Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Oxygen for the delivery room respiratory support of moderate-to-late preterm infants. An international survey of clinical practice from 21 countries.

AIM: The aim of this study was to determine clinician opinion regarding oxygen management in moderate-late preterm resuscitation. METHODS: An anonymous online questionnaire was distributed through email/social messaging platforms to neonatologists in 21 countries (October 2020-March 2021) via REDCap. RESULTS: Of the 695 respondents, 69% had access to oxygen blenders and 90% had pulse oximeters. Respondents from high-income countries were more likely to have oxygen blenders than those from middle-income countries (72% vs. 66%). Most initiated respiratory support with FiO2 0.21 (43%) or 0.3 (36%) but only 45% titrated FiO2 to target SpO2 . Most (89%) considered heart rate as a more important indicator of response than SpO2 . Almost all (96%) supported the need for well-designed trials to examine oxygenation in moderate-late preterm resuscitation. CONCLUSION: Most clinicians resuscitated moderate-late preterm infants with lower initial FiO2 but some cannot/will not target SpO2 or titrate FiO2 . Most consider heart rate as a more important indicator of infant response than SpO2 .Large and robust clinical trials examining oxygen use for moderate-late preterm resuscitation, including long-term neurodevelopmental outcomes, are supported amongst clinicians.

Progesterone in women with arrested premature labor, a report of a randomised clinical trial and updated meta-analysis.

BACKGROUND: Progesterone may be effective in prevention of premature birth in some high risk populations. Women with arrested premature labor are at risk of recurrent labor and maintenance therapy with standard tocolytics has not been successful. METHODS: Randomized double blinded clinical trial of daily treatment with 200 mg vaginal progesterone in women with arrested premature labor and an updated meta-analysis. RESULTS: The clinical trial was terminated early after 41 women were enrolled. Vaginal progesterone treatment did not change the median gestational age at delivery: 36+2 weeks versus 36+4 weeks, p = .865 nor increase the mean latency to delivery: 44.5 days versus 46.6 days, p = .841. In the updated meta-analysis, progesterone treatment did reduce delivery <37 weeks gestation and increase latency to delivery, but this treatment effect was not evident in the high quality trials: (OR 1.23, 95% CI 0.91, 1.67) and (-0.95 days, 95% CI -5.54, 3.64) respectively. CONCLUSION: Progesterone is not effective for preventing preterm birth following arrested preterm labor.

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

Objective Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this.

Chorioamnionitis at birth does not increase the risk of neurodevelopmental disability in premature infants with bronchopulmonary dysplasia.

AIM: To compare preterm infants with no bronchopulmonary dysplasia (BPD), BPD with chorioamnionitis (BPDC) and BPD with no chorioamnionitis (BPDNC) for the association with neurodevelopmental disability (NDD) at three years corrected age. METHODS: Demographic and outcome data of infants with birthweight (BW) ≤1250 g born during two epochs (1995-2000 and 2002-2007 with an interim washout period of one year) were compared on the basis of whether they had BPD, chorioamnionitis or both. Any NDD was considered present if there was either mild-severe cerebral palsy (CP), cognitive delay, visual or hearing impairment. Logistic regression modelling was performed. RESULTS: Infants (n = 1009) were included into three groups - no BPD (n = 442), BPDNC (n = 437) and BPDC (n = 130). The adjusted odds ratio (aOR) of any NDD at three years in infants with BPDC versus BPDNC was 1.37; 95% CI 0.85-2.20, and for CP the aOR was 1.66; 95% CI 0.76-3.62. Infants in the BPDC group were of lower BW, gestational age and had longer length of hospital stay, duration of mechanical ventilation, more blood transfusions and sepsis compared to BPDNC and no BPD groups (all p < 0.001). CONCLUSION: Chorioamnionitis was not associated with any increase in the odds of NDD in infants with BPD at three years corrected age.

Clinicians in 25 countries prefer to use lower levels of oxygen to resuscitate preterm infants at birth.

AIM: This study determined current international clinical practice and opinions regarding initial fractional inspired oxygen (FiO2 ) and pulse oximetry (SpO2 ) targets for delivery room resuscitation of preterm infants of less than 29 weeks of gestation. METHODS: An online survey was disseminated to neonatal clinicians via established professional clinical networks using a web-based survey programme between March 9 and June 30, 2015. RESULTS: Of the 630 responses from 25 countries, 60% were from neonatologists. The majority (77%) would target SpO2 between the 10th to 50th percentiles values for full-term infants. The median starting FiO2 was 0.3, with Japan using the highest (0.4) and the UK using the lowest (0.21). New Zealand targeted the highest SpO2 percentiles (median 50%). Most respondents agreed or did not disagree that a trial was required that compared the higher FiO2 of 0.6 (83%), targeting the 50th SpO2 percentile (60%), and the lower FiO2 of 0.21 (80%), targeting the 10th SpO2 percentile (78%). Most (65%) would join this trial. Many considered that evidence was lacking and further research was needed. CONCLUSION: Clinicians currently favour lower SpO2 targets for preterm resuscitation, despite acknowledging the lack of evidence for benefit or harm, and 65% would join a clinical trial.

Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants.

IMPORTANCE: Extremely preterm infants may experience intermittent hypoxemia or bradycardia for many weeks after birth. The prognosis of these events is uncertain. OBJECTIVE: To determine the association between intermittent hypoxemia or bradycardia and late death or disability. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks. Follow-up assessments occurred between October 2008 and August 2012. EXPOSURES: Episodes of hypoxemia (pulse oximeter oxygen saturation <80%) or bradycardia (pulse rate <80/min) for 10 seconds or longer. Values were sampled every 10 seconds within 24 hours after birth until at least 36 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death after 36 weeks' postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months' corrected age. Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity. RESULTS: Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0 days). Mean percentages of recorded time with hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively. Corresponding values for bradycardia were 0.1% and 0.3%. The primary outcome was ascertained for 972 infants and present in 414 (42.6%). Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94). This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05 vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32). Relative risks for all secondary outcomes were similarly increased after prolonged hypoxemia. Bradycardia did not alter the prognostic value of hypoxemia. CONCLUSIONS AND RELEVANCE: Among extremely preterm infants who survived to 36 weeks' postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes. If confirmed in future studies, further research on the prevention of such episodes is needed.

Impact of study oximeter masking algorithm on titration of oxygen therapy in the Canadian oxygen trial.

OBJECTIVE: To compare oxygen saturations as displayed to caregivers on offset pulse oximeters in the 2 groups of the Canadian Oxygen Trial. STUDY DESIGN: In 5 double-blind randomized trials of oxygen saturation targeting, displayed saturations between 88% and 92% were offset by 3% above or below the true values but returned to true values below 84% and above 96%. During the transition, displayed values remained static at 96% in the lower and at 84% in the higher target group during a 3% change in true saturations. In contrast, displayed values changed rapidly from 88% to 84% in the lower and from 92% to 96% in the higher target group during a 1% change in true saturations. We plotted the distributions of median displayed saturations on days with >12 hours of supplemental oxygen in 1075 Canadian Oxygen Trial participants to reconstruct what caregivers observed at the bedside. RESULTS: The oximeter masking algorithm was associated with an increase in both stability and instability of displayed saturations that occurred during the transition between offset and true displayed values at opposite ends of the 2 target ranges. Caregivers maintained saturations at lower displayed values in the higher than in the lower target group. This differential management reduced the separation between the median true saturations in the 2 groups by approximately 3.5%. CONCLUSIONS: The design of the oximeter masking algorithm may have contributed to the smaller-than-expected separation between true saturations in the 2 study groups of recent saturation targeting trials in extremely preterm infants.

Impact of oxygen concentration on time to resolution of spontaneous pneumothorax in term infants: a population based cohort study.

BACKGROUND: Little evidence exists regarding the optimal concentration of oxygen to use in the treatment of term neonates with spontaneous pneumothorax (SP). The practice of using high oxygen concentrations to promote "nitrogen washout" still exists at many centers. The aim of this study was to identify the time to clinical resolution of SP in term neonates treated with high oxygen concentrations (HO: FiO2 ≥ 60%), moderate oxygen concentrations (MO: FiO2 < 60%) or room air (RA: FiO2 = 21%). METHODS: A population based cohort study that included all term neonates with radiologically confirmed spontaneous pneumothorax admitted to all neonatal intensive care units in Calgary, Alberta, Canada, within 72 hours of birth between 2006 and 2010. Newborns with congenital and chromosomal anomalies, meconium aspiration, respiratory distress syndrome, and transient tachypnea of newborn, pneumonia, tension pneumothorax requiring thoracocentesis or chest tube drainage or mechanical ventilation before the diagnosis of pneumothorax were excluded. The primary outcome was time to clinical resolution (hours) of SP. A Cox proportional hazards model was developed to assess differences in time to resolution of SP between treatment groups. RESULTS: Neonates were classified into three groups based on the treatment received: HO (n = 27), MO (n = 35) and RA (n = 30). There was no significant difference in time to resolution of SP between the three groups, median (range 25th-75th percentile) for HO = 12 hr (8-27), MO = 12 hr (5-24) and RA = 11 hr (4-24) (p = 0.50). A significant difference in time to resolution of SP was also not observed after adjusting for inhaled oxygen concentration [MO (a HR = 1.13, 95% CI 0.54-2.37); RA (a HR = 1.19, 95% CI 0.69-2.05)], gender (a HR = 0.87, 95% CI 0.53-1.43) and ACoRN respiratory score (a HR = 0.7, 95% CI 0.41-1.34). CONCLUSIONS: Supplemental oxygen use or nitrogen washout was not associated with faster resolution of SP. Infants treated with room air remained stable and did not require supplemental oxygen at any point of their admission.

