Oxygen during Neonatal Resuscitation: Too Much versus Too Little, Does It Matter?

Abstract

Background

Oxygen has been a key component of neonatal resuscitation for nearly two centuries. Based on clinical trials that demonstrated worse outcomes when neonatal resuscitation was initiated with 100% oxygen, there was a change in approach to using 21% oxygen at the initiation of ventilation for newborns at birth. However, for extremely preterm newborns, lower oxygen levels lead to early hypoxia and bradycardia, leading to higher rates of severe intraventricular hemorrhage and death. The balance between hyperoxia and hypoxia-related injury needs further refinement and may not be generalizable to all gestations and birth conditions.

Summary

This article reviews the current evidence on oxygen use during delayed cord clamping, during resuscitation of term and preterm neonates, during chest compressions, after return of spontaneous circulation and in the post-resuscitation phase, and the impact of hyperoxia.

Key Messages

Supplemental oxygen during neonatal resuscitation is actively being investigated by researchers worldwide to fill the knowledge gap to avoid hypoxia and hyperoxia while improving neonatal outcomes. Until further evidence emerges, we recommend starting resuscitation in the delivery room of very-low-birth-weight infants with an FiO₂ of 0.3–1, probably in the lower part of this scale, and titrating up by 10–20% every 30 s to achieve the target SpO₂ for age. An SpO₂ of 80–85% should be targeted by 5 min after birth.

Introduction

Oxygen (O₂) is the most frequently used drug in newborns during resuscitation in the delivery room. The delivery of oxygen and response to oxygen are dependent on source, interface and infant’s pathophysiology (shown in online suppl. S1; for all online suppl. material, see https://doi.org/10.1159/000549372). The interfaces for administering oxygen (nasal cannula, prongs, supraglottic airway, tracheal tube, etc.), the concentration (FiO₂) and amount (flow in L/min, delivered pressure in cm H₂O or tidal volume) or device (T-piece resuscitator, ventilator, etc.), can vary based on the infant’s gestation, disease process, and response to resuscitation and ventilation (shown in online suppl. S1) [1]. The deficiency of antioxidant defenses, lung pathology (poor compliance in respiratory distress syndrome; high pulmonary vascular resistance [PVR] in asphyxia and meconium aspiration syndrome; or pulmonary vasoconstriction induced by therapeutic hypothermia [TH]) may influence oxygen requirement. Some of the recommendations for O₂ supplementation are based on clinical trials, some on translational large-model studies and some on expert recommendation. The International Liaison Committee on Resuscitation (ILCOR) advocates to increase inspired O₂ to 100% when chest compressions (CCs) are needed for severe bradycardia or cardiac arrest, to minimize ongoing hypoxic injury in the absence of human trials balancing the caveat to prevent subsequent hyperoxic injury that is demonstrated in animal studies [2]. In preterm infants born at <32 weeks of gestational age (GA), achieving a preductal SpO₂ of >80% and a heart rate of >100 bpm by 5 min after birth are associated with improved outcomes, and prolonged bradycardia with a heart rate of <100 bpm for ≥2 min and SpO₂ of <80% is associated with increased risk of mortality [3] (shown in Fig. 1). Various factors associated with low SpO₂ at 5 min can predispose to higher morbidity and mortality as outlined in Figure 1.

Fig. 1.

Causes of hypoxia in the delivery room. Iatrogenic or correctable factors and infant factors. These include correctable or iatrogenic factors (shown in blue boxes) such as source issues (inadequate FiO₂, flow, pressure, or tidal volume), interface issues (mask leak, improper placement), targeting lower SpO₂ targets in the first few minutes after birth or umbilical cord management (early cord clamping). Neonatal factors include upper airway factors (e.g., glottic closure), lung disease (e.g., respiratory distress syndrome [RDS]), increase in PVR or decrease in pulmonary blood flow/Qp, right to left shunt across the ductus arteriosus, thickened airspace-capillary interface, cardiac dysfunction, and extreme prematurity. These factors can be reversed by administering higher FiO₂, improving the interface (reducing mask leak, early intubation, or supraglottic airway use), deferred cord clamping and targeting higher SpO₂ in the first few minutes after birth (being evaluated by the Optistart trial). Copyright Satyan Lakshminrusimha.

