Chest compression (CC) is an infrequent event (0.08%) in newborns delivered at near-term and term gestation, and happens at higher frequency (~10%) in preterm deliveries (1–5). In addition, outcome studies of deliveries requiring resuscitation or CC have reported high rates of mortality and neurodevelopmental impairment in surviving children (1–5). The poor prognosis associated with resuscitation requiring CC alone and/or medications in the delivery room (DR) raises questions as to whether improved cardiopulmonary resuscitation (CPR) techniques specifically tailored toward the newborn infant could improve outcomes.

Asphyxia, a condition of impaired gas exchange with simultaneous hypoxia and hypercapnia leading to a mixed metabolic and respiratory acidosis, is the most common reason that newborns fail to make successful transition (6, 7). Asphyxia could result from either failure of placental gas exchange before delivery (e.g., abruption and chorioamnionitis) or deficient pulmonary gas exchange immediately after birth (e.g., apnea, airway obstruction, and respiratory distress syndrome) (6, 7). Asphyxia depresses myocardial function leading to cardiogenic shock, pulmonary hypertension, mesenteric reperfusion, and acute renal failure. Newborn infants present with serve bradycardic or asystole at birth as a consequence of asphyxia. Current resuscitation guidelines recommend to initiate CC if heart rate remains <60/min despite adequate ventilation with supplementary oxygen for 30 s; CC should be then performed at a rate of 90/min with 30 ventilations 3:1 C:V (Figure 1A) (8) to achieve adequate oxygen delivery (9–11).

Neonatal bradycardia or cardiac arrest is caused by hypoxia rather than primary cardiac compromise; therefore, providing ventilation is more beneficial (9–11). However, the optimal C:V ratio that should be used during neonatal resuscitation to optimize coronary and cerebral perfusion while providing adequate ventilation of an asphyxiated newborn remains unknown.

Animal studies on cardiac arrest induced by asphyxia in newborn piglets demonstrated that combining CC with ventilations improves ROSC and neurological outcome at 24 h compared to ventilations or CC alone (12–14). Solevåg et al. performed a study investigating alternating nine CC and three ventilations in asphyxiated piglets with cardiac arrest with the hypothesis that nine CC would generate higher diastolic blood pressure (15). The time to ROSC was similar between the two approaches (150 and 148 s for 3:1 and 9:3 C:V, respectively). Similarly, C:V ratios of 3:1 and 15:2 were compared using the same model (16). Although the 15:2 C:V ratio provided higher mean CC per minute (75 versus 58 for 3:1), time to ROSC was similar between groups (median time of 195 and 150 s for 15:2 and 3:1, respectively) (16). These studies suggest that during neonatal CPR, higher C:V ratios do not improve outcomes, and potentially a higher ventilation rate is needed.

This is further supported by manikin studies showing higher ventilation rates during simulated CPR using 3:1 C:V compared with higher C:V ratios (17–19). A more recent neonatal manikin study examined respiratory parameters during neonatal CPR and reported that a 3:1 C:V ratio delivered significantly higher minute ventilation of 191 mL/kg compared to the minute ventilation at 9:3 and 15:2 C:V ratios (140 and 77 mL/kg/min, respectively) (20). A further manikin study compared 3:1 C:V with continuous CC with asynchronous ventilations (CCaV) using 90 CC and 30 non-synchronized inflations and reported significantly higher minute ventilation in the CCaV group compared to the 3:1 group (221 versus 191 mL/kg/min, respectively) (21). Schmölzer et al. compared 3:1 C:V CPR with CCaV in a piglet model of neonatal asphyxia and reported similar minute ventilation (387 versus 275 mL/kg) (22). There was also a similar time to ROSC (143 and 114 s for 3:1 and CCaV, respectively) and survival (3/8 and 6/8, respectively). The same manikin (21) and animal study (22) also reported similar tidal volume (V_T) delivery between 3:1 C:V and CCaV [manikin study V_T 6.4 and 5.6 mL/kg (21), respectively and animal study V_T 14.7 versus 11.0 mL/kg (22)]. In a secondary analysis of the study by Schmölzer et al. (22), Li et al. reported that during 3:1 C:V a cumulated loss of V_T of 4.5 mL/kg occurs for each 3:1 C:V cycle (Figure 2A) (23). Similarly, during CCaV, a cumulated loss of V_T of 9.1 mL/kg for each cycle of three CC and one inflation were observed (23). This suggests a potential loss in V_T during CC, which could cause lung derecruitment, hence hamper oxygenation and therefore ROSC. A recent pilot randomized trial in the DR reported that the exhaled CO₂ was significantly higher in the CC + sustained inflation (SI) group with 11 (9) mmHg compared to 2 (1) mmHg (p < 0.001) in the 3:1 C:V ratio group during CPR suggesting improved gas exchange in the CC + SI group (24). Further, an argument of synchronized CPR is the potential interference of non-synchronized CC with V_T delivery, resulting in impairment of oxygen delivery. However, the study by Schmölzer et al. observed that 29 and 25% of manual inflations were similarly affected during CC using CCaV or 3:1 C:V CPR (22), respectively. These studies suggest that no advantages (e.g., oxygen delivery and V_T or minute ventilation) of using CCaV compared to 3:1 C:V.

