Genetic Analyses in Small for Gestational Age Newborns

Context: Small for gestational age (SGA) can be a result of fetal growth restriction, associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood. Objective: The aim of the present study was to gain more insight into prenatal growth failure and determine an effective diagnostic approach in SGA newborns. We hypothesized that one or more CNVs and disturbed methylation and sequence variants may be present in genes known to be associated with fetal growth. Design: A prospective cohort study of subjects with a low birthweight for gestational age. Setting: The study was conducted at an academic pediatric research institute. Patients: A total of 21 SGA newborns with a mean birthweight below the 1st centile and a control cohort of 24 appropriate for gestational age newborns were studied. Intervention: Array comparative genomic hybridization, genome-wide methylation studies and exome sequencing were performed. Main Outcome Measures The numbers of copy number variations, methylation disturbances and sequence variants. Results: The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern and one sequence variant explaining the SGA. Additional methylation disturbances and sequence variants were present 20 patients. In 19 patients, multiple abnormalities were found. Conclusion: Our results confirm the influence of a large number of mechanisms explaining dysregulation of fetal growth. We conclude that copy number variations, methylation disturbances and sequence variants all contribute to prenatal growth failure. Such genetic workup can be an effective diagnostic approach in SGA newborns

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries