OBJECTIVES:To evaluate the methodological quality of hospital-specific paediatric sepsis clinical practice guidelines (CPGs) from sites participating in an international study using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and to assess the consistency of treatment recommendations and concordance with the Surviving Sepsis Campaign 2020 (SSC 2020) international reference standard. DESIGN:Cross-sectional appraisal of hospital-specific CPGs. SETTING:Hospital sites participating in the Sepsis Epidemiology in Paediatric Acute Care International Study across five continents. PARTICIPANTS:Hospital-specific CPGs for the acute care management of paediatric sepsis. INTERVENTIONS:Hospital-specific CPGs were appraised independently using the AGREE II tool and classified as high, moderate or low quality. Consistency across guidelines and concordance with SSC 2020 were assessed for 12 key treatment recommendations. MAIN OUTCOME MEASURES:AGREE II domain scores and overall quality rating; consistency of treatment recommendations across hospital-specific CPGs; concordance of individual CPGs with SSC 2020. RESULTS:14 hospital-specific CPGs from 13 countries were included. All were rated as low methodological quality overall; the rigour of development (range: 0-50%) and editorial independence (0-58%) were the lowest scoring AGREE II domains. CPG concordance with SSC 2020 ranged from 42% to 100%; consistency across the 12 treatment recommendations ranged from 43% (steroid indications) to 93% (initial laboratory investigations, time to antibiotics and fluid bolus volume). CONCLUSIONS:Despite all hospital-specific CPGs across an international cohort being of low methodological quality, most aligned with SSC 2020 for key time-critical recommendations. Clinically important variations existed in fluid resuscitation composition and timing of steroid administration. TRIAL REGISTRATION NUMBER:ACTRN12621000920097.
Aim To understand the extent and implications of night-to-night variability (NTNV) in obstructive sleep apnoea (OSA) screening for children with Down syndrome (DS). Design Retrospective review of outpatient OSA screening data, assessing NTNV across three consecutive nights of pulse oximetry (3NPO) studies and comparing results of screening oximetry and diagnostic polygraphy (PG). Two hundred and forty-six 3NPO studies in patients aged 1 to <18 years with DS at University Hospital Southampton NHS Foundation Trust between April 2020 and December 2024 were included. Clinically significant NTNV was defined as results above and below the published screening thresholds predictive of moderate-to-severe OSA in children with DS (3% oxygen desaturation index (ODI3) ≥6.15 and delta index (D12s) ≥0.555) on nights within the same 3NPO study. Receiver operating characteristic curve analysis was used to identify optimal lower reassurance threshold values to account for NTNV. Results Fifty-three per cent of the 150 complete 3NPO studies showed clinically significant NTNV. Children with night 1 results below the reassurance thresholds ODI3 3.61 (n=19) and D12s 0.49 (n=64) had a low chance of abnormal result on subsequent nights (negative predictive value 79% and 81%, respectively). Eighty-seven per cent of night 1 oximetry data fell above these thresholds. Sixty per cent of PG studies showed OSA. Seventy-six per cent of moderate-to-severe OSA was in children aged >6 years. Conclusions Clinically significant NTNV was seen in the majority of 3NPO studies. Single-night screening may miss children who would screen positive on multiple-night testing. UK screening recommendations may need revision to reflect NTNV and significant OSA prevalence in older children.
