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

Abstract

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.

Introduction

Intrauterine hypoxia or factors influencing the physiologic changes during transition can make a newborn limp, apneic or bradycardic.1., 2. Many preterm infants experience suboptimal transition, producing bradycardia and/or apnea requiring resuscitation at birth.3., 4. A rising heart rate (HR) is an important indicator of effective ventilation in a bradycardic newborn.5., 6., 7., 8. If the HR remains below 100 bpm after the initial steps, International Liaison Committee on Resuscitation (ILCOR) guidelines recommend positive pressure ventilation.5., 7. If the HR remains below 60 bpm after attempting adequate ventilation, ILCOR guidelines recommend chest compressions.5., 7. Preterm infants who received chest compression in the delivery room (DR-CPR) have increased mortality or morbidity in survivors.9., 10., 11., 12., 13., 14. Fortunately, most preterm infants with bradycardia respond to adequate ventilation and few require DR-CPR.4., 6. It remains unclear if the duration of bradycardia increases morbidity and mortality in preterm infants not requiring DR-CPR.

The largest clinical trial of initial oxygen (O₂) concentration for preterm resuscitation in the DR so far showed a higher incidence of bradycardia in infants whose resuscitation began with room air.¹⁵ It was unclear if the duration of bradycardia differed between preterm infants resuscitated with low vs high O₂ concentration.¹⁵ In a post-hoc analysis, O₂ saturation (SpO₂) < 80% at 5 min after birth was associated with increased mortality.¹⁶ Along with O₂ content of blood, cardiac output is important for adequate O₂ delivery to tissues.¹⁷ Prolonged bradycardia (PB) compromises cardiac output, causing inadequate O₂ delivery and tissue hypoxia. Intermittent bradycardia in preterm neonates during their neonatal intensive care unit (NICU) stay has been associated with decreased cerebral O₂ saturation and motor impairment.18., 19., 20. It is unclear if prolonged bradycardia and low SpO₂ in the DR have an additive significance on adverse outcomes.

We therefore obtained individual patient SpO₂ and HR data from randomized controlled trials (RCT) that compared outcomes of high versus low inspired O₂ resuscitation strategies in infants <32 weeks gestational age (GA). We hypothesized that infants <32 weeks GA who are bradycardic immediately after birth and remain bradycardic for two minutes or more will be at a higher risk of the primary outcome of neonatal mortality and secondary morbidities. We also hypothesized that preterm infants whose resuscitation started with low O₂ concentration (21–30%) had longer bradycardia.