Effect of Breathing Support in Very Preterm Infants Not Breathing During Deferred Cord Clamping: A Randomized Controlled Trial (The ABC Study).

OBJECTIVE: To determine if providing respiratory support to very preterm infants who fail to breathe regularly during deferred cord clamping (DCC) decreased red cell transfusion. STUDY DESIGN: Infants less than 31 weeks of gestation undergoing DCC who were apneic or not breathing regularly at 15 seconds underwent stratified randomization. Pale, limp, and nonresponsive infants were excluded. The standard group received gentle stimulation in a neutral position for 50 seconds; the intervention group received intermittent positive pressure ventilation via face mask and T piece from 20 to 50 seconds of age with a fractional inspired oxygen of 0.3. The primary outcome was the proportion transfused, with a secondary composite outcome of death, severe intraventricular hemorrhage, or chronic lung disease. RESULTS: Of 311 assessed infants, 113 met the inclusion criteria and were studied; 57 received the intervention and 56 standard treatment. Patient characteristics were similar. Overall, 105 infants (93%) received the intended 50 seconds DCC (54 in the intervention group and 51 in the standard group). Rates of transfusion were similar (28% vs 30% in the intervention vs control groups), as were rates of the composite outcome (46% vs 38% in the intervention vs the control arms; P = .45). CONCLUSIONS: Providing breathing support during 50 seconds of DCC in this single-center cohort seemed to be safe and feasible, but did not decrease the transfusion rates or improve outcomes. TRIAL REGISTRATION: http://www.anzctr.org.au/ACTRN12615001026516.aspx.

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.

Australian and New Zealand Committee on Resuscitation Neonatal Resuscitation guidelines 2016.

New Australian and New Zealand Neonatal Resuscitation guidelines reflect recent advances in neonatal resuscitation science, as critically appraised by the International Liaison Committee on Resuscitation. Substantial changes since the 2010 guidelines include: (i) updates to the Newborn Resuscitation Flowchart to include a greater emphasis on maintaining normal body temperature, and to emphasise the importance of beginning assisted ventilation by 1 min in infants who have absent or ineffective spontaneous breathing; (ii) updates to the physiology of the normal perinatal transition that resuscitation is trying to restore; (iii) recommendations for more frequent reinforcement of training, and for structured feedback for resuscitation training instructors; (iv) new guidance in relation to the timing of cord clamping for preterm newborn infants; (v) recommendation to monitor body temperature on admission to newborn units as a resuscitation quality indicator; (vi) suggestion to consider electrocardiographic (ECG) monitoring (as an adjunct to oximetry) to obtain more rapid and accurate estimation of heart rate during resuscitation; (vii) removal of previous suggestions to intubate meconium-exposed, non-vigorous term infants to suction the trachea; and (viii) suggestion to establish vascular access to enable administration of intravenous adrenaline (epinephrine) as soon as chest compressions are deemed to be needed.

Fluid recovery during lung lavage in meconium aspiration syndrome.

UNLABELLED: Lung lavage using two aliquots of 15 mL/kg of dilute surfactant was performed in 30 ventilated infants with severe meconium aspiration syndrome (MAS). Mean recovery of instilled lavage fluid was 46%, with greater fluid return associated with lower mean airway pressure at 24 h and a shorter duration of respiratory support. CONCLUSION: Recovery of instilled lavage fluid is paramount in effective lung lavage in MAS and must be afforded priority in the lavage technique.

Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome.

OBJECTIVE: To evaluate whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS). STUDY DESIGN: We conducted a randomized controlled trial that enrolled ventilated infants with MAS. Infants randomized to lavage received two 15-mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, extracorporeal membrane oxygenation (ECMO). RESULTS: Sixty-six infants were randomized, with one ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 versus 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomization. CONCLUSION: Lung lavage with dilute surfactant does not alter duration of respiratory support, but may reduce mortality, especially in units not offering ECMO.

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.

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.

What to do if A + B doesn't work.

The majority of newborn resuscitations require very little beyond simple airway management and assisted ventilation. If cardiovascular collapse is serious enough to warrant additional support, resuscitation algorithms recommend moving to chest compressions and then on to medications and possibly volume replacement if vital signs remain marginal or absent. The evidence base upon which this part of the neonatal resuscitation algorithm is structured is sparse. Chest compressions and medications are rare interventions that do not lend themselves easily to clinical trials. Slowly but surely, however, the genesis of an empirical evidence base for this part of the algorithm is beginning to appear.

Hyperinsulinemia in cord blood in mothers with type 2 diabetes and gestational diabetes mellitus in New Zealand.

OBJECTIVE: In genetically diabetes-prone populations, maternal diabetes during pregnancy increases the risk of their children developing diabetes and obesity (the vicious cycle of type 2 diabetes). Fetal hyperinsulinemia at birth acts as a marker of this risk. We therefore examined whether cord insulin and leptin concentrations are increased in offspring of Maori and Pacific Island mothers with type 2 and gestational diabetes mellitus (GDM) and varying degrees of glycemic control (HbA(1c)). RESEARCH DESIGNS AND METHODS: Maori and Pacific Island mothers were prospectively recruited at Middlemore Hospital, South Auckland. Cord blood was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation to 138 mothers with GDM, 39 mothers with type 2 diabetes, and 95 control mothers. RESULTS: Babies born to mothers with both type 2 diabetes and GDM had higher birth weight and skinfold thickness and markedly higher concentrations of insulin (median [interquartile range] type 2 diabetes 77 pmol/l [42-143], GDM 67 pmol/l [42-235], and control subjects 33 pmol/l [18-62]; P < 0.001) and leptin (type 2 diabetes 39 ng/ml [18-75], GDM 31 ng/ml [17-58], and control subjects 13 ng/ml [8-22]; P < 0.001) in cord blood. Cord insulin concentrations >120 pmol/l were found in 29% of offspring of mothers with GDM and 31% of mothers with type 2 diabetes. Many mothers with GDM had abnormalities of glucose tolerance postpartum (20% type 2 diabetes, 34% impaired glucose tolerance or impaired fasting glucose). Higher cord insulin (57 pmol/l [40-94]) and leptin (26 ng/ml [17-39]) concentrations were found even in offspring of GDM mothers with normal glucose tolerance postpartum. CONCLUSIONS: Raised cord insulin and leptin concentrations are a common finding in offspring of mothers with type 2 diabetes and GDM in this population.

Factors modulating effective chest compressions in the neonatal period.

The need for chest compressions in the newborn is a rare occurrence. The methods employed for delivery of chest compressions have been poorly researched. Techniques that have been studied include compression:ventilation ratios, thumb versus finger method of delivering compressions, depth of compression, site on chest of compression, synchrony or asynchrony of breaths with compressions, and modalities to improve the compression technique and consistency. Although still in its early days, an evidence-based guideline for chest compressions is beginning to take shape.

Delayed cord clamping and blood flow in the superior vena cava in preterm infants: an observational study.

OBJECTIVE: To determine if timing of cord clamping affects blood flow in the upper body, as measured by flow in the superior vena cava (SVC). DESIGN: Observational study. SETTING: Neonatal Unit, Middlemore Hospital, Auckland, New Zealand. PATIENTS: 30 preterm infants <30 weeks' gestational age. INTERVENTION: Cord clamping was immediate in 17 infants and delayed by 30-45 s in 13. RESULTS: Infants in the two groups did not differ significantly in terms of gestational age, gender or use of antenatal steroids. Median flow in the SVC in the first 24 h was significantly higher in the group with delayed clamping (median 91 ml/kg/min; IQR 81-101) compared with 52 ml/kg/min (IQR 42-100) in the immediate clamping group (p=0.028). Fewer infants in the delayed group had low flow (1 compared with 9; p=0.017). All three infants with intraventricular haemorrhage (IVH) (of any grade) had low flow. CONCLUSIONS: Blood flow in the SVC was higher in infants where delayed cord clamping was performed. The relationship of IVH, low flow and timing of cord clamping requires further study.

Effects of prophylactic indomethacin in extremely low-birth-weight infants with and without adequate exposure to antenatal corticosteroids.

OBJECTIVE: To examine whether treatment with antenatal corticosteroids modifies the immediate and long-term effects of prophylactic indomethacin sodium trihydrate in extremely low-birth-weight infants. DESIGN: Post hoc subgroup analysis of data from the Trial of Indomethacin Prophylaxis in Preterms. SETTING: Thirty-two neonatal intensive care units in Canada, the United States, Australia, New Zealand, and Hong Kong. PARTICIPANTS: A total of 1195 infants with birth weights of 500 to 999 g and known exposure to antenatal corticosteroids. We defined as adequate any exposure to antenatal corticosteroids that occurred at least 24 hours before delivery. INTERVENTION: Indomethacin or placebo intravenously once daily for the first 3 days. OUTCOME MEASURES: Death or survival to 18 months with cerebral palsy, cognitive delay, severe hearing loss, or bilateral blindness; severe periventricular and intraventricular hemorrhage; patent ductus arteriosus; and surgical closure of a patent ductus arteriosus. RESULTS: Of the 1195 infants in this analysis cohort, 670 had adequate and 525 had inadequate exposure to antenatal corticosteroids. There was little statistical evidence of heterogeneity in the effects of prophylactic indomethacin between the subgroups for any of the outcomes. The adjusted P values for interaction were as low as .15 for the outcome of death or impairment at 18 months and as high as .80 for the outcome of surgical duct closure. CONCLUSION: We find little evidence that the effects of prophylactic indomethacin vary in extremely low-birth-weight infants with and without adequate exposure to antenatal corticosteroids. Trial Registration clinicaltrials.gov Identifier: NCT00009646.

Repeat prenatal corticosteroid doses do not alter neonatal blood pressure or myocardial thickness: randomized, controlled trial.

OBJECTIVE: The goal was to determine whether repeat prenatal corticosteroid treatment alters blood pressure and myocardial wall thickness in neonates. METHODS: A randomized, double-blind, placebo-controlled trial was performed in a tertiary perinatal center. Mothers with a singleton, twin, or triplet pregnancy, at a gestational age of <32 weeks, who had received initial treatment with corticosteroid > or =7 days earlier and who were considered to be at continued risk of preterm birth were assigned randomly to receive additional weekly betamethasone or placebo treatment. One hundred forty-five infants born to 120 women were studied. Blood pressure in the first 4 weeks after birth or until hospital discharge and interventricular septal thickness and left ventricular posterior wall thickness in diastole 48 to 72 hours after birth were measured. RESULTS: There were no differences in mean, systolic, or diastolic blood pressures between infants in the placebo and repeat steroid groups. Blood pressures of infants in both groups were similar to published normal values. There were no differences between groups in interventricular septal thickness or left ventricular posterior wall thickness in diastole. In comparison with published normal ranges, however, 24% of infants had interventricular septal thickness and 32% of infants had left ventricular posterior wall thickness of >95th percentile. CONCLUSION: Exposure to repeat prenatal corticosteroid treatment did not increase neonatal blood pressure or myocardial wall thickness in infants who remained at risk of very preterm birth > or =7 days after an initial course of corticosteroid treatment.