OBJECTIVES:To describe haemolytic disease outcomes, growth, neurodevelopment and health-related quality of life (HRQoL) through 24 months of life in infants exposed to nipocalimab in pregnancies at high risk of early-onset severe haemolytic disease of the fetus and newborn (EOS-HDFN). DESIGN:A multicentre, open-label, single-arm trial. SETTING:Centres with expertise in HDFN management. PATIENTS:Pregnant individuals with previous EOS-HDFN and maternal anti-D titres ≥32 or anti-K titres ≥4. INTERVENTIONS:Weekly nipocalimab (30 and/or 45 mg/kg) from 14 to 35 gestational weeks. MAIN OUTCOME MEASURES:Infants' cord-blood alloantibody titres at birth, HDFN management, growth through 6 months, neurodevelopment (caregiver-reported Ages and Stages Questionnaire, third edition (ASQ-3)) and HRQoL assessments through 24 months of life. RESULTS:Of 13 pregnancies, 12 resulted in live births; one fetal loss occurred due to intrauterine transfusion (IUT) complications. A single simple transfusion was administered in one of seven infants delivered after a maternal nipocalimab course without IUTs, where cord blood alloantibody titres were <8. Multiple transfusions (one to seven simple transfusions/infant; one exchange transfusion) were administered to five infants delivered after early nipocalimab discontinuation and IUTs, with cord-blood alloantibody titres ranging from 512 to 32 768. No unusual growth patterns were observed through 6 months. No neurodevelopmental delays were identified through 24 months of life, with mean ASQ-3 domain scores within normal ranges. HRQoL outcomes were positive across physical, emotional, social and cognitive functioning. CONCLUSIONS:Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life. TRIAL REGISTRATION NUMBER:NCT03842189.
OBJECTIVE:Skeletal surveys play an important role in detecting occult injury in young children at risk from non-accidental injury. Current UK safeguarding guidance (2018) advises two skeletal surveys within 2 weeks in children under 2 years old. The first is a full survey (plus a CT head scan if under 1 year), alongside a secondary survey using selected views of the chest and long bones. Recent work suggested the rarity of detected injury did not justify the second exposure to ionised radiation. We wished to explore this important issue further. DESIGN:Retrospective audit of all skeletal surveys in infants aged under 2 years against these guidelines between 1 January 2018 and 18 February 2025. SETTING:Children's Hospital for Wales. PATIENTS:Local children having radiological examinations for safeguarding evaluation. Out-of-area children were excluded. INTERVENTIONS:Two skeletal surveys. MAIN OUTCOME MEASURES:Adherence to guidelines in performing two surveys within 2 weeks, plus fracture rates found in first and second surveys. RESULTS:Investigations performed in 186 children; 16 had only the primary survey and 2 were over 2 years leaving 168 for evaluation (90.3%). Secondary surveys carried out within 14 days in 161/168 (95.8%). Patients were classified in five presentation groups: bruise or skin lesion (n=106), fractures (n=43), domestic violence (n=15), fracture in sibling (n=2) and head injury (n=2). Skeletal surveys classified as normal, indeterminate or abnormal. 10/168 (6.0%) had fractures additional to the presenting injury on primary skeletal survey, 12/168 (7.1%) had additional fractures on secondary skeletal survey and 1/168 (0.6%) had a normal primary survey but fracture found solely on secondary survey. CONCLUSIONS:A clinically important number of additional injuries and occasional new ones are found on second skeletal surveys. Our work supports the ongoing use of the current radiological investigation protocol with two surveys for this vulnerable group.
OBJECTIVE:To evaluate neurodevelopmental outcomes at 2-3 years of age among survivors of extremely preterm infant (EPI). DESIGN AND SETTING:Analysis of prospectively collected Australian and New Zealand Neonatal Network data on infants born <28 weeks' gestation between 2010 and 2019. MAIN OUTCOME:The prevalence of neurodevelopmental impairment (NDI), defined as any moderate to severe cerebral palsy (CP), sensory impairment or developmental delay (score <70) at 2-3 years of age was determined. Epoch comparisons (2010-204 vs 2015-2019) and the impact of major morbidity on NDI were examined, adjusting for maternal age, antenatal steroids, gestational age, Apgar score, admission temperature, sex and breast milk feeding. RESULTS:Of 6617 EPIs, 15.5% had NDI. Developmental delay was most prevalent (14.5%), including language (11.1%), motor (5.9%), cognitive (5.7%) domains, followed by CP (3.2%), deafness (1.4%) and blindness (0.4%). Compared with infants without morbidity, adjusted odds of NDI increased with one (adjusted OR (aOR) 1.50, 95% CI 1.21 to 1.84), two (aOR 2.09, 95% CI 1.60 to 2.53) and three or more coexisting morbidities (aOR 3.56, 95% CI 2.73 to 4.65). Between epochs, bronchopulmonary dysplasia increased by 6.9% and retinopathy of prematurity by 3.8%, alongside a rise in developmental delay (10.3% to 17.8%), contributing to a 6.6% absolute increase in NDI. Survivors born at 22-23 weeks had the highest NDI rates, increasing from 23.0% to 26.4%. CONCLUSION:NDI rates among EPI increased over time and were associated with increasing multiple morbidities. Although changes in EPIs survival patterns may have contributed to these trends, reducing neonatal morbidities and strengthening neuroprotective care remain priorities.
