Objective: To identify risk factors associated with mortality in critically ill children requiring continuous renal replacement therapy. Design: Retrospective observational study based on a prospective registry. Setting: Tertiary and quaternary referral 30-bed PICU. Patients: Critically ill children undergoing continuous renal replacement therapy were included in the study. Interventions: Continuous renal replacement therapy. Measurements and Main Results: Overall mortality was 36% (n = 58) among the 161 patients treated with continuous renal replacement therapy during the study period and was significantly higher in patients on extracorporeal membrane oxygenation (47.5%, 28 of 59) than in patients not requiring extracorporeal membrane oxygenation (28.4%, 29 of 102; p = 0.022). According to the admission diagnosis, we found the highest mortality in patients with onco-hematologic disease (77.8%) and the lowest in patients with renal disease (5.6%). Based on multivariate logistic regression analysis, the presence of higher severity of illness score at admission (adjusted odds ratio, 1.49; 95% CI, 1.18–1.89; p < 0.001), onco-hematologic disease (odds ratio, 17.10; 95% CI, 4.10–72.17; p < 0.001), fluid overload 10%–20% (odds ratio, 3.83; 95% CI, 1.33–11.07; p = 0.013), greater than 20% (odds ratio, 15.03; 95% CI, 4.03–56.05; p < 0.001), and timing of initiation of continuous renal replacement therapy (odds ratio, 1.01; 95% CI, 1.00–1.01; p = 0.040) were independently associated with mortality. In our population, the odds of dying increases by 1% for every hour of delay in continuous renal replacement therapy initiation from ICU admission. Conclusions: Mortality in children requiring continuous renal replacement therapy remains high and seems to be related to the underlying disease, the severity of illness, and the degree of fluid overload. In critically ill children at high risk for developing acute kidney injury and fluid overload, earlier initiation of continuous renal replacement therapy might result in decreased mortality.

Objectives: The role of venoarterial extracorporeal membrane oxygenation in the treatment of severe pediatric septic shock continues to be intensely debated. Our objective was to determine whether the use of venoarterial extracorporeal membrane oxygenation in severe septic shock was associated with altered patient mortality, morbidity, and/or length of ICU and hospital stay when compared with conventional therapy. Design: International multicenter, retrospective cohort study using prospectively collected data of children admitted to intensive care with a diagnosis of severe septic shock between the years 2006 and 2014. Setting: Tertiary PICUs in Australia, New Zealand, Netherlands, United Kingdom, and United States. Patients: Children greater than 30 days old and less than 18 years old. Interventions: None. Measurements and Main Results: Of 2,452 children with a diagnosis of sepsis or septic shock, 164 patients met the inclusion criteria for severe septic shock. With conventional therapy (n = 120), survival to hospital discharge was 40%. With venoarterial extracorporeal membrane oxygenation (n = 44), survival was 50% (p = 0.25; CI, –0.3 to 0.1). In children who suffered an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy and 42% with venoarterial extracorporeal membrane oxygenation (Δ = 24%; p = 0.02; CI, 2.5–42%). Survival was significantly higher in patients who received high extracorporeal membrane oxygenation flows of greater than 150 mL/kg/min compared with children who received standard extracorporeal membrane oxygenation flows or no extracorporeal membrane oxygenation (82%, 43%, and 48%; p = 0.03; CI, 0.1–0.7 and p < 0.01; CI, 0.2–0.7, respectively). Lengths of ICU and hospital stay were significantly longer for children who had venoarterial extracorporeal membrane oxygenation. Conclusions: The use of venoarterial extracorporeal membrane oxygenation in severe pediatric sepsis is not by itself associated with improved survival. However, venoarterial extracorporeal membrane oxygenation significantly reduces mortality after cardiac arrest due to septic shock. Venoarterial extracorporeal membrane oxygenation flows greater than 150 mL/kg/min are associated with almost twice the survival rate of conventional therapy or standard-flow extracorporeal membrane oxygenation.

BACKGROUND: Age-specific reference intervals (RIs) have been developed for biochemistry analytes in children. However, the ability to interpret results from multiple laboratories for 1 individual is limited. This study reports a head-to-head comparison of reference values and age-specific RIs for 30 biochemistry analytes for children across 5 analyzer types.METHODS: Blood was collected from healthy newborns and children 30 days to <18 years of age. Serum aliquots from the same individual were analyzed on 5 analyzer types. Differences in the mean reference values of the analytes by the analyzer types were investigated using mixed-effect regression analysis and by comparing maximum variation between analyzers with analyte-specific allowable total error reported in the Westgard QC database. Quantile regression was used to estimate age-specific RIs using power variables in age selected by fractional polynomial regression for the mean, with modification by sex when appropriate.RESULTS: The variations of age-specific mean reference values between analyzer types were within allowable total error (Westgard QC) for most analytes, and common age-specific reference limits were reported as functions of age and/or sex. Analyzer-specific reference limits for all analytes on 5 analyzer types are also reported as functions of age and/or sex.CONCLUSIONS: This study provides quantitative and qualitative measures of the extent to which results for individual children can or cannot be compared across analyzer types, and the feasibility of RI harmonization. The reported equations enable incorporation of age-specific RIs into laboratory information systems for improving evidence-based clinical decisions in children.

Background: Globally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety. Methods and findings: Between 4 July 2018 and 18 May 2021, infants born at ≥32⁺⁰ weeks’ gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm. Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference −6 bpm, 95% confidence interval (CI) −17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal–infant bonding and higher iron stores. Conclusions: In this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32⁺⁰ weeks’ gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.

Introduction Being transgender is frequently accompanied by gender dysphoria, which often coexists with mental health concerns. Increased referrals of transgender and gender diverse (TGD) youth to gender clinics have been observed in many countries. Nevertheless, there are limited empirical data on the presentation and outcomes of these patients, and there is an urgent need for more evidence to ensure optimal medical and psychosocial interventions. Here, we describe Trans20, a longitudinal study of TGD patients attending a multidisciplinary paediatric gender service in Melbourne, Australia. Trans20 aims to understand the demographic and clinical characteristics of these patients, to document the natural history of gender diversity presenting in childhood and to investigate long-term outcomes for those receiving interventions. Methods and analysis Trans20 is a prospective cohort study based on children and adolescents first seen at the Royal Children’s Hospital Gender Service (RCHGS) between February 2017 and February 2020. Current estimates indicate the final sample size will be approximately 600. Patients and their parents complete online questionnaires prior to the first appointment with RCHGS and regularly thereafter as part of routine clinical care. On discharge from RCHGS, patients are invited to continue undertaking questionnaires biennially. In this way, a naturally forming cohort study has been created. The primary outcomes include gender dysphoria, physical and mental health, schooling, family functioning and quality of life. Subgroup analyses based on factors such as gender identity, birth-assigned sex and treatment received will be performed using bivariate and multivariate modelling as appropriate, and relevant statistical methods will be applied for the repeated measures over time. Ethics and dissemination The Royal Children's Hospital Human Research Ethics Committee approved this study (#36323). Findings from Trans20 will have translational impact by informing future treatment guidelines and gender affirming healthcare practices and will be disseminated through conferences and peer reviewed journals.