Volume expanders are indicated in the delivery room when an asphyxiated neonate is not responding to the steps of neonatal resuscitation and has signs of shock or a history of acute blood loss. Fetal blood loss (e.g., feto-maternal hemorrhage) may contribute to perinatal asphyxia. Cord compression or a tight nuchal cord can selectively occlude a thin-walled umbilical vein, resulting in feto-placental transfusion and neonatal hypovolemia. For severe bradycardia or cardiac arrest secondary to fetal blood loss, Neonatal Resuscitation Program (NRP) recommends intravenous volume expanders (crystalloids such as normal saline or packed red blood cells) infused over 5 to 10 min. Failure to recognize hypovolemia and subsequent delay in volume replacement may result in unsuccessful resuscitation due to lack of adequate cardiac preload. However, excess volume load in the presence of myocardial dysfunction from hypoxic–ischemic injury may precipitate pulmonary edema and intraventricular hemorrhage (especially in preterm infants). Emergent circumstances and ethical concerns preclude the performance of prospective clinical studies evaluating volume replacement during neonatal resuscitation. Translational studies, observational data from registries and clinical trials are needed to investigate and understand the role of volume replacement in the delivery room in term and preterm neonates. This article is a narrative review of the causes and consequences of acute fetal blood loss and available evidence on volume replacement during neonatal resuscitation of asphyxiated neonates.

The combination of perinatal acidemia with postnatal hyperoxia is associated with a higher incidence of hypoxic-ischemic encephalopathy (HIE) in newborn infants. In neonatal cardiac arrest, current International Liaison Committee on Resuscitation (ILCOR) and Neonatal Resuscitation Program (NRP) guidelines recommend increasing inspired O2 to 100% during chest compressions (CC). Following the return of spontaneous circulation (ROSC), gradual weaning from 100% O2 based on pulse oximetry (SpO2) can be associated with hyperoxia and risk for cerebral tissue injury owing to oxidative stress. We hypothesize that compared to gradual weaning from 100% O2 with titration based on preductal SpO2, abrupt or rapid weaning of inspired O2 to 21% after ROSC or use of 21% O2 during CC followed by upward titration of inspired O2 to achieve target SpO2 after ROSC will limit hyperoxia after ROSC. Nineteen lambs were randomized before delivery and asphyxial arrest was induced by umbilical cord occlusion. There was no difference in oxygenation during chest compressions between the three groups. Gradual weaning of inspired O2 from 100% O2 after ROSC resulted in supraphysiological PaO2 and higher cerebral oxygen delivery compared to 21% O2 during CC or 100% O2 during CC followed by abrupt weaning to 21% O2 after ROSC. The use of 21% O2 during CC was associated with very low PaO2 after ROSC and higher brain tissue lactic acid compared to other groups. Our findings support the current recommendations to use 100% O2 during CC and additionally suggest the benefit of abrupt decrease in inspired oxygen to 21% O2 after ROSC. Clinical studies are warranted to investigate optimal oxygen titration after chest compressions and ROSC during neonatal resuscitation.