Supplementary Material for: Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Neonates With Early-Onset Infection

Background: The discriminative utility of the neonatal sequential organ failure assessment (nSOFA) for early-onset sepsis (EOS) mortality in the neonatal intensive care unit (NICU) is unknown. Objectives: Determine the utility of nSOFA for EOS mortality. Methods: Multicenter, retrospective cohort study of NICU patients with EOS between 2012-2023. nSOFA scores of survivors and non-survivors were compared and area under receiver operating characteristics curve (AUROC) for mortality was calculated. Results: 104 subjects were identified (88 lived, 16 died). AUROC at blood culture collection (T0), 6 hours after collection(T6), and the maximum nSOFA at T0 or T6 (T0-6max) were 0.76 (95% CI 0.62, 0.91), 0.89 (0.80, 0.99), and 0.87 (0.77, 0.97), respectively. Analyses restricted to birthweight (<1.5, <1kg) or gestational age (<32, <29 week) cutoffs revealed AUROC ranges of 0.86-0.92 for T6 and 0.82-0.84 for T0-6max. Conclusions: The nSOFA showed good-to-excellent discrimination of mortality among infants with EOS in the NICU

Supplementary Material for: Colorimetric CO2 Detector to Improve Effective Mask Ventilations in Very Preterm Infants: A Pilot Randomized Controlled Study

Introduction: End tidal CO2 (ETCO2) detector is currently recommended for confirmation of endotracheal tube placement during neonatal resuscitation. Whether it is feasible to use ETCO2 detectors during mask ventilation to reduce risk of bradycardia and desaturations, which are associated with increased risk of death in preterm babies, is unknown. Methods : This is a pilot randomized controlled trial ((NCT04287907) involving newborns 24+0/7 to 32+0/7 weeks gestation who required mask ventilation at birth. Infants were randomized into groups with or without colorimetric ETCO2 detectors. Combined duration of any bradycardia (<100bpm) and time below prespecified target oxygen saturations (SpO2) as measured by pulse oximetry were compared. Results : Fifty participants were randomized, 47 with outcomes analysed (2 incomplete data, 1 postnatal diagnosis of trachea-esophageal fistula). Mean gestational age and birthweight were 28.5±1.9 vs 29.4±1.6 weeks, (p=0.1) and 1252.7±409.7g vs 1334.6±369.1g, (p=0.5) in the intervention and control arm respectively. Mean combined duration of bradycardia and desaturation was 276.7±197.7s (intervention) and 322.7±277.7s (control),(p=0.6). Proportion of participants with any bradycardia or desaturation at 5 minutes were 38.1% (intervention) and 56.5% (control), (p=0.2). No chest compressions, epinephrine administration or death occurred in the delivery room. Conclusion: This pilot study demonstrates that the feasibility of a trial to evaluate colorimetric ETCO2 detectors during mask ventilation of very preterm infants to reduce bradycardia and low SpO2. Further assessment with a larger population will be required to determine if ETCO2 detectors usage at resuscitation reduces risk of adverse outcomes, including death and disability, in very preterm infants

Supplementary Material for: International online survey on the management of patent ductus arteriosus

Introduction There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. Materials and Methods We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. Results There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment and 42% reported variable management within their own unit. Among infants <28 weeks (or <1000g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs 18% all countries [OR 4.1; 95% CI 2.6-6.5; p<0.001]) and respondents from North America were more likely to treat symptomatic PDA (67% vs 60% all countries [OR 2.0; 95% CI 1.5-2.6; p<0.001]). In infants ≥28 weeks (or ≥1000g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs 38% all countries [OR 2.3; 95% CI 1.7-3.2]; p<0.001) and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs 7% all countries [OR 5.5; 95% CI 3.2-9.8; p<0.001]). Discussion/Conclusion There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated

Supplementary Material for: “Mild’’ Hypoxic-Ischaemic Encephalopathy and Therapeutic Hypothermia: A Survey of Clinical Practice and Opinion from 35 Countries

Introduction: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE). Methods: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries. Results: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p v HIC 26%, p v HIC 32%, p v HIC 40%, p v HIC 95%, p Conclusions: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider “cooling” an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported