Part 5: Neonatal Resuscitation

These guidelines apply primarily to the “newly born” baby who is transitioning from the fluid-filled womb to the air-filled room. The “newly born” period extends from birth to the end of resuscitation and stabilization in the delivery area. However, the concepts in these guidelines may be applied to newborns during the neonatal period (birth to 28 days).

The primary goal of neonatal care at birth is to facilitate transition. The most important priority for newborn survival is the establishment of adequate lung inflation and ventilation after birth. Consequently, all newly born babies should be attended to by at least 1 person skilled and equipped to provide PPV. Other important goals include establishment and maintenance of cardiovascular and temperature stability as well as the promotion of mother-infant bonding and breast feeding, recognizing that healthy babies transition naturally.

The Neonatal Resuscitation Algorithm remains unchanged from 2015 and is the organizing framework for major concepts that reflect the needs of the baby, the family, and the surrounding team of perinatal caregivers.

Synopsis

Approximately 10% of newborns require assistance to breathe after birth.^1–3,5,13 Newborn resuscitation requires training, preparation, and teamwork. When the need for resuscitation is not anticipated, delays in assisting a newborn who is not breathing may increase the risk of death.^1,5,13 Therefore, every birth should be attended by at least 1 person whose primary responsibility is the newborn and who is trained to begin PPV without delay.^2–4

A risk assessment tool that evaluates risk factors present during pregnancy and labor can identify newborns likely to require advanced resuscitation; in these cases, a team with more advanced skills should be mobilized and present at delivery.^5,7 In the absence of risk stratification, up to half of babies requiring PPV may not be identified before delivery.^6,13

A standardized equipment checklist is a comprehensive list of critical supplies and equipment needed in a given clinical setting. In the birth setting, a standardized checklist should be used before every birth to ensure that supplies and equipment for a complete resuscitation are present and functional.^8,9,14,15

A predelivery team briefing should be completed to identify the leader, assign roles and responsibilities, and plan potential interventions. Team briefings promote effective teamwork and communication, and support patient safety.^8,10–12

Recommendation-Specific Supportive Text

1. A large observational study found that delaying PPV increases risk of death and prolonged hospitalization.¹ A systematic review and meta analysis showed neonatal resuscitation training reduced stillbirths and improved 7-day neonatal survival in low-resource countries.³ A retrospective cohort study demonstrated improved Apgar scores among high-risk newborns after neonatal resuscitation training.¹⁶
2. A multicenter, case-control study identified 10 perinatal risk factors that predict the need for advanced neonatal resuscitation.⁷ An audit study done before the use of risk stratification showed that resuscitation was anticipated in less than half of births requiring PPV.⁶ A prospective cohort study showed that risk stratification based on perinatal risk factors increased the likelihood of skilled team attendance at high-risk births.⁵
3. A multicenter quality improvement study demonstrated high staff compliance with the use of a neonatal resuscitation bundle that included briefing and an equipment checklist.⁸ A management bundle for preterm infants that included team briefing and equipment checks resulted in clear role assignments, consistent equipment checks, and improved thermoregulation and oxygen saturation.⁹
4. A single-center RCT found that role confusion during simulated neonatal resuscitation was avoided and teamwork skills improved by conducting a team briefing.¹¹ A statewide collaborative quality initiative demonstrated that team briefing improved team communication and clinical outcomes.¹⁰ A single-center study demonstrated that team briefing and an equipment checklist improved team communication but showed no improvement in equipment preparation.¹²

Synopsis

During an uncomplicated term or late preterm birth, it may be reasonable to defer cord clamping until after the infant is placed on the mother and assessed for breathing and activity. Early cord clamping (within 30 seconds) may interfere with healthy transition because it leaves fetal blood in the placenta rather than filling the newborn’s circulating volume. Delayed cord clamping is associated with higher hematocrit after birth and better iron levels in infancy.^9–21 While developmental outcomes have not been adequately assessed, iron deficiency is associated with impaired motor and cognitive development.^24–26 It is reasonable to delay cord clamping (longer than 30 seconds) in preterm babies because it reduces need for blood pressure support and transfusion and may improve survival.^1–8

There are insufficient studies in babies requiring PPV before cord clamping to make a recommendation.²² Early cord clamping should be considered for cases when placental transfusion is unlikely to occur, such as maternal hemorrhage or hemodynamic instability, placental abruption, or placenta previa.²⁷ There is no evidence of maternal harm from delayed cord clamping compared with early cord clamping.^{10–12,28–34} Cord milking is being studied as an alternative to delayed cord clamping but should be avoided in babies less than 28 weeks’ gestational age, because it is associated with brain injury.²³

