ABSTRACT
BACKGROUND: Differentiating infants with adverse events following immunisation (AEFIs) or invasive bacterial infection (IBI) is a significant clinical challenge. Young infants post vaccination are therefore often admitted to the hospital for parenteral antibiotics to avoid missing rare cases of IBI. METHODS: During a service evaluation project, we conducted a single-centre retrospective observational study of infants with IBI, urinary tract infection (UTI) or AEFI from two previously published cohorts. All patients presented to hospital in Oxfordshire, UK, between 2011 and 2018, spanning the introduction of the capsular group-B meningococcal vaccine (4CMenB) into routine immunisation schedules. Data collection from paper and electronic notes were unblinded. Clinical features, including National Institute for Health and Care Excellence (NICE) 'traffic light' risk of severe illness and laboratory tests performed on presentation, were described, and comparisons made using regression models, adjusting for age and sex. We also compared biochemical results on presentation to those of well infants post vaccination, with and without 4CMenB regimens. RESULTS: The study included 232 infants: 40 with IBI, 97 with probable AEFI, 24 with possible AEFI, 27 with UTI and 44 post vaccination 'well' infants. C-reactive protein (CRP) was the only discriminatory blood marker, with CRP values above 83 mg/L only observed in infants with IBI or UTI. NICE risk stratification was significantly different between groups but still missed cases of IBI, and classification as intermediate risk was non-differential. Fever was more common in probable AEFI cases, while seizures and rashes were equally frequent. Diarrhoea and clinician-reported irritability or rigours were all more common in IBI. CONCLUSIONS: Clinical features on presentation may aid risk stratification but cannot reliably differentiate IBI from AEFI in infants presenting to the emergency department. Blood results are generally unhelpful due to post vaccination inflammatory responses, particularly in children receiving 4CMenB vaccination. Improved biomarkers and clinical prediction tools are required to aid management in febrile infants post vaccination.
Subject(s)
Bacterial Infections , Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup B , Urinary Tract Infections , Humans , Infant , Bacterial Infections/diagnosis , Bacterial Infections/epidemiology , C-Reactive Protein , Emergency Service, Hospital , Fever/etiology , Fever/chemically induced , Meningococcal Infections/chemically induced , Meningococcal Infections/prevention & control , Meningococcal Vaccines/adverse effects , Retrospective Studies , Urinary Tract Infections/diagnosis , Urinary Tract Infections/epidemiology , Urinary Tract Infections/chemically inducedSubject(s)
Schools, Medical , Students, Medical , Curriculum , Female , Humans , Pregnancy , Stillbirth , Surveys and QuestionnairesSubject(s)
Bereavement , Curriculum/standards , Education, Medical , Parents/psychology , Stillbirth/psychology , Education, Medical/methods , Education, Medical/standards , Emotional Intelligence/ethics , Humans , Needs Assessment , Professional-Family Relations/ethics , Social Skills , Social Support , Surveys and Questionnaires , United KingdomABSTRACT
Genome-wide association studies in the fields of reproductive medicine and endocrinology are yielding robust genetic variants associated with disease. Integrated genomic, transcriptomic, and epigenomic molecular profiling studies are common methodologies used to understand the biologic pathways perturbed by these variants. However, molecular profiling resources do not include the tissue most relevant to many female reproductive traits, the endometrium, while the parameters influencing variability of results from its molecular profiling are unclear. We investigated the sources of DNA methylation and RNA expression profile variability in endometrium (n = 135), endometriotic disease tissue (endometriosis), and subcutaneous abdominal fat samples from 24 women, quantifying between-individual, within-tissue (cellular heterogeneity), and technical variation. DNA samples (n = 96) were analyzed using Illumina HumanMethlylation450 BeadChip arrays; RNA samples (n = 39) were analyzed using H12-expression arrays. Variance-component analyses showed that, for the top 10-50% variable DNA methylation/RNA expression sites, between-individual variation far exceeded within-tissue and technical variation. Menstrual-phase accounted for most variability in methylation/expression patterns in endometrium (Pm = 7.8 × 10-3, Pe = 8.4 × 10-5) but not in fat and endometriotic tissue; age was significantly associated with DNA methylation profile of endometrium (Pm = 9 × 10-5) and endometriotic disease tissue (Pm = 2.4 × 10-5); and smoking was significantly associated with DNA methylation in adipose tissue (Pm = 1.8 × 10-3). Hierarchical cluster analysis showed significantly different methylation signatures between endometrium and endometriotic tissue enriched for WNT signaling, angiogenesis, cadherin signaling, and gonadotropin-releasing-hormone-receptor pathways. Differential DNA methylation/expression analyses suggested detection of a limited number of sites with large fold changes (FC > 4), but power calculations accounting for different sources of variability showed that for robust detection >500 tissue samples are required. These results enable appropriate study design for large-scale expression and methylation tissue-based profiling relevant to many reproductive and endocrine traits.