Fast and accurate newborn heart rate monitoring at birth: A systematic review.

Aim: To examine speed and accuracy of newborn heart rate measurement by various assessment methods employed at birth. Methods: A search of Medline, SCOPUS, CINAHL and Cochrane was conducted between January 1, 1946, to until August 16, 2023. (CRD 42021283364) Study selection was based on predetermined criteria. Reviewers independently extracted data, appraised risk of bias and assessed certainty of evidence. Results: Pulse oximetry is slower and less precise than ECG for heart rate assessment. Both auscultation and palpation are imprecise for heart rate assessment. Other devices such as digital stethoscope, Doppler ultrasound, an ECG device using dry electrodes incorporated in a belt, photoplethysmography and electromyography are studied in small numbers of newborns and data are not available for extremely preterm or bradycardic newborns receiving resuscitation. Digital stethoscope is fast and accurate. Doppler ultrasound and dry electrode ECG in a belt are fast, accurate and precise when compared to conventional ECG with gel adhesive electrodes. Limitations: Certainty of evidence was low or very low for most comparisons. Conclusion: If resources permit, ECG should be used for fast and accurate heart rate assessment at birth. Pulse oximetry and auscultation may be reasonable alternatives but have limitations. Digital stethoscope, doppler ultrasound and dry electrode ECG show promise but need further study.

Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis.

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial.

IMPORTANCE: The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in preterm infants. OBJECTIVE: To compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel in which 1201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012. INTERVENTIONS: Study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced 2 treatment groups with true target saturations of 85% to 89% (n = 602) or 91% to 95% (n = 599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury. RESULTS: Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI, 0.85 to 1.37; P = .52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI, 0.80 to 1.54; P = .54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, -0.8 weeks; 95% CI, -1.5 to -0.1; P = .03) but did not alter any other outcomes. CONCLUSION AND RELEVANCE: In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months. These results may help determine the optimal target oxygen saturation. TRIAL REGISTRATIONS: ISRCTN Identifier: 62491227; ClinicalTrials.gov Identifier: NCT00637169.

Exhaled CO2 monitoring to guide non-invasive ventilation at birth: a systematic review.

OBJECTIVE: Measuring exhaled carbon dioxide (ECO2) during non-invasive ventilation at birth may provide information about lung aeration. However, the International Liaison Committee on Resuscitation (ILCOR) only recommends ECO2 detection for confirming endotracheal tube placement. ILCOR has therefore prioritised a research question that needs to be urgently evaluated: 'In newborn infants receiving intermittent positive pressure ventilation by any non-invasive interface at birth, does the use of an ECO2 monitor in addition to clinical assessment, pulse oximetry and/or ECG, compared with clinical assessment, pulse oximetry and/or ECG only, decrease endotracheal intubation in the delivery room, improve response to resuscitation, improve survival or reduce morbidity?'. DESIGN: Systematic review of randomised and non-randomised studies identified by Ovid MEDLINE, Embase and Cochrane CENTRAL search until 1 August 2022. SETTING: Delivery room. PATIENTS: Newborn infants receiving non-invasive ventilation at birth. INTERVENTION: ECO2 measurement plus routine assessment compared with routine assessment alone. MAIN OUTCOME MEASURES: Endotracheal intubation in the delivery room, response to resuscitation, survival and morbidity. RESULTS: Among 2370 articles, 23 were included; however, none had a relevant control group. Although studies indicated that the absence of ECO2 may signify airway obstruction and ECO2 detection may precede a heart rate increase in adequately ventilated infants, they did not directly address the research question. CONCLUSIONS: Evidence to support the use of an ECO2 monitor to guide non-invasive positive pressure ventilation at birth is lacking. More research on the effectiveness of ECO2 measurement in addition to routine assessment during non-invasive ventilation of newborn infants at birth is needed. PROSPERO REGISTRATION NUMBER: CRD42022344849.