Clinical trials are ongoing to investigate whether the use of higher FiO₂ or a different interface or targeting higher SpO₂ and administering higher FiO₂ during deferred cord clamping (DCC) will confer an advantage and improve outcomes. This review focuses on oxygen use during resuscitation in preterm infants including during DCC, and on term infants requiring CC and the immediate post-resuscitation phase, incorporating recent evidence weighing the risks and benefits of oxygen use.

Oxygen Use during DCC

Umbilical cord management influences neonatal oxygenation. Following immediate cord clamping, the newly born infant is exclusively dependent on the establishment of lungs as the site of gas exchange and gradual increase in oxygen content of the pulmonary venous return (increasing slowly from fetal values of 50–55% SO₂ to 95–100% postnatal levels, shown in online suppl. S2). One approach to improve oxygenation in an extremely preterm newborn born at ≤28 weeks of GA is to provide higher levels of FiO₂ during DCC. Ventilation with high levels of FiO₂ during DCC promotes optimal alveolar oxygenation by both enabling pulmonary vasodilation and enhancing systemic oxygenation via increases in umbilical venous return to the left ventricle. In addition, the PaO₂ in the blood exiting the lung is “diluted” by umbilical venous return, further limiting O₂ toxicity to the infant. Indeed, clinical studies have not shown harm from transient high levels of FiO₂ but have suggested that a lower initial FiO₂ poses an increased risk due to the detrimental effects of hypoxemia. For example, hypoxemia (pulse oximetry-based SpO₂ <80%) at 5 min after birth is associated with a higher risk of severe intraventricular hemorrhage (IVH) and mortality [3]. Furthermore, in a recent trial of neonates who were born at <30 weeks of gestation, initial stabilization (albeit after cord clamping) with 100% O₂ led to less apnea at birth, a greater minute ventilation, higher tidal volumes, improved oxygenation, and a shorter duration of ventilation compared to 30% O₂ without any differences in long-term outcomes [4]. One large network meta-analysis reported that starting resuscitation with high (≥0.90), rather than low (≤0.30), levels of FiO₂ immediately after birth may be associated with reduced mortality in preterm infants born at <32 weeks of GA (low certainty) [5].

Recently updated recommendations from the ILCOR include starting with ≥30% O₂ for resuscitation of preterm infants born at <32 weeks of gestation (weak recommendation, low-certainty of evidence) [6]. These data are based on a recent meta-analysis demonstrating that starting with very high oxygen (90–100%) concentration reduced in-hospital mortality in preterm infants born at <32 weeks of GA[5]. However, none of these trials included infants who received DCC or studies that conducted intact cord resuscitation. Three large multicenter trials that evaluated the use of intact cord resuscitation with low O₂ concentrations during DCC (30%) did not show any differences in their primary outcome [7–9]. Katheria et al. [10] recently conducted a double-blind randomized controlled pilot study (N = 140) comparing 30% versus 100% during DCC. The authors demonstrated that exposure to 100% oxygen during 90 s of DCC reduced hypoxia in the delivery room (adjusted odds ratio, 3.74 [95% CI: 1.8–7.8]) [10]. Grade 2 or 3 BPD was lower in infants who received transiently high levels of O₂, and retinopathy of prematurity requiring surgery and death were not different between groups, reassuring that high levels of inspired O₂ for a short period may not be harmful. These data demonstrate the potential value of high O₂ during DCC and are consistent with other studies that have shown that transient administration of 100% O₂ is not associated with morbidity and may be beneficial. A large multicenter trial (N = 1,000) is being planned by Katheria et al. [10] to demonstrate whether an approach to high O₂ during DCC improves survival without morbidities. Further studies are warranted to establish the safety of using 100% oxygen during DCC.