OBJECTIVE:Breast milk is the optimal source of nutrition for preterm infants; however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers' yeast or beta-glucan improves daily expressed breast milk volume. DESIGN:Randomised, blinded, parallel, placebo-controlled trial. SETTING:Three Australian tertiary-level neonatal units. PATIENTS:Mothers with a singleton or twin pregnancy who gave birth at <34 weeks' gestation. INTERVENTIONS:Mothers were randomised within 72 hours of birth into three parallel groups in a 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for 7 days. MAIN OUTCOME MEASURE:Total expressed breast milk volume over a 24-hour period on day 7 of intervention. RESULTS:A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94 mL/day (95% CI -51 mL/day to 239 mL/day) between the brewers' yeast and placebo groups and -25 mL/day (95% CI -173 mL/day to 123 mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. CONCLUSION:We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. TRIAL REGISTRATION NUMBER:ACTRN12622000968774.
Functional neurological disorder is a common reason for children to present to the emergency department, but education gaps contribute to delays in diagnosis. This can result in unnecessary diagnostic testing and interventions, which lead to increased healthcare costs and, at times, patient harm. In this narrative review, we provide practical recommendations regarding emergency department management of paediatric functional neurological disorder. We recommend that emergency physicians use the described rule-in signs rather than negative medical tests to make a positive diagnosis of functional neurological disorder. We advocate for timely communication of this diagnosis to the patient and family in a clear and validating way. We also discuss considerations for patient triage, outpatient referrals and special scenarios that emergency physicians may frequently encounter.
OBJECTIVE:To explore the feasibility of a randomised controlled trial (RCT) of donor human milk (DHM) use for preterm infants with mother's own milk (MOM) shortfall, assessing DHM impact on breastfeeding. DESIGN:Feasibility, open-label RCT. SETTING:Two tertiary neonatal intensive care units in the UK. PATIENTS:135 infants born before 33 weeks' gestation or with birth weight <1500 g whose mothers intended to provide MOM admitted between June 2021 and March 2023. INTERVENTIONS:Infants were randomly assigned to either DHM for MOM shortfall until full feeds (FFs) and preterm formula thereafter, control (DHM-FF group) or the intervention, DHM until 36 weeks corrected gestational age (CGA) or discharge if sooner (DHM-36w group). MAIN OUTCOME MEASURES:Feasibility outcomes included study recruitment, retention and intervention feasibility measures. The primary clinical outcome was breastfeeding or receipt of any MOM at 36 weeks CGA or discharge if sooner. Secondary clinical outcomes included growth and neonatal morbidities. RESULTS:Of 325 screened infants, 247 were eligible, out of which 135 were recruited (54.7%). Parents of 36 infants declined DHM. Three infants discontinued DHM use during the study. 13 infants could not access the intervention due to transfer.38/66 (57.6%) infants from the DHM-FF group and 40/69 (58%) infants from the DHM-36w group received some MOM at 36 weeks' CGA. There were no significant differences between groups in growth and morbidity outcomes. CONCLUSIONS:The RCT design is feasible for future, larger-scale studies. Availability of MOM did not differ between groups at 36 weeks but was higher than historical cohorts. TRIAL REGISTRATION NUMBER:57339063.
INTRODUCTION:There is confusion in practice regarding the role of adolescents in consenting to their participation in medical research. There are lack of studies investigating the views of adolescents on the process of consenting to participate in research and what this should look like. This study provides a qualitative account of adolescents' views on this process. METHODS:Qualitative interviews or written responses were collected from 25 adolescents (aged 14-17 years). Views were explored using a story completion method, where participants were given a stem scenario and asked to state what they thought should happen next. Thematic analysis was undertaken to identify key codes and themes. RESULTS:Our participants saw parents as an important source of information and often valued their advice. They wanted to make autonomous, informed decisions and thought their parents would contribute to the process of becoming informed. They assessed the risk of participation based on trust of familiar institutions and processes. DISCUSSION:English law sees adolescent medical consent in terms of competence but is not clear about research consent. We may be doing a disservice to adolescents by not providing support to help adolescents attain competence prior to decision-making. This could be provided by a parent or another trusted adult. CONCLUSION:Our participants valued input from their parents and want to be supported in making decisions regarding participation in medical research.
