Table 1.

Selected studies about volume expansion in neonates.

References	Type	Design/Objective	Population	Main finding and/or key messages
STUDIES CITED IN GUIDELINES
Kirkman et al. (5)	Human, case series	Descriptive cohort study	Ten nearly term neonates	The authors described different aspects of post-hemorrhagic anemia and shock due to placental causes
Wyckoff et al. (6)	Human, retrospective review	Descriptive cohort study	Resuscitation registry, 13 infants >34 weeks receiving volume expansion between 01/99 and 06/01	Of 37,972 infants, 23 received CPR, including 13 with volume expansion. 10 of 13 received volume expansion for persistent bradycardia despite CPR, and only three of 13 received volume expansion for suspicion of hypovolemia with poor perfusion
Wyckoff et al. (7)	Animal, prospective	RCT: To compare albumin, normal saline, and SHAM on development of pulmonary edema and restoration of mean arterial pressure during resuscitation of asphyxiated piglets	37 Yucatan miniature swine, (weight 2.2 ± 0.7 kg, postnatal age: 8 ± 4 d)	Volume expansion during resuscitation did not improve mean arterial pressure, and acute recovery of mean arterial pressure was poorer with normal saline compared with albumin. Volume expansion was associated with increased pulmonary edema. In the absence of hypovolemia, volume expansion during neonatal resuscitation is not beneficial
Mayock et al. (8)	Animal, prospective	RCT: To study cerebral blood flow (CBF) regulation, possibly associated with changes in cerebral venous pressure after acute volume expansion in normovolemic developing animals	Protocol 1: 8 preterm sheep fetuses (weight 0.78 ± 0.14 kg, age 95 ± 3 d) Protocol 2: 8 preterm sheep fetuses (weight 0.73 ± 0.04 kg, age 95 ± 1 d)	Rapid volume expansion in the normoxic normovolemic preterm fetal sheep causes a dilutional anemia without a compensatory increase in CBF and, consequently, a decrease in fetal cerebral oxygen delivery (OD). Severe fetal hypoxemia induced after volume expansion further compromises cerebral OD
SELECTED STUDIES COMPARING DIFFERENT VOLUME AGENTS
Roger et al. (9)	Animal, prospective	RCT: To compare the rapidity of shock reversal with lactated Ringer (LR) or hydroxyethyl starch (HES) at the early phase of controlled haemorrhagic shock	36 piglets: (weight 20–31 kg)	Restoration of mean arterial pressure (MAP) was four times faster with HES than with LR in the early phase of controlled hemorrhagic shock. Time to restore the baseline MAP value of +10% was significantly lower in the HES group. The initial infused volume was 279 ± 119 ml in the HES group and 1,011 ± 561 ml in the LR group
Mauch et al. (10)	Animal, prospective	RCT: To evaluate the effect of a single fast intravenous crystalloid or colloid fluid bolus on blood coagulation as measured by rotation thromboelastometry.	32 piglets (weight 5.1 ± 0.4 kg, age 2–5 weeks)	After moderate but very fast volume loading, HES, and gelatine impair blood coagulation to a larger extent as compared with albumin or normal saline, while no significant differences were observed between both artificial colloids
So et al. (11)	Human, prospective	RCT: To compare the efficacy of a colloid (5% albumin) and a crystalloid (isotonic saline) solution for treating hypotension in mechanically ventilated preterm infants within the first 2 h of life	63 preterm infants (weight 0.54–1.95 kg, gestational age 23–34 weeks)	There was no difference in the volume of the test solutions required between the two groups. Isotonic saline is as effective as 5% albumin for treating hypotension in preterm infants, and it has the additional advantage of causing less fluid retention in the first 48 h
Oca et al. (12)