Oxygen Supplementation during Resuscitation of Preterm Infants

Birth triggers a rapid switch from placental to pulmonary gas exchange. At birth, for optimal pulmonary transition, the newborn develops stable, continuous breathing with an open larynx; lung fluid clears; lung aeration occurs; pulmonary blood flow increases; and pulmonary vascular resistance drops. Preterm infants born at <32 weeks of GA frequently experience suboptimal pulmonary transition, likely due to immature lung architecture and surfactant deficiency. It is debated whether oxygen may play a role in triggering spontaneous breathing and changes in pulmonary blood flow at birth, thus helping extremely preterm infants born at ≤28 weeks of GA with pulmonary transition [4]. Either end of the O₂ spectrum is hazardous: hypoxia worsens pulmonary vasoconstriction, bradycardia, and end-organ ischemia, whereas hyperoxia overwhelms antioxidant capacity, driving oxidative DNA damage that has been linked to bronchopulmonary dysplasia, retinopathy of prematurity, and impaired neurodevelopment [11]. Clinicians, therefore, need a strategy that delivers enough O₂ to allow successful pulmonary transition and meet tissue demands but not so much that it fuels oxidative stress.

Since 2010, international guidelines advised 21–30% O₂ at birth for infants born at <35 weeks GA, with subsequent titration to SpO₂ targets. A 2024 individual-participant-data network meta-analysis of 1,055 infants (NETMOTION) born at <32 weeks of GA from 12 randomized controlled trials found lower in-hospital mortality when resuscitation started with ≥90% O₂ versus ≤30% or 50–65% (odds ratios of 0.45 and 0.34, respectively; low to very low certainty) (shown in online suppl. S3) [5]. These findings drove the 2025 ILCOR recommendation that “it is reasonable to begin at ≥30% O₂,” for infants born at <32 weeks, widening the permissible range up to 100% [6]. The heterogeneity across trials (gestational-age mix, delayed cord clamping, ventilation interfaces, and FiO₂ titration guidelines) means that one size clearly does not fit all. A pragmatic bedside compromise is to start at 30% O₂ for most preterm infants born at <32 weeks, reserving higher starting inspired O₂ concentrations for the more immature (<28 weeks), acidemic, or obviously apneic infants, while committing to prompt titration once heart rate and saturations are known. Ongoing trials will inform how high we should start the FiO₂ in extremely premature infants born at <32 weeks of GA who may need the most help but also are the most vulnerable to prolonged high FiO₂ exposure at birth [12, 13].

Before birth, fetal arterial SaO₂ hovers around 60%. Once breathing begins, saturation climbs steadily toward levels above 90%, yet even vigorous term infants often need 5–10 min or more to get there. As both hypoxia and hyperoxia can be harmful, current practice aims for a trajectory that mirrors the natural course seen in healthy term newborns. Placing a pre-ductal pulse oximeter probe (right hand or wrist) is recommended as soon as positive pressure ventilation begins. Once a stable reading is obtained, it should be compared with the target SpO₂ ranges and the blender is adjusted accordingly. While no single titration algorithm is proven superior, many teams change the inspired O₂ by 20–30% every 30 s until the desired saturation is achieved.