Objective This study aims to describe the differences in Paediatric Critical Care Transport (PCCT) timings across the UK and Ireland to help explore challenges in access faced by different regional teams. Design Retrospective cohort study. Setting Emergency transports to paediatric intensive care units (PICUs) across the UK and Ireland where data were captured by the Paediatric Intensive Care Audit Network. Population Children under 16 years of age requiring emergency PICU transport between 1 January 2018 and 31 December 2022. Main outcome measures Incidence of PICU transport and the variations in the time taken for the transport teams to mobilise and reach the bedside. Results Over the 5-year period, there were 20 167 transports of 17 834 children. Over 40% (n=8561) of transports were undertaken by two PCCTs based in London and Southeast England. The greatest risk of mortality (Paediatric Index of Mortality (PIM3)>5%) was seen across children transported by PCCTs covering England and Wales (median PIM3>5%=26.0%). Only PCCT services in England achieved a median time to mobilise <30 min. Nearly 25% of transports by the three teams covering Scotland, Southwest England, South Wales and Ireland took >3 hours to reach the bedside. Conclusions This is the first cohort study comparing timing differences between PCCT services and highlighting the different challenges. Delays in PCCT mobilisation may suggest operational or resource difficulties.
Directed acyclic graphs (DAGs) are increasingly recommended or required by journals for observational studies making causal claims yet few paediatric observational studies present DAGs to support their analytical approach. This practical guide addresses the implementation gap between methodological guidance and research practice by clarifying when DAGs are needed (causal questions only, not descriptive or predictive research), demonstrating how to construct them for paediatric studies, and explaining how to use them to identify appropriate statistical adjustment strategies. We illustrate common pitfalls, including adjusting for colliders and mediators, address practical challenges such as temporal ordering ambiguity, and provide a worked example from recent paediatric literature. Proper use of DAGs makes causal assumptions explicit, prevents common analytical errors and strengthens causal inference in observational paediatric research.
OBJECTIVE:To examine ethnic differences in the incidence and timing of recorded health conditions from birth to adolescence between White British and Pakistani British children. DESIGN:Longitudinal population-based birth cohort linked to primary care electronic health records. SETTING:Born in Bradford (BiB), a multiethnic UK birth cohort. PARTICIPANTS:13 282 children born between 2007 and 2011 with linked primary care records and ≥1-year follow-up, including 4818 White British and 5878 Pakistani British children in the primary comparison. MAIN OUTCOME MEASURES:Recorded diagnoses of atopic conditions, overweight/obesity, common mental health disorders and neurodevelopmental disorders. Incidence rates, Kaplan-Meier cumulative incidence and sex-adjusted Cox regression HRs were estimated. RESULTS:Atopic conditions emerged early and were more common among Pakistani British children, with higher hazards of eczema (HR 2.29, 95% CI 2.01 to 2.61), allergic rhinoconjunctivitis (HR 2.27, 2.00 to 2.58) and asthma (HR 1.35, 1.22 to 1.50). Overweight/obesity was recorded later and was also more frequent in Pakistani British children (HR 1.25, 1.16 to 1.35). In contrast, common mental health and neurodevelopmental diagnoses were more frequently recorded among White British children; Pakistani British children had lower hazards of neurodevelopmental diagnoses (HR 0.28, 0.23 to 0.35) and mental health disorders (HR 0.53, 0.41 to 0.70). CONCLUSIONS:Ethnic differences in recorded health conditions between White British and Pakistani British children were condition-specific and varied by age. These findings identify when recorded diagnoses diverge in Bradford and highlight the need to distinguish differences in morbidity from differences in recognition, access, assessment, and recording.