Recommendation-Specific Supportive Text

1. Compared with preterm infants receiving early cord clamping, those receiving delayed cord clamping were less likely to receive medications for hypotension in a meta-analysis of 6 RCTs^1–6 and receive transfusions in a meta-analysis of 5 RCTs.⁷ Among preterm infants not requiring resuscitation, delayed cord clamping may be associated with higher survival than early cord clamping is.⁸ Ten RCTs found no difference in postpartum hemorrhage rates with delayed cord clamping versus early cord clamping.^{10–12,28–34}
2. Compared with term infants receiving early cord clamping, term infants receiving delayed cord clamping had increased hemoglobin concentration within the first 24 hours and increased ferritin concentration in the first 3 to 6 months in meta-analyses of 12 and 6 RCTs,^9–21 respectively. Compared with term and late preterm infants receiving early cord clamping, those receiving delayed cord clamping showed no significant difference in mortality, admission to the neonatal intensive care unit, or hyperbilirubinemia leading to phototherapy in metaanalyses of 4,^10,13,29,35 10,^{10,12,17,19,21,28,31,34,36,37} and 15 RCTs, respectively.^{9,12,14,18–21,28–30,32–34,38,39} Compared with term infants receiving early cord clamping, those receiving delayed cord clamping had increased polycythemia in metaanalyses of 13^{10,11,13,14,17,18,21,29,30,33,39–41} and 8 RCTs,^{9,10,13,19,20,28,30,34} respectively
3. For infants requiring PPV at birth, there is currently insufficient evidence to recommend delayed cord clamping versus early cord clamping.
4. A large multicenter RCT found higher rates of intraventricular hemorrhage with cord milking in preterm babies born at less than 28 weeks’ gestational age.²³

After birth, the newborn's heart rate is used to assess the effectiveness of spontaneous respiratory effort, the need for interventions, and the response to interventions. In addition, accurate, fast, and continuous heart rate assessment is necessary for newborns in whom chest compressions are initiated. Therefore, identifying a rapid and reliable method to measure the newborn's heart rate is critically important during neonatal resuscitation.

Synopsis

Auscultation of the precordium remains the preferred physical examination method for the initial assessment of the heart rate.⁹ Pulse oximetry and ECG remain important adjuncts to provide continuous heart rate assessment in babies needing resuscitation.

ECG provides the most rapid and accurate measurement of the newborn’s heart rate at birth and during resuscitation. Clinical assessment of heart rate by auscultation or palpation may be unreliable and inaccurate.^1–4 Compared to ECG, pulse oximetry is both slower in detecting the heart rate and tends to be inaccurate during the first few minutes after birth.^5,6,10–12 Underestimation of heart rate can lead to potentially unnecessary interventions. On the other hand, overestimation of heart rate when a newborn is bradycardic may delay necessary interventions. There are limited data comparing the different approaches to heart rate assessment during neonatal resuscitation on other neonatal outcomes. Use of ECG for heart rate detection does not replace the need for pulse oximetry to evaluate oxygen saturation or the need for supplemental oxygen.

Recommendation-Specific Supportive Text

1. In one RCT and one observational study, there were no reports of technical difficulties with ECG monitoring during neonatal resuscitation, supporting its feasibility as a tool for monitoring heart rate during neonatal resuscitation.^6,7
2. One observational study compared neonatal outcomes before (historical cohort) and after implementation of ECG monitoring in the delivery room.⁸ Compared with the newborns in the historical cohort, newborns with the ECG monitoring had lower rates of endotracheal intubation and higher 5-minute Apgar scores. However, newborns with ECG monitoring also had higher odds of receiving chest compressions in the delivery room.
3. Very low-quality evidence from 8 nonrandomized studies^{2,5,6,10,12–15} enrolling 615 newborns and 2 small RCTs^7,16 suggests that at birth, ECG is faster and more accurate for newborn heart assessment compared with pulse oximetry.
4. Very low-quality evidence from 2 nonrandomized studies and 1 randomized trial show that auscultation is not as accurate as ECG for heart rate assessment during newborn stabilization immediately after birth.^2–4

Synopsis

When chest compressions are initiated, an ECG should be used to confirm heart rate. When ECG heart rate is greater than 60/min, a palpable pulse and/or audible heart rate rules out pulseless electric activity.^17–21

Recommendation-Specific Supportive Text

1. Given the evidence for ECG during initial steps of PPV, expert opinion is that ECG should be used when providing chest compressions.