Respiratory function monitoring during neonatal resuscitation: A systematic review.

Aim: Positive pressure ventilation via a facemask is critical in neonatal resuscitation, but frequently results in mask leak, obstruction, and inadequate respiratory support. This systematic review aimed to determine whether the display of respiratory function monitoring improved resuscitation or clinical outcomes. Methods: Randomized controlled trials comparing outcomes when respiratory function monitoring was displayed versus not displayed for newborns requiring positive pressure ventilation at birth were selected and from databases (last search August 2022), and assessed for risk of bias using Cochrane Risk of Bias Tools for randomized control trials. The study was registered in the Prospective Register of Systematic Reviews. Grading of Recommendations, Assessment, Development and Evaluations was used to assess the certainty of evidence. Treatment recommendations were approved by the Neonatal Life Support Task Force of the International Liaison Committee on Resuscitation. Results reported primary and secondary outcomes and included resuscitation and clinical outcomes. Results: Of 2294 unique articles assessed for eligibility, three randomized controlled trials were included (observational studies excluded) (n = 443 patients). For predefined resuscitation and clinical outcomes, these studies either did not report the primary outcome (time to heart rate ≥ 100 bpm from birth), had differing reporting methods (achieving desired tidal volumes, significant mask leak) or did not find significant differences (intubation rate, air leaks, death before hospital discharge, severe intraventricular hemorrhage, chronic lung disease). Limitations included limited sample size for critical outcomes, inconsistent definitions amongst studies and unreported long-term outcomes. Conclusion: Although respiratory function monitoring has been utilized in clinical care, there is currently insufficient evidence to suggest its benefit for newborn infants receiving respiratory support for resuscitation at birth. Registration: PROSPERO CRD42021278169 (registered November 27, 2021). Funding: The International Liaison Committee on Resuscitation provided support that included access to software platforms and teleconferencing.

Supraglottic Airways Compared With Face Masks for Neonatal Resuscitation: A Systematic Review.

BACKGROUND AND OBJECTIVES: Positive pressure ventilation (PPV) is the most important component of neonatal resuscitation, but face mask ventilation can be difficult. Compare supraglottic airway devices (SA) with face masks for term and late preterm infants receiving PPV immediately after birth. METHODS: Data sources include Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and Cumulative Index to Nursing and Allied Health Literature. Study selections include randomized, quasi-randomized, interrupted time series, controlled before-after, and cohort studies with English abstracts. Two authors independently extracted data and assessed risk of bias and certainty of evidence. The primary outcome was failure to improve with positive pressure ventilation. When appropriate, data were pooled using fixed effect models. RESULTS: Meta-analysis of 6 randomized controlled trials (1823 newborn infants) showed that use of an SA decreased the probability of failure to improve with PPV (relative risk 0.24; 95% confidence interval 0.17 to 0.36; P <.001, moderate certainty) and endotracheal intubation (4 randomized controlled trials, 1689 newborn infants) in the delivery room (relative risk 0.34, 95% confidence interval 0.20 to 0.56; P <.001, low certainty). The duration of PPV and time until heart rate >100 beats per minute was shorter with the SA. There was no difference in the use of chest compressions or epinephrine during resuscitation. Certainty of evidence was low or very low for most outcomes. CONCLUSIONS: Among late preterm and term infants who require resuscitation after birth, ventilation may be more effective if delivered by SA rather than face mask and may reduce the need for endotracheal intubation.

NETwork Meta-analysis Of Trials of Initial Oxygen in preterm Newborns (NETMOTION): A Protocol for Systematic Review and Individual Participant Data Network Meta-Analysis of Preterm Infants <32 Weeks' Gestation Randomized to Initial Oxygen Concentration for Resuscitation.

BACKGROUND: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of resuscitation of very and extremely preterm infants (<32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain. AIMS: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation. METHODS: We will conduct a systematic review and network meta-analysis using individual participant data. Studies of preterm infants <32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registries for eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (≤30%), intermediate (60%), and high (≥90%) oxygen. A two-step random-effects contrast-based network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality. DISCUSSION: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants <32 weeks' gestation.

Neurodevelopmental outcomes of preterm infants after randomisation to initial resuscitation with lower (FiO2 <0.3) or higher (FiO2 >0.6) initial oxygen levels. An individual patient meta-analysis.

