scores for lung function measures, adjusted for sex, height, and age, were modeled in terms of birth weight z-score adjusted for sex. In addition, gestation and head circumference then confounders (maternal smoking during pregnancy and social class) were added to the model. Results At age 8-9 years, birth weight z-scores were significantly associated with lung function z-scores (forced expiratory volume in 1 second, forced vital capacity [FVC], and forced mid-expiratory flow between 25% and 75% of FVC). These relationships essentially were unchanged when birth weight z-scores were further adjusted for gestation, head circumference, and confounders, except for forced mid-expiratory flow between 25% and 75% of FVC, which was no longer significant after we adjusted for head circumference and confounders. At age 14-17 years, the associations between adjusted birth-weight z-scores and spirometry z-scores were in general not significant. Estimated differences for forced expiratory volume in 1 second were 30 mL at ages 8-9 years and 33 mL at 14-17 years for 1 kg change in birth-weight standardized for gestation and sex. Conclusions Birth weight is associated with lung function in term-born children at 8-9 years, but less so at 14-17 years, suggesting that birth weight influences lung function in early childhood but has lesser effect later in life

An analysis of the effect of intrauterine growth retardation on spirometric lung function measures of 8-year-old children [Abstract]

Objective Increasing evidence suggests that intrauterine growth retardation (IUGR) is associated with long-term morbidities, including respiratory outcomes. The relationship between IUGR and lung function has been studied in adults, but few studies have investigated childhood respiratory outcomes and it is unclear if catch-up growth in these children influences lung function. We investigated the hypothesis that lung function differs in 8- to 9-year-old children born at term between those that were within normal weight bands and those that had growth retardation. Additionally, in the growth-retarded group, we investigated if lung function differed between those who did and those who did not show weight catch up. Design The Avon Longitudinal Study of Parents and Children birth cohort. Participants The 5770 Caucasian singleton births of 37 weeks or longer gestation who had lung function assessed at 8–9 years. We classified 576 infants as IUGR as their gestation-appropriate birthweight fell below the 10th centile. This group was compared with those 3462 non-IUGR infants whose birthweights fell between the 20th and 80th centiles. Main outcome measure and results The non-IUGR infants had significantly better lung function at 8–9 years of age than those with IUGR. The differences between the standardised (z) lung function values, adjusted for sex, gestation, maternal smoking during pregnancy, and social class, and 95% CI were FEV1: −0.198 (−0.294 to −0.102); FVC: −0.131 (−0.227 to −0.036); FEF 25–75: −0.149 (−0.246 to −0.053). The groups had similar respiratory symptoms. Catch-up growth for weight was defined as an increase in z score of at least 0.67 between birth and ages 8–9 years. For the IUGR children, 430 caught up and 146 did not. All spirometry measurements were higher in IUGR children who experienced catch-up growth than in those without, although the differences were not statistically significant. Both groups remained significantly lower than control subjects. Growth-retarded asymmetric and symmetric children had similar lung function. Conclusion We concluded that IUGR is associated with poorer lung function at 8–9 years of age compared with control children. Although the differences were not statistically significant, spirometry was higher in children who showed weight catch-up growth, but remained significantly lower than in the control children

Effect of late preterm birth on longitudinal lung spirometry in school age children and adolescents

Background: Rates of preterm birth have increased in most industrialised countries but data on later lung function of late preterm births are limited. A study was undertaken to compare lung function at 8–9 and 14–17 years in children born late preterm (33–34 and 35–36 weeks gestation) with children of similar age born at term (≥37 weeks gestation). Children born at 25–32 weeks gestation were also compared with children born at term. Methods: All births from the Avon Longitudinal Study of Parents and Children (n=14 049) who had lung spirometry at 8–9 years of age (n=6705) and/or 14–17 years of age (n=4508) were divided into four gestation groups. Results: At 8–9 years of age, all spirometry measures were lower in the 33–34-week gestation group than in controls born at term but were similar to the spirometry decrements observed in the 25–32-week gestation group. The 35–36-week gestation group and term group had similar values. In the late preterm group, at 14–17 years of age forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were not significantly different from the term group but FEV1/FVC and forced expiratory flow at 25–75% FVC (FEF25–75%) remained significantly lower than term controls. Children requiring mechanical ventilation in infancy at 25–32 and 33–34 weeks gestation had in general lower airway function (FEV1 and FEF25–75) at both ages than those not ventilated in infancy. Conclusions: Children born at 33–34 weeks gestation have significantly lower lung function values at 8–9 years of age, similar to decrements observed in the 25–32-week group, although some improvements were noted by 14–17 years of age

Effect of preterm birth on later FEV1: a systematic review and meta-analysis

Background Increasing evidence suggests that preterm birth affects later lung function. We systematically reviewed the literature to determine whether percentage predicted forced expiratory volume in 1 s (%FEV1) is lower in later life in preterm-born subjects, with or without bronchopulmonary dysplasia (BPD), compared with term-born controls. Methods Studies reporting %FEV1, with or without a term-born control group, in later life for preterm-born subjects (<37 weeks gestation) were extracted from eight databases. Data were analysed using Review Manager and STATA. The quality of the studies was assessed. Results From 8839 titles, 1124 full articles were screened and 59 were included: 28 studied preterm-born children without BPD, 24 with BPD28 (supplemental oxygen dependency at 28 days), 15 with BPD36 (supplemental oxygen dependency 36 weeks postmenstrual age) and 34 born preterm. For the preterm-born group without BPD and for the BPD28 and BPD36 groups the mean differences (and 95% CIs) for %FEV1 compared with term-born controls were −7.2% (−8.7% to −5.6%), −16.2% (−19.9% to −12.4%) and −18.9% (−21.1% to −16.7%), respectively. Pooling all data on preterm-born subjects whether or not there was a control group gave a pooled %FEV1 estimate of 91.0% (88.8% to 93.1%) for the preterm-born cohort without BPD, 83.7% (80.2% to 87.2%) for BPD28 and 79.1% (76.9% to 81.3%) for BPD36. Interestingly, %FEV1 for BPD28 has improved over the years. Conclusions %FEV1 is decreased in preterm-born survivors, even those who do not develop BPD. %FEV1 of survivors of BPD28 has improved over recent years. Long-term respiratory follow-up of preterm-born survivors is required as they may be at risk of developing chronic obstructive pulmonary disease

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