The vast majority of newborns breathe spontaneously within 30 to 60 seconds after birth, sometimes after drying and tactile stimulation.¹ Newborns who do not breathe within the first 60 seconds after birth or are persistently bradycardic (heart rate less than 100/min) despite appropriate initial actions (including tactile stimulation) may receive PPV at a rate of 40 to 60/min.^2,3 The order of resuscitative procedures in newborns differs from pediatric and adult resuscitation algorithms. On the basis of animal research, the progression from primary apnea to secondary apnea in newborns results in the cessation of respiratory activity before the onset of cardiac failure.⁴ This cycle of events differs from that of asphyxiated adults, who experience concurrent respiratory and cardiac failure. For this reason, neonatal resuscitation should begin with PPV rather than with chest compressions.^2,3 Delays in initiating ventilatory support in newly born infants increase the risk of death.¹

Synopsis

During an uncomplicated delivery, the newborn transitions from the low oxygen environment of the womb to room air (21% oxygen) and blood oxygen levels rise over several minutes. During resuscitation, supplemental oxygen may be provided to prevent harm from inadequate oxygen supply to tissues (hypoxemia).⁴ However, overexposure to oxygen (hyperoxia) may be associated with harm.⁵

Term and late preterm newborns have lower shortterm mortality when respiratory support during resuscitation is started with 21% oxygen (air) versus 100% oxygen.¹ No difference was found in neurodevelopmental outcome of survivors.¹ During resuscitation, pulse oximetry may be used to monitor oxygen saturation levels found in healthy term infants after vaginal birth at sea level.³

In more preterm newborns, there were no differences in mortality or other important outcomes when respiratory support was started with low (50% or less) versus high (greater than 50%) oxygen concentrations.² Given the potential for harm from hyperoxia, it may be reasonable to start with 21% to 30% oxygen. Pulse oximetry with oxygen targeting is recommended in this population.³

Recommendation-Specific Supportive Text

1. A meta-analysis of 5 randomized and quasirandomized trials enrolling term and late preterm newborns showed no difference in rates of hypoxic-ischemic encephalopathy (HIE). Similarly, meta-analysis of 2 quasi-randomized trials showed no difference in moderate-to-severe neurodevelopmental impairment at 1 to 3 years of age¹ for newborns administered 21% versus 100% oxygen.¹
2. Meta-analysis of 10 randomized trials enrolling preterm newborns, including subanalysis of 7 trials reporting outcomes for newborns 28 weeks’ gestational age or less, showed no difference in short-term mortality when respiratory support was started with low compared with high oxygen.²In the included studies, low oxygen was generally 21% to 30% and high oxygen was always 60% to 100%. Furthermore, no differences were found in long-term mortality, neurodevelopmental outcome, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, or major cerebral hemorrhage.²In a systematic review of 8 trials that used oxygen saturation targeting as a cointervention, all preterm babies in whom respiratory support was initiated with 21% oxygen (air) required supplemental oxygen to achieve the predetermined oxygen saturation target.²The recommendation to initiate respiratory support with a lower oxygen concentration reflects a preference to avoid exposing preterm newborns to additional oxygen (beyond what is necessary to achieve the predetermined oxygen saturation target) without evidence demonstrating a benefit for important outcomes.³
3. Meta-analysis of 7 randomized and quasi-randomized trials enrolling term and late preterm newborns showed decreased short-term mortality when using 21% oxygen compared with 100% oxygen for delivery room resuscitation.¹No studies looked at starting with intermediate oxygen concentrations (ie, 22% to 99% oxygen).

Synopsis

Babies who have failed to respond to PPV and chest compressions require vascular access to infuse epinephrine and/or volume expanders. In the delivery room setting, the primary method of vascular access is umbilical venous catheterization. Outside the delivery room, or if intravenous access is not feasible, the intraosseous route may be a reasonable alternative, determined by the local availability of equipment, training, and experience.

Recommendation-Specific Supportive Text

1. Umbilical venous catheterization has been the accepted standard route in the delivery room for decades.² There are no human neonatal studies to support one route over others.¹
2. There are 6 case reports indicating local complications of intraosseous needle placement.^3–8
3. Practitioners outside of the delivery room setting, and when umbilical venous catheterization is not feasible, may secure vascular access with the intraosseous route

*In this situation, “intravascular” means intravenous or intraosseous. Intra-arterial epinephrine is not recommended.