Observational studies show delays of >60 s before the intended FiO₂is actually delivered, and infants spend only ∼30% of the first 10 min within target SpO₂ ranges. For preterm infants born at <32 weeks of gestation, emerging data indicate they should reach about 80–85% by 5 min of life, as infants who do not achieve this target have higher incidence of IVH and mortality [3]. Unfortunately, only 54% of preterm infants born at <32 weeks of GA reach this target with the current oxygenation strategy. Reaching this benchmark may require starting with a higher FiO₂, titrating more aggressively or targeting higher goal SpO₂ for the first few minutes of life. OptiSTART (NCT05849077), an ongoing multicenter trial, compares two different goal SpO₂ ranges and titration strategies in preterm infants born at <31 weeks of GA. Additionally, closed-loop systems may help. In a 2022 feasibility study, an algorithm-controlled blender kept SpO₂ in the Dawson 25–75th centile range equivalent to the manual control, reduced time above SpO₂ target while receiving oxygen, and delivered 40–60 FiO₂ adjustments per infant with no clinician input [14]. Paucity of skilled bedside staff in low-resource settings in low-to-middle income countries makes it a priority to adapt artificial intelligence-based automation of oxygen titration a priority to provide individualized care in low-to-middle income countries where the majority of preterm deliveries occur. Larger trials and regulatory pathways are awaited, but automation could eventually make high-frequency titration routine. Our recommendations for initial oxygenation during resuscitation are shown in Figure 2.

Fig. 2.

Inspired oxygen at initiation of resuscitation in newborns. The current guidelines from the ILCOR are to start ventilation using 30–100% oxygen in preterm infants born at <32 weeks. The Textbook of Neonatal Resuscitation recommends 21–30% for <35 weeks, and 21% oxygen for ≥35 weeks of GA at initiation of ventilation at birth. Copyright Satyan Lakshminrusimha.

Hyperoxia and Oxygen Toxicity

The main goal of O₂ therapy newborns in the delivery room experiencing birth asphyxia is to provide sufficient O₂ to the tissues to avoid anaerobic metabolism. While prevention of hypoxic pulmonary vasoconstriction is essential, it is important to minimize adverse effects of O₂ as well. Although O₂ is essential for life, it is potentially toxic and even mutagenic, induced by oxidative stress and oxygen free radical production (shown in Fig. 3). There are multiple effects of free radicals, and at a cellular level some of them activate transcription factors such as nuclear factor kappa B, activator protein-1, hypoxia inducible factor-1, Nuclear factor E2-related factor 2, as well as inducing apoptosis and necrosis, and others [15]. Cell proliferation and direct damage of lipids, proteins, and DNA [15], along with inhibition of platelet aggregation, may also occur. Term babies have a more developed antioxidant defense than preterm infants, including defenses in umbilical cord blood erythrocytes.

Fig. 3.

Factors contributing to oxidative stress in the newborn. Maternal factors that contribute to fetal inflammation include maternal obesity, smoking, preeclampsia, and chorioamnionitis. Fetal inflammation is associated with oxidative stress. Oxidative stress is associated with impaired mitochondrial biogenesis, decreased activity of superoxide dismutase (SOD) and catalase, reduction in adenosine triphosphate (ATP), and increase in reactive oxygen species (ROS), and down- and up-regulation of genes. In infants with bronchopulmonary dysplasia with pulmonary hypertension (BPD-PH), there is vascular remodeling and pulmonary artery smooth muscle cell proliferation that contribute to increase in PVR, along with pulmonary vascular hypoplasia. ROCK, Rho-kinase, NO, nitric oxide, eNOS, endothelial nitric oxide synthase, cGMP, cyclic guanosine monophosphate. VEGF, vascular endothelial growth factor, HIF-1α, hypoxia inducible factor-1α, HRE, hypoxia response element, PHD, prolyl hydroxylase domain genes. Copyright Satyan Lakshminrusimha.

When assessing oxidative stress in the newly born infant, maternal factors should be kept in mind. A high maternal body mass index, preeclampsia, diabetes, maternal smoking as well as pollutants, may contribute to oxidative stress in the newborn. Inflammation and oxidative stress are two sides of the same coin. Chorioamnionitis, diabetes, and infections in the mother may add to the burden of neonatal oxidative stress. An extremely high PaO₂ is obtained within minutes if asphyxiated term newborns with healthy lungs are ventilated with 100% O₂ in the delivery room [16]. Animal experiments indicate that PaO₂ as high as 40–50 kPa is reached within minutes when 100% O₂ is given [17]. By contrast, ventilation with air normalizes PaO₂ within minutes [17].

