Intervention at an early threshold for post-hemorrhagic ventricular dilatation in preterm infants: a systematic review and meta-analysis.

BACKGROUND: Very few adequately powered studies exploring early thresholds for intervention in the management of post-hemorrhagic ventricular dilatation (PHVD) in preterm infants have identified consistent neurodevelopmental advantages at 12-30 months. We aimed to conduct a meta-analysis on the efficacy and safety of early versus conservative thresholds for intervention, primarily aimed at normalizing cerebrospinal fluid (CSF) pressure, in the management of PHVD in preterm infants. METHODS: Multiple databases were searched for eligible papers, and prospective randomized trials involving preterm infants were selected. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). The main outcome was survival without moderate-to-severe neurodevelopmental impairment at 12-30 months. RESULTS: Ten articles representing seven randomized trials comparing early versus conservative thresholds for interventions were included. Five trials (n = 545 infants) reported no difference in the main outcome between early and conservative groups [RR 0.99 (0.71, 1.37)]. Sensitivity analysis excluding data from a medication trial did not alter the main outcome [RR 1.15 (0.95, 1.39)]. Infants in the early threshold group received significantly more interventions [RR 1.48 (1.05, 2.09)]. Deaths before discharge/during the initial study period [RR 1.04 (0.70, 1.54)] or a composite of death or shunt insertion [RR 1.04 (0.86, 1.27)] were comparable between the two groups. CONCLUSIONS: Early intervention for PHVD, before a clinical or ultrasound threshold is met, leads to additional clinical procedures but does not improve survival without moderate-severe neurodevelopmental impairment at 12-30 months. Caution should be exercised in interpreting these results due to significant variation between the studies. Supplementary file 3 (MP4 131172 kb).

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.