Synopsis

Medications are rarely needed in resuscitation of the newly born infant because low heart rate usually results from a very low oxygen level in the fetus or inadequate lung inflation after birth. Establishing ventilation is the most important step to correct low heart rate. However, if heart rate remains less than 60/min after ventilating with 100% oxygen (preferably through an endotracheal tube) and chest compressions, administration of epinephrine is indicated.

Administration of epinephrine via a low-lying umbilical venous catheter provides the most rapid and reliable medication delivery. The intravenous dose of epinephrine is 0.01 to 0.03 mg/kg, followed by a normal saline flush.⁴ If umbilical venous access has not yet been obtained, epinephrine may be given by the endotracheal route in a dose of 0.05 to 0.1 mg/kg. The dosage interval for epinephrine is every 3 to 5 minutes if the heart rate remains less than 60/min, although an intravenous dose may be given as soon as umbilical access is obtained if response to endotracheal epinephrine has been inadequate.

Recommendation-Specific Supportive Text

1. The very limited observational evidence in human infants does not demonstrate greater efficacy of endotracheal or intravenous epinephrine; however, most babies received at least 1 intravenous dose before ROSC.^1,2 In a perinatal model of cardiac arrest using term lambs undergoing transition with asphyxia-induced cardiopulmonary arrest, central venous epinephrine was associated with shorter time to ROSC and higher rates of ROSC than endotracheal epinephrine was.³ Intravenous epinephrine followed by a normal saline flush improves medication delivery.⁴
2. One very limited observational study (human) showed 0.03 mg/kg to be an inadequate endotracheal dose.¹ In the perinatal model of cardiac arrest, peak plasma epinephrine concentrations in animals were higher and were achieved sooner after central or low-lying umbilical venous administration compared with the endotracheal route, despite a lower intravenous dose (0.03 mg/ kg intravenous versus 0.1 mg/kg endotracheal route).³
3. In one very limited observational study, most infants who received an endotracheal dose achieved ROSC after a subsequent intravenous dose.² Although the more rapid response to intravenous epinephrine warrants its immediate administration once umbilical access is obtained, repetitive endotracheal doses or higher intravenous doses may result in potentially harmful plasma levels that lead to associated hypertension and tachycardia.^5–8
4. In one very limited observational study, many infants received multiple doses of epinephrine before ROSC.² The perinatal model of cardiac arrest documented peak plasma epinephrine concentrations at 1 minute after intravenous administration, but not until 5 minutes after endotracheal administration.³

Synopsis

A newly born infant in shock from blood loss may respond poorly to the initial resuscitative efforts of ventilation, chest compressions, and/or epinephrine. History and physical examination findings suggestive of blood loss include a pale appearance, weak pulses, and persistent bradycardia (heart rate less than 60/min). Blood may be lost from the placenta into the mother’s circulation, from the cord, or from the infant.

When blood loss is suspected in a newly born infant who responds poorly to resuscitation (ventilation, chest compressions, and/or epinephrine), it may be reasonable to administer a volume expander without delay. Normal saline (0.9% sodium chloride) is the crystalloid fluid of choice. Uncrossmatched type O, Rh-negative blood (or crossmatched, if immediately available) is preferred when blood loss is substantial.^4,5 An initial volume of 10 mL/kg over 5 to 10 minutes may be reasonable and may be repeated if there is inadequate response. The recommended route is intravenous, with the intraosseous route being an alternative.

Recommendation-Specific Supportive Text

1. There is no evidence from randomized trials to support the use of volume resuscitation at delivery. One large retrospective review found that 0.04% of newborns received volume resuscitation in the delivery room, confirming that it is a relatively uncommon event.¹ Those newborns who received volume resuscitation in the delivery room had lower blood pressure on admission to the neonatal intensive care unit compared with those who did not, indicating that factors other than blood loss may be important.¹
2. There is insufficient clinical evidence to determine what type of volume expander (crystalloid or blood) is more beneficial during neonatal resuscitation. Extrapolation from studies in hypotensive newborns shortly after birth^6–8 and studies in animals (piglets) support the use of crystalloid over albumin expanders⁵ and blood over crystalloid solutions.⁴ One review discussed recommendations for the use of volume expanders.²

Synopsis

Newly born infants who receive prolonged PPV or advanced resuscitation (eg, intubation, chest compressions ± epinephrine) should be closely monitored after stabilization in a neonatal intensive care unit or a monitored triage area because these infants are at risk for further deterioration.