During asphyxia, the purine metabolite hypoxanthine accumulates in the tissues and body fluids. During resuscitation/ventilation, hypoxanthine increases rapidly [18]. This observation was important for the understanding that led to the new resuscitation guidelines where 100% O₂ was replaced by air. When hypoxanthine is oxidized to uric acid via xanthine in the presence of xanthine oxidase, superoxide radicals are generated. The combination of high hypoxanthine concentration and high PaO₂ might be detrimental [19]. A linear increase in PaO₂ with FiO₂ was demonstrated in asphyxiated newborn term piglets. A similar pattern was found for hydroxyl radical formation as well as DNA damage [20]. Brain-derived neurotrophic factor, a neuroprotective endogenous compound, decreased with increasing FiO₂ [21]. In a newborn mice model, hyperoxic resuscitation induced inflammation in the brain and lung, the mammalian target of rapamycin pathway was upregulated, and genes for oxidative phosphorylation in all five complexes were inhibited [22]. Hyperoxic resuscitation, therefore, induces inflammation and probably decreases ATP production that may possibly explain increased mortality in term and near-term infants resuscitated with 100% O₂ instead of air.

Vento et al. [23] showed that resuscitation of term babies with pure oxygen induced both kidney and myocardial damage. Additionally, there was an association between hyperoxia in the delivery room and childhood malignancies, especially leukemia [24]. In 2010, ILCOR recommended to start resuscitation of term newborns in the delivery room with air instead of 100% O₂. For preterm infants born at <37 weeks of GA, ILCOR suggested that air and O₂ should be blended and given judiciously.

The initial studies on resuscitation of preterm infants born at <29 weeks of GA were carried out by Wang et al. [25] and Vento et al. [26]. Wang et al. [25] found that air, compared to 100% O₂, was not sufficient for these infants. However, Vento et al. [26] demonstrated an advantage of 30% versus 90% O₂ as the latter was associated with increased oxidative stress and inflammation for days, perhaps weeks after birth in preterm infants born between 24 and 28 weeks of GA. By contrast, Dekker et al. [4] did not find any difference at 24 h in oxidative stress markers in infants born at <30 weeks of GA randomized to ventilation with 100% versus 30% O₂. In a recent study in premature infants born between 28 and 33 weeks of GA, there was no difference in mortality in air versus 100% resuscitated infants, and no difference in hypoxic ischemic encephalopathy (HIE) [27].

Oxidative stress seems to be increased following even a brief hyperoxic resuscitation. This may have long-term effects by injury of several organs, up- and down-regulation of genes, and hyperoxia may also lead to epigenetic changes as well as DNA damage. The optimal initial FiO₂ and how to titrate to achieve an optimal SpO₂ are not known and need further investigation. In future studies, outcome measures should include gene regulation and epigenetic changes.

Oxygen Use during CCs and after Return of Spontaneous Circulation

When a newborn’s heart rate is persistently below 60 bpm despite 30 s of effective ventilation, CCs are indicated and inspired O₂ is increased to 100% (Class of recommendation-2b, level of evidence-consensus from expert opinion based on clinical experience). Resuscitation with 21% O₂ may lead to inadequate oxygenation, delayed pulmonary transition, and elevated PVR and may potentially extend the hypoxic ischemic brain injury (shown in online suppl. S4). In contrast, significant arterial hyperoxemia may occur following recovery after 100% O₂ use, CC and contribute to oxidative stress. Most of the evidence on neonatal CC stems from experiments in the perinatal lamb or postnatal piglet models. Animal studies found no differences in time to achieve return of spontaneous circulation (ROSC) with 21% vs. 100% O₂ during CC. However, Solevag et al. [28] reported lower myocardial oxidative stress with the use of 21% O₂ in a piglet model, and Perez-de-Sa et al. [29] reported extremely high brain tissue PO₂ with 100% O₂ use during CC in a perinatal ovine model. A meta-analysis that included data from animal studies that compared the use of 21% or 100% O₂ during CC found no differences in time to achieve ROSC or mortality [2].

Blood flow to essential organs is low during CC, and provision of 100% O₂ may increase cerebral O₂ delivery. However, hyperoxemia after ROSC in the setting of cerebral hyperemia (secondary to high PaCO₂ and pressure-passive circulation influenced by epinephrine-induced hypertension) may add oxidative stress in addition to reperfusion injury to the brain [30]. Furthermore, use of high FiO₂ after ROSC may predispose to pulmonary/alveolar hyperoxia despite systemic hypoxia. In perinatal lambs ventilated with 100% O₂ for 30 min after birth, lung sections showed bright staining for superoxide anions in both airways and pulmonary arteries, and increased pulmonary arterial contractility in response to norepinephrine (reversed by superoxide dismutase and catalase), compared to ventilation with 21% O₂ [31]. Current guidelines recommend titration of supplemental O₂ to achieve SpO₂ targets (weak recommendation, very-low quality of evidence) once the heart rate recovers. In a perinatal lamb model of asphyxial cardiac arrest, gradual weaning down of inspired O₂ from 100% after ROSC resulted in very high PaO₂ and cerebral O₂ delivery compared to more stable, physiological PaO₂ and cerebral O₂ delivery with abrupt weaning of inspired O₂ to 21% [32]. These findings were corroborated by Badurdeen et al. [33], who additionally reported downregulation of genes encoding NADPH enzymes involved in the generation of free radicals, mitochondrial biogenesis, apoptosis, endoplasmic reticulum stress-induced apoptosis, and antioxidant defense with rapid weaning of FiO₂ after ROSC. To summarize, current evidence supports the use of 100% O₂ when CC are needed, followed by rapid weaning of inspired O₂ after recovery of heart rate, followed by titrating up to achieve SpO₂ targets to avoid hyperoxia and preserve mitochondrial function (shown in online suppl. S4; Fig. 4).

Fig. 4.

Overview of oxygen use during deferred cord clamping, initial resuscitation CCs and ROSC and in the post-resuscitation phase in newborn infants. This figure summarizes the evidence and current guidelines on oxygen use during neonatal deferred cord clamping, initiation of resuscitation, chest compressions, after ROSC, and in the post-ROSC phase during therapeutic hypothermia. Copyright Satyan Lakshminrusimha.

Oxygen Use during Post-Resuscitation Period

All infants, irrespective of gestation, who have required extensive resuscitation for asphyxia need admission to the NICU for monitoring. Oxygen titration following admission to the NICU post-asphyxia has important implications for neurological and pulmonary outcomes. Optimal O₂ delivery to tissues, especially the brain, is critical during the post-resuscitation period. Low PaO₂ (<45 mm Hg or SpO₂ of ≤89%) during the post-resuscitation period can potentially be associated with increased PVR through hypoxic pulmonary vasoconstriction [34]. However, the first NICU blood gas with a PaO₂ of >115 mm Hg is associated with a higher incidence of HIE [35]. This leaves a narrow therapeutic range for PaO₂ in the post-resuscitation phase in the NICU (PaO₂ of 50–100 mm Hg or SpO₂ of 90–97% preductal, shown in Fig. 4).

