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.

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.

Outcomes of delivery room resuscitation of bradycardic preterm infants: A retrospective cohort study of randomised trials of high vs low initial oxygen concentration and an individual patient data analysis.

OBJECTIVE: To determine whether hospital mortality (primary outcome) is associated with duration of bradycardia without chest compressions during delivery room (DR) resuscitation in a retrospective cohort study of randomized controlled trials (RCTs) in preterm infants assigned low versus high initial oxygen concentration. METHODS: Medline and EMBASE were searched from 01/01/1990 to 12/01/2020. RCTs of low vs high initial oxygen concentration which recorded serial heart rate (HR) and oxygen saturation (SpO2) during resuscitation of infants <32 weeks gestational age were eligible. Individual patient level data were requested from the authors. Newborns receiving chest compressions in the DR and those with no recorded HR in the first 2 min after birth were excluded. Prolonged bradycardia (PB) was defined as HR < 100 bpm for ≥2 min. Individual patient data analysis and pooled data analysis were conducted. RESULTS: Data were collected from 720 infants in 8 RCTs. Neonates with PB had higher odds of hospital death before [OR 3.8 (95% CI 1.5, 9.3)] and after [OR 1.7 (1.2, 2.5)] adjusting for potential confounders. Bradycardia occurred in 58% infants, while 38% had PB. Infants with bradycardia were more premature and had lower birth weights. The incidence of bradycardia in infants resuscitated with low (≤30%) and high (≥60%) oxygen was similar. Neonates with both, PB and SpO2 < 80% at 5 min after birth had higher odds of hospital mortality. [OR 18.6 (4.3, 79.7)]. CONCLUSION: In preterm infants who did not receive chest compressions in the DR, prolonged bradycardia is associated with hospital mortality.

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.

Pediatric timing of epinephrine doses: A systematic review.

AIM: To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest. METHODS: We searched Medline, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL) for human randomized clinical trials and observational studies including comparative cohorts. Two investigators reviewed relevance of studies, extracted the data, conducted meta-analyses and assessed the risk of bias using the GRADE and CLARITY frameworks. Authors of the eligible studies were contacted to obtain additional data. Critically important outcomes included return of spontaneous circulation, survival to hospital discharge and survival with good neurological outcome. RESULTS: We identified 7 observational studies suitable for meta-analysis and no randomized clinical trials. The overall certainty of evidence was very low. For the critically important outcomes, the earlier administration of epinephrine was favorable for both in-hospital and out-of-hospital cardiac arrest. Because of a limited number of eligible studies and the presence of severe confounding factors, we could not determine the optimal interval of epinephrine administration. CONCLUSIONS: Earlier administration of the first epinephrine dose could be more favorable in non-shockable pediatric cardiac arrest. The optimal interval for epinephrine administration remains unclear.

Effect of opaque wraps for pulse oximeter sensors: randomised cross-over trial.

BACKGROUND: Evidence is lacking as to whether ambient light or phototherapy light could interfere with pulse oximeter performance. METHODS: In this randomised cross-over trial, we recruited neonates of gestation >24 weeks. Consented infants were randomly assigned to either pulse oximeter sensor with opaque wrap or without opaque wrap. Nellcor and Masimo sensors were applied simultaneously to different feet for 10 min of recording. Infants were crossed over to the other intervention for a further 10 min, totalling 20 min recording per infant. Primary outcome was faster acquisition of data with shielding of pulse oximeter sensor as compared with not shielding. RESULTS: A total of 96 babies were recruited. There was no difference in primary outcome of time taken to display valid data between the two groups (opaque wrap: 12.73±3.1 s vs no opaque wrap: 13.16±3.3 s, p=0.27). There was no difference in any of the secondary outcomes (percentage of valid data points, percentage of time saturation below target, and so on) between the two groups in both pulse oximeters. Masimo sensor readings displayed a higher mean oxygen saturation (mean difference of 2.85, p=0.001) and lower percentage of time saturation below 94% (mean difference of -27.8, p=0.001) than Nellcor in both groups. There was no difference in any of the outcomes in babies receiving phototherapy (n=21). CONCLUSION: In this study, shielding the pulse oximeter sensor from ambient light or phototherapy light did not yield faster data acquisition or better data quality. TRIAL REGISTRATION NUMBER: ISRCTN10302534.

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.

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.

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.

The Route, Dose, and Interval of Epinephrine for Neonatal Resuscitation: A Systematic Review.