Infants 36 weeks’ or greater estimated gestational age who receive advanced resuscitation should be examined for evidence of HIE to determine if they meet criteria for therapeutic hypothermia. Therapeutic hypothermia is provided under defined protocols similar to those used in published clinical trials and in facilities capable of multidisciplinary care and longitudinal follow-up. The impact of therapeutic hypothermia on infants less than 36 weeks’ gestational age with HIE is unclear and is a subject of ongoing research trials.

Hypoglycemia is common in infants who have received advanced resuscitation and is associated with poorer outcomes.⁸ These infants should be monitored for hypoglycemia and treated appropriately.

Infants with unintentional hypothermia (temperature less than 36°C) immediately after stabilization should be rewarmed to avoid complications associated with low body temperature (including increased mortality, brain injury, hypoglycemia, and respiratory distress). Evidence suggests that warming can be done rapidly (0.5°C/h) or slowly (less than 0.5°C/h) with no significant difference in outcomes.^15–19 Caution should be taken to avoid overheating.

Recommendation-Specific Supportive Text

1. In a meta-analysis of 8 RCTs involving 1344 term and late preterm infants with moderate-to-severe encephalopathy and evidence of intrapartum asphyxia, therapeutic hypothermia resulted in a significant reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (odds ratio 0.75; 95% CI, 0.68–0.83).¹
2. Newly born infants who required advanced resuscitation are at significant risk of developing moderate-to-severe HIE^2–4 and other morbidities.^5–7
3. Newly born infants with abnormal glucose levels (both low and high) are at increased risk for brain injury and adverse outcomes after a hypoxic-ischemic insult.^8–14
4. Two small RCTs^16,19 and 4 observational studies^15,17,18,20 of infants with hypothermia after delivery room stabilization found no difference between rapid or slow rewarming for outcomes of mortality,^15,17 convulsions/seizures,¹⁹ intraventricular or pulmonary hemorrhage,^15,17,19,20 hypoglycemia,^16,17,19 or apnea.^16,17,19 One observational study found less respiratory distress in infants who were slowly rewarmed,¹⁸ while a separate study found less respiratory distress syndrome in infants who were rapidly rewarmed.¹⁷

Synopsis

Expert neonatal and bioethical committees have agreed that, in certain clinical conditions, it is reasonable not to initiate or to discontinue life-sustaining efforts while continuing to provide supportive care for babies and families.^1,2,4

If the heart rate remains undetectable and all steps of resuscitation have been completed, it may be reasonable to redirect goals of care. Case series show small numbers of intact survivors after 20 minutes of no detectable heart rate. The decision to continue or discontinue resuscitative efforts should be individualized and should be considered at about 20 minutes after birth. Variables to be considered may include whether the resuscitation was considered optimal, availability of advanced neonatal care (such as therapeutic hypothermia), specific circumstances before delivery, and wishes expressed by the family.^3,6

Some babies are so sick or immature at birth that survival is unlikely, even if neonatal resuscitation and intensive care are provided. In addition, some conditions are so severe that the burdens of the illness and treatment greatly outweigh the likelihood of survival or a healthy outcome. If it is possible to identify such conditions at or before birth, it is reasonable not to initiate resuscitative efforts. These situations benefit from expert consultation, parental involvement in decision-making, and, if indicated, a palliative care plan.^1,2,4–6

Recommendation-Specific Supportive Text

1. It is the expert opinion of national medical societies that conditions exist for which it is reasonable to not initiate resuscitation or to discontinue resuscitation once these conditions are identified.^1,2,4,5
2. Randomized controlled studies and observational studies in settings where therapeutic hypothermia is available (with very low certainty of evidence) describe variable rates of survival without moderate-to-severe disability in babies who achieve ROSC after 10 minutes or more despite continued resuscitation. None of these studies evaluate outcomes of resuscitation that extends beyond 20 minutes of age, by which time the likelihood of intact survival was very low. The studies were too heterogeneous to be amenable to meta-analysis.³
3. Conditions in which noninitiation or discontinuation of resuscitation may be considered include extremely preterm birth and certain severe congenital anomalies. National guidelines recommend individualization of parent-informed decisions based on social, maternal, and fetal/neonatal factors.^1,2,4 A systematic review showed that international guidelines variably described periviability between 22 and 24 weeks’ gestational age.⁷

Neonatal resuscitation science has advanced significantly over the past 3 decades, with contributions by many researchers in laboratories, in the delivery room, and in other clinical settings. While this research has led to substantial improvements in the Neonatal Resuscitation Algorithm, it has also highlighted that we still have more to learn to optimize resuscitation for both preterm and term infants. With growing enthusiasm for clinical studies in neonatology, elements of the Neonatal Resuscitation Algorithm continue to evolve as new evidence emerges.