Reoxgenation and adequate blood flow are the cornerstones of neonatal CPR. Any effective resuscitative maneuver should increase blood flow and optimize oxygen delivery. In addition to standard CPR, maneuvers that raise intrathoracic pressure can significantly increase carotid blood flow during CPR. Chandra et al. provided ventilation at a high airway pressure while simultaneously performing CC in an animal model and demonstrated increased carotid flow without compromising oxygenation (25). Further, studies in preterm lambs have demonstrated that an SI also increases intrathoracic pressure without impeding blood flow (26). In the resuscitation of asphyxiated newborn piglets, Schmölzer et al. recently reported that passive ventilation during CC, achieved by superimposing CC with an SI (CC + SI) (Figure 1B) (8), significantly improved hemodynamics, minute ventilation, and time to ROSC compared to the current approach of using a 3:1 C:V ratio (mean arterial pressure: 51 versus 31 mmHg; pulmonary arterial pressure: 41 versus 31 mmHg; mean minute ventilation: 936 versus 623 mL/kg; and median time to ROSC: 38 versus 143 s, respectively) (8). However, the study by Schmölzer et al. used a CC rate of 120/min (in the CC + SI group), which is higher than the currently recommended CC rate of 90/min, which could have also added to the improved outcomes. A recent study using a perinatal cardiac arrest lamb model with transitioning fetal circulation and fluid filled lungs reported that CC + SI is as effective as 3:1 C:V ratio in achieving ROSC (27).

Improved left ventricular ejection fraction have been postulated after review of computer tomography images of neonates when CC with a 1/3 anterior–posterior chest diameter was compared with a 1/4 anterior–posterior chest diameter (49). The current neonatal resuscitation guidelines recommend a 1/3 anterior–posterior chest diameter during CPR (9–11). Adequate CC depth is important to optimize cardiac output. However, compressing to deep could cause rib fractures, cardiac contusion, and other thoracic injuries (7). While compressing to shallow might not create the required cardiac output or diastolic blood pressure (50, 51). A retrospective review of six infants (2 weeks to 7.3 months old) with indwelling arterial blood pressure monitoring reported that CC with a 1/2 anterior–posterior chest diameter produced significantly higher systolic blood pressure but similar diastolic blood pressure compared with CC using a 1/3 anterior–posterior chest diameter. However, the optimal CC depth has not been rigorously evaluated in neonates. Furthermore, no study has examined tidal volume delivery with different anterior–posterior chest diameter.

Successful resuscitation from cardiac arrest or severe bradycardia requires the delivery of high-quality CC while providing adequate ventilation. However, until now, no study has examined different CC techniques during neonatal resuscitation in asphyxiated newborn infants, and randomized controlled trials are urgently needed.

Concept, literature search, review of the data, writing of the manuscript, and review of the manuscript: NB, MO, CF, SO, P-YC, and GS.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.