Perth Childrens Hospital Foundation

Background Urinary tract infections (UTIs) are the most common serious bacterial infections in febrile infants. Current UK guidelines recommend parenteral antibiotics for infants under three months with suspected UTI, despite evidence supporting oral therapy in low-risk infants. Objectives To assess whether oral antibiotics are non-inferior to parenteral antibiotics for treating suspected UTIs based on treatment failure, need for additional therapy, and secondary outcomes. Design Multicentre, randomised controlled, open-label, non-inferiority trial with embedded internal pilot. Setting Twenty one paediatric emergency departments and assessment units across the UK. Participants Infants aged 29–90 days with suspected UTI, abnormal urinalysis, and low risk of invasive bacterial infection. Exclusion criteria included prematurity, prior hospitalisation, structural renal abnormalities, and clinical signs of sepsis or meningitis. Interventions Participants were randomised 1:1 to receive either oral antibiotics or standard care with intravenous (IV) antibiotics for 36–48 hours pending urine culture results. Main outcome measures The primary outcome was the requirement for additional parenteral antibiotics within seven days of randomisation. A range of secondary outcomes were also planned, including treatment failure, time to recovery, adverse events, antibiotic adherence, quality of life, family impact, and healthcare resource use. Feasibility outcomes collected during the internal pilot included recruitment rate, site activation, protocol adherence, and retention. Clinical outcomes were collected but not powered for formal comparison. Results 27 participants were recruited between 20 May 2024 and 13 March 2025 (which included the 6 month internal pilot), representing 27% of the pilot target. Protocol adherence was high, and no cases of meningitis occurred. Two cases of bacteraemia (one per randomised group) had uncomplicated clinical courses. Oral therapy was associated with shorter hospital stays and reduced parental time off work. Conclusions While trial procedures were successfully implemented, recruitment challenges suggest that a larger randomised trial of this treatment comparison is not feasible in this setting. Trial management Northern Ireland Clinical Trials Unit (NICTU) Trial registration ISRCTN Clinical Trials Registry, ISRCTN10907780, Trial Dates 20 May 2024 to 13 March 2025

Silver-Russell syndrome (SRS OMIM 180860) is a rare, albeit well-recognized disorder characterized by severe intrauterine and postnatal growth retardation. It remains a clinical diagnosis with a molecular cause identifiable in approximately 60%-70% of patients. We report a 4-year-old Australian Aboriginal girl who was born at 32 weeks gestation with features strongly suggestive of SRS, after extensive investigation she was referred to our undiagnosed disease program (UDP). Genomic sequencing was performed which identified a heterozygous splice site variant in IGF2 which is predicted to be pathogenic by in-silico studies, paternal allelic origin, de novo status, and RNA studies on fibroblasts. We compare clinical findings with reported patients to add to the knowledge base on IGF2 variants and to promote the engagement of other Australian Aboriginal families in genomic medicine.