CONTEXT: Current International Liaison Committee on Resuscitation recommendations on epinephrine administration during neonatal resuscitation were derived in 2010 from indirect evidence in animal or pediatric studies. OBJECTIVE: Systematic review of human infant and relevant animal studies comparing other doses, routes, and intervals of epinephrine administration in neonatal resuscitation with (currently recommended) administration of 0.01 to 0.03 mg/kg doses given intravenously (IV) every 3 to 5 minutes. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and trial registry databases. STUDY SELECTION: Predefined criteria were used for selection. DATA EXTRACTION: Risk of bias was assessed by using published tools appropriate for the study type. Certainty of evidence was assessed by using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Only 2 of 4 eligible cohort studies among 593 unique retrieved records yielded data allowing comparisons. There were no differences between IV and endotracheal epinephrine for the primary outcome of death at hospital discharge (risk ratio = 1.03 [95% confidence interval 0.62 to 1.71]) or for failure to achieve return of spontaneous circulation, time to return of spontaneous circulation (1 study; 50 infants), or proportion receiving additional epinephrine (2 studies; 97 infants). There were no differences in outcomes between 2 endotracheal doses (1 study). No human infant studies were found in which authors addressed IV dose or dosing interval. LIMITATIONS: The search yielded sparse human evidence of very low certainty (downgraded for serious risk of bias and imprecision). CONCLUSIONS: Administration of epinephrine by endotracheal versus IV routes resulted in similar survival and other outcomes. However, in animal studies, researchers continue to suggest benefit of IV administration using currently recommended doses.

Duration of Resuscitation at Birth, Mortality, and Neurodevelopment: A Systematic Review.

CONTEXT: The International Liaison Committee on Resuscitation Neonatal Life Support Task Force reviewed evidence for the duration of cardiopulmonary resuscitation (CPR) for newborns immediately after birth. OBJECTIVE: To summarize evidence for ongoing CPR on the outcomes of survival, neurodevelopment, and the composite of survival without moderate or severe neurodevelopmental impairment (NDI). DATA SOURCES: Medline, Embase, Evidence-Based Medicine Reviews, Cumulative Index to Nursing and Allied Health Literature, and Scientific Electronic Library Online were searched between inception and February 29, 2020. STUDY SELECTION: Two independent reviewers selected studies of newborns with at least 10 minutes of asystole, bradycardia, or pulseless electrical activity for which CPR is indicated. DATA EXTRACTION: Two independent reviewers extracted data and appraised the risk of bias. RESULTS: In 16 eligible studies, researchers reported outcomes of 579 newborns born between 1982 and 2017. Within individual studies, 2% to 100% of infants survived to last follow-up (hospital discharge through 12 years). Summarized across studies, 237 of 579 (40.9%) newborns survived to last follow-up. In 13 studies, researchers reported neurodevelopmental outcomes of 277 newborns. Of these, 30 of 277 (10.8%) survived without moderate or severe impairment, and 240 of 277 (87%) met the composite outcome of death or NDI (191 died and 49 survived with moderate or severe impairment). LIMITATIONS: There was very low certainty of evidence because of risk of bias and inconsistency. CONCLUSIONS: Infants with ongoing CPR at 10 minutes after birth are at high risk for mortality and neurodisability, but survival without moderate or severe NDI is possible. One specified duration of CPR is unlikely to uniformly predict survival or survival without neuroimpairment.

Tracheal suctioning of meconium at birth for non-vigorous infants: a systematic review and meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation sought to review the initial management of non-vigorous newborns delivered through meconium stained amniotic fluid (MSAF). OBJECTIVE: To complete a systematic review and meta-analysis comparing endotracheal intubation and suctioning to immediate resuscitation without intubation for non-vigorous infants born at ≥34 weeks gestation delivered through MSAF. DATA SOURCES: Medline, EMBASE, the Cochrane Database of Systematic Reviews, and other registries were searched from 1966 to November 7, 2019. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages. DATA EXTRACTION: Reviewers extracted data, appraised risk of bias, and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence for each outcome. RESULTS: Four randomized controlled trials (RCTs) included 581 patients and one observational study included 231 patients. No significant differences were observed between the group treated with tracheal suctioning compared with immediate resuscitation for survival at discharge (4 RCTs; risk ratio [RR] = 1.01; 95 % CI, 0.96-1.06; p = 0.69; observational study; no deaths), hypoxic ischemic encephalopathy and meconium aspiration syndrome. LIMITATIONS: The certainty of evidence was low for survival at discharge and very low for all other outcomes. CONCLUSIONS: For non-vigorous newborns delivered through MSAF, there is insufficient evidence to suggest routine immediate direct laryngoscopy with tracheal suctioning. PROSPERO: CRD42019122778. CLINICAL TRIALS REGISTRATION: PROSPERO; CRD42019122778.

Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants.