If the infant has moderate to severe HIE, TH is indicated, often with whole body cooling to a core temperature of 33.5°C. Infants with parenchymal lung disease, such as meconium aspiration syndrome or pneumonia, are at higher risk of developing persistent pulmonary hypertension of the newborn (PPHN) during TH [36]. The authors observed that TH with PPHN as an associated diagnosis is more common than congenital diaphragmatic hernia and is the leading indication for neonatal respiratory ECMO in California [37]. Management of an infant with HIE and PPHN during TH requires close attention to arterial blood gases corrected for the baby’s body temperature [38]. The O₂-hemoglobin dissociation curve is shifted to the left during hypothermia [38] and to achieve the PaO₂ goal of 50–100 mm Hg mentioned above, higher preductal SpO₂ (such as 93–98 or 99%) may be necessary. It is also important to closely monitor blood gas PCO₂ values corrected for body temperature and maintain them in the 45–55 mm Hg range to avoid hypocapnia during TH. Hypocarbia (with arterial PaCO₂ of <35 mm Hg during hypothermia) has been associated with poor neurodevelopmental outcome in infants with moderate to severe HIE [39].

Conclusion

Supplemental O₂ during neonatal resuscitation is actively being investigated by researchers worldwide to avoid hypoxia and hyperoxia while improving neonatal outcomes. Reaching the benchmark of 80–85% SpO₂ by 5 min after birth in newborn infants born at <32 weeks of GA has been shown to decrease severe intraventricular hemorrhage and mortality, and starting resuscitation with higher FiO₂ or titrating up faster may help in achieving this goal. A brief exposure to 100% O₂ during DCC in preterm infants born at ≤28 6/7 weeks of GA reduced hypoxia in the delivery room without increasing morbidity and warrants further investigation. Current ILCOR recommendations are to start with ≥30% of oxygen for infants born at ≤32 weeks of GA. Until further evidence emerges, we recommend starting resuscitation in the delivery room of very-low-birth-weight infants with an FiO₂ of 0.3–1, probably in the lower part of this scale, and titrating up by 10–20% every 30 s to achieve the target SpO₂ for age. An SpO₂ of 80–85% should be targeted by 5 min after birth. Closed-loop automated systems incorporating artificial intelligence to adjust FiO₂ to achieve target SpO₂ ranges may optimize and revolutionize neonatal resuscitation. Recent evidence is lacking regarding SpO₂ targets during resuscitation and in the immediate post-resuscitation phase in term infants. While increasing FiO₂ to 1.0 is recommended during advanced neonatal resuscitation, including CC, FiO₂ should be titrated quickly after ROSC to avoid hyperoxic injury in addition to reperfusion injury in the post-ROSC phase. Infants requiring TH in the post-resuscitation period require close monitoring to maintain tight control of PaO₂ and PaCO₂ to prevent worsening of persistent pulmonary hypertension of the newborn. A graphic summary of these recommendations is shown in Figure 4.

Conflict of Interest Statement

Satyan Lakshminrusimha and Ola Saugstad were members of the journal’s Editorial Board at the time of submission.

Funding Sources

This work has been supported by a Research Grant from the American Academy of Pediatrics-Neonatal Resuscitation program (AAP-NRP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and National Institutes of Health HD109443 (D.S.) and HD072929 (S.L.) and ZOLL Foundation Inc. (D.S.). The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. UL1 TR001860 and linked award 5KL2TR001859 (D.S.), and National Heart Lung and Blood Institute (NHLBI) 1K08HL181183-01 (D.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or AAP-NRP. The funder/sponsor did not participate in planning or devising this work.

Author Contributions

D.S., A.C.K., V.K., S.L., and O.D.S. made substantial contributions to conception, design, data acquisition, extraction, and analysis. All authors contributed to the interpretation of data and drafting the manuscript. All authors critically revised and approved the final version for publication.

Funding Statement

This work has been supported by a Research Grant from the American Academy of Pediatrics-Neonatal Resuscitation program (AAP-NRP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and National Institutes of Health HD109443 (D.S.) and HD072929 (S.L.) and ZOLL Foundation Inc. (D.S.). The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. UL1 TR001860 and linked award 5KL2TR001859 (D.S.), and National Heart Lung and Blood Institute (NHLBI) 1K08HL181183-01 (D.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or AAP-NRP. The funder/sponsor did not participate in planning or devising this work.