The current guidelines have focused on clinical activities described in the resuscitation algorithm, rather than on the most appropriate devices for each step. Reviews in 2021 and later will address choice of devices and aids, including those required for ventilation (T-piece, self-inflating bag, flow-inflating bag), ventilation interface (face mask, laryngeal mask), suction (bulb syringe, meconium aspirator), monitoring (respiratory function monitors, heart rate monitoring, near infrared spectroscopy), feedback, and documentation.

Review of the knowledge chunks during this update identified numerous questions and practices for which evidence was weak, uncertain, or absent. The following knowledge gaps require further research:

Resuscitation Preparedness

• The frequency and format of booster training or refresher training that best supports retention of neonatal resuscitation knowledge, technical skills, and behavioral skills
• The effects of briefing and debriefing on team performance

During and Just After Delivery

• Optimal cord management strategies for various populations, including nonvigorous infants and those with congenital heart or lung disease
• Optimal management of nonvigorous infants with MSAF

Early Resuscitation

• The most effective device(s) and interface(s) for providing PPV
• Impact of routine use of the ECG during neonatal resuscitation on resuscitation
• Feasibility and effectiveness of new technologies for rapid heart rate measurement (such as electric, ultrasonic, or optical devices)
• Optimal oxygen management during and after resuscitation

Advanced Resuscitation

• Novel techniques for effective delivery of CPR, such as chest compressions accompanied by sustained inflation
• Optimal timing, dosing, dose interval, and delivery routes for epinephrine or other vasoactive drugs, including earlier use in very depressed newly born infants
• Indications for volume expansion, as well as optimal dosing, timing, and type of volume
• The management of pulseless electric activity

Specific Populations

• Management of the preterm newborn during and after resuscitation
• Management of congenital anomalies of the heart and lungs during and after resuscitation
• Resuscitation of newborns in the neonatal unit after the newly born period
• Resuscitation of newborns in other settings up to 28 days of age

Postresuscitation Care

• Optimal dose, route, and timing of surfactant in at-risk newborns, including less-invasive administration techniques
• Indications for therapeutic hypothermia in babies with mild HIE and in those born at less than 36 weeks' gestational age
• Adjunctive therapies to therapeutic hypothermia
• Optimal management of blood glucose
• Optimal rewarming strategy for newly born infants with unintentional hypothermia

For all these gaps, it is important that we have information on outcomes considered critical or important by both healthcare providers and families of newborn infants.

The research community needs to address the paucity of educational studies that provide outcomes with a high level of certainty. Internal validity might be better addressed by clearly defined primary outcomes, appropriate sample sizes, relevant and timed interventions and controls, and time series analyses in implementation studies. External validity might be improved by studying the relevant learner or provider populations and by measuring the impact on critical patient and system outcomes rather than limiting study to learner outcomes.

Researchers studying these gaps may need to consider innovations in clinical trial design; examples include pragmatic study designs and novel consent processes. As mortality and severe morbidities decline with biomedical advancements and improvements in healthcare delivery, there is decreased ability to have adequate power for some clinical questions using traditional individual patient randomized trials. Another barrier is the difficulty in obtaining antenatal consent for clinical trials in the delivery room. Adaptive trials, comparative effectiveness designs, and those using cluster randomization may be suitable for some questions, such as the best approach for MSAF in nonvigorous infants. High-quality observational studies of large populations may also add to the evidence. When feasible, well-designed multicenter randomized clinical trials are still optimal to generate the highest-quality evidence.

Finally, we wish to reinforce the importance of addressing the values and preferences of our key stakeholders, the families and teams who are involved in the process of resuscitation. Gaps in this domain, whether perceived or real, should be addressed at every stage in our research, educational, and clinical activities.

The American Heart Association requests that this document be cited as follows: Aziz K, Lee HC, Escobedo MB, Hoover AV, Kamath-Rayne BD, Kapadia VS, Magid DJ, Niermeyer S, Schmolzer GM, Szyld E, Weiner GM, Wyckoff MH, Yamada NK, Zaichkin J. Part 5: neonatal resuscitation: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142(suppl 2):S524–S550. doi: 10.1161/ CIR.0000000000000902

This article has been copublished in Pediatrics.