Introduction: Extremely premature infants are susceptible to fluctuations in cerebral blood flow due to immaturity of cerebral autoregulation. Inotropes may cause rapid changes to systemic blood pressure and consequently cerebral blood flow, especially within the first 72 hours of life. This period is recognized to carry the greatest risk for cerebral hemorrhage. This study evaluates the incidence of death and/or severe brain injury in extremely preterm infants treated with inotropes in the first 72 hours of life.Methods: Prospective cohort study of infants born ≤29+0 weeks gestational age (GA) between January 2013 and December 2016. Severe brain injury was defined based on head ultrasound as presence of: grade III or IV intraventricular hemorrhage (IVH), moderate to severe post-hemorrhagic ventricular dilatation (PHVD), or cystic periventricular leukomalacia (cPVL). The association between inotrope use and death and/or brain injury was explored via logistic regression controlling for predefined confounding risk factors.Results: Of 497 eligible infants, 97 (19.5%) received inotropes during the first 72 hours. GA at birth, birth weight (BW), and 5-minute Apgar scores were lower among infants who received early inotropes compared to those not treated with inotropes. A stepwise logistic regression of the predefined confounding factors showed GA, exposure for antenatal steroids, and admission hypothermia to be significant confounding factors. Adjusting for those factors, early use of inotropes was associated with increased risk of death and/or severe brain injury (AOR 4.5; 95%CI: 2.4-8.5), severe brain injury (AOR 4.2; 95% CI: 1.9-8.9), and IVH of any grade (AOR 2.9; 95%CI: 1.7-4.9).Conclusion: Early inotropes use was associated with higher risk of death and/or severe brain injury. Strict indications and strategies for minimizing inotrope use while preventing hypotension should be implemented in the early postnatal care of infants at risk for severe brain injury.

Association of Deferred vs Immediate Cord Clamping With Severe Neurological Injury and Survival in Extremely Low-Gestational-Age Neonates.

Importance: Deferred cord clamping (DCC) is recommended for term and preterm neonates to reduce neonatal complications. Information on the association of DCC with outcomes for extremely low-gestational-age neonates is limited. Objective: To compare neonatal outcomes after DCC and immediate cord clamping (ICC) in extremely low-gestational-age neonates. Design, Setting, and Participants: In this retrospective cohort study, eligible neonates born between January 1, 2011, and December 31, 2015, were divided into 2 groups: DCC and ICC. Neonates were recruited from tertiary neonatal intensive care units participating in the Canadian Neonatal Network, and analysis began in January 2018. Neonates were eligible if they were born at 22 to 28 weeks' gestational age and admitted to a participating Canadian Neonatal Network neonatal intensive care unit during the study period. Neonates who were born outside a tertiary-level neonatal intensive care unit, were moribund at birth, needed palliative care before delivery, had major congenital anomalies, or lacked cord clamping information were excluded. Main Outcomes and Measures: Composite of severe neurological injury (intraventricular hemorrhage grade ≥3 with or without persistent periventricular echogenicity) or mortality before discharge. Results: Of 8221 admitted neonates, 4680 were included in the study, of whom 1852 (39.6%) received DCC and 2828 (60.4%) received ICC. There were 974 (52.7%) male neonates in the DCC group and 1540 (54.5%) male neonates in the ICC group. Median (interquartile range) gestational age was 27 (25-28) weeks for the DCC group and 26 (25-27) weeks for the ICC group. Median (interquartile range) birth weight was 930 (760-1120) g and 870 (700-1060) g for DCC and ICC groups, respectively. Neonates who received DCC had significantly reduced odds of the composite outcome of severe neurological injury or mortality (adjusted odds ratio [AOR], 0.80; 95% CI, 0.67-0.96), mortality (AOR, 0.74; 95% CI, 0.59-0.93), and severe neurological injury (AOR, 0.80; 95% CI, 0.64-0.99). The odds of bronchopulmonary dysplasia (AOR, 1.00; 95% CI, 0.84-1.19), retinopathy of prematurity stage 3 or higher (AOR, 0.94; 95% CI, 0.71-1.25), necrotizing enterocolitis stage 2 or higher (AOR, 0.86; 95% CI, 0.66-1.12), late-onset sepsis (AOR, 1.02; 95% CI, 0.85-1.22), and receipt of 2 or more blood transfusions (AOR, 0.93; 95% CI, 0.79-1.10) did not differ between the groups. Propensity score-matched analyses revealed lower odds of mortality (AOR, 0.79; 95% CI, 0.65-0.95), late-onset sepsis (AOR, 0.81; 95% CI, 0.69-0.95), and treatment for hypotension (AOR, 0.75; 95% CI, 0.60-0.95) in the DCC group. Conclusions and Relevance: In this study of extremely low-gestational-age neonates who received DCC or ICC, DCC was associated with reduced risk for the composite outcome of severe neurological injury or mortality.