OBJECTIVE: To determine the effects of lower (≤0.3) versus higher (≥0.6) initial fractional inspired oxygen (FiO2) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants <32 weeks' gestation. DESIGN: Meta-analysis of individual patient data from three randomised controlled trials. SETTING: Neonatal intensive care units. PATIENTS: 543 children <32 weeks' gestation. INTERVENTION: Randomisation at birth to resuscitation with lower (≤0.3) or higher (≥0.6) initial FiO2. OUTCOME MEASURES: Primary: death and/or NDI at 2 years of age.Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpO2) below or at/above 80%. RESULTS: By 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiO2 was not associated with difference in death and/or disability (difference (95% CI) -0.2%, -7% to 7%, p=0.96) or with cognitive scores <85 (2%, -5% to 9%, p=0.5). Five-minute SpO2 >80% was associated with decreased disability/death (14%, 7% to 21%) and cognitive scores >85 (10%, 3% to 18%, p=0.01). Multinomial regression analysis noted decreased death with 5-minute SpO2 ≥80% (odds (95% CI) 09.62, 0.98 to 0.96) and gestation (0.52, 0.41 to 0.65), relative to children without death or NDI. CONCLUSION: Initial FiO2 was not associated with difference in risk of disability/death at 2 years in infants <32 weeks' gestation but CIs were wide. Substantial benefit or harm cannot be excluded. Larger randomised studies accounting for patient differences, for example, gestation and gender are urgently needed.

Sustained Lung Inflations During Neonatal Resuscitation at Birth: A Meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation prioritized review of sustained inflation (SI) of the lung at birth. OBJECTIVE: To complete a systematic review and meta-analysis comparing strategies using 1 or more SI ≥1 second with intermittent inflations <1 second for newborns at birth. DATA SOURCES: Medline, Embase, and Evidence-Based Medicine Reviews were searched from January 1, 1946, to July 20, 2020. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages. DATA EXTRACTION: Reviewers extracted data, appraised risk of bias, and assessed certainty of evidence for each outcome. RESULTS: Ten trials enrolling 1502 preterm newborns were included. Five studies included newborns who did not receive assisted ventilation at the outset. There were no differences between SI and control groups for death before discharge or key morbidities. For death within the first 2 days, comparing SI with the controls, risk ratio was 2.42 (95% confidence interval = 1.15-5.09). In subgroup analysis of preterm infants ≤28 + 0 weeks' gestation, for death before discharge, risk ratio was 1.38 (95% confidence interval = 1.00-1.91). Together, these findings suggest the potential for harm of SI. LIMITATIONS: The certainty of evidence was very low for death in the delivery room and low for all other outcomes. CONCLUSIONS: In this systematic review, we did not find benefit in using 1 or more SI >5 seconds for preterm infants at birth. SI(s) may increase death before discharge among the subgroup born ≤28 + 0 weeks' gestation. There is insufficient evidence to determine the likely effect of SI(s) on other key morbidities.

Devices for Administering Ventilation at Birth: A Systematic Review.

CONTEXT: Positive pressure ventilation (PPV) is the most important intervention during neonatal resuscitation. OBJECTIVE: To compare T-piece resuscitators (TPRs), self-inflating bags (SIBs), and flow-inflating bags for newborns receiving PPV during delivery room resuscitation. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and trial registries (inception to December 2020). STUDY SELECTION: Randomized, quasi-randomized, interrupted time series, controlled before-and-after, and cohort studies were included without language restrictions. DATA EXTRACTION: Two researchers independently extracted data, assessed the risk of bias, and evaluated the certainty of evidence. The primary outcome was in-hospital mortality. When appropriate, data were pooled by using fixed-effect models. RESULTS: Meta-analysis of 4 randomized controlled trials (1247 patients) revealed no significant difference between TPR and SIB for in-hospital mortality (risk ratio 0.74; 95% confidence interval [CI] 0.40 to 1.34). Resuscitation with a TPR resulted in a shorter duration of PPV (mean difference -19.8 seconds; 95% CI -27.7 to -12.0 seconds) and lower risk of bronchopulmonary dysplasia (risk ratio 0.64; 95% CI 0.43 to 0.95; number needed to treat 32). No differences in clinically relevant outcomes were found in 2 randomized controlled trials used to compare SIBs with and without positive end-expiratory pressure valves. No studies used to evaluate flow-inflating bags were found. LIMITATIONS: Certainty of evidence was very low or low for most outcomes. CONCLUSIONS: Resuscitation with a TPR compared with an SIB reduces the duration of PPV and risk of bronchopulmonary dysplasia. A strong recommendation cannot be made because of the low certainty of evidence. There is insufficient evidence to determine the effectiveness of positive end-expiratory pressure valves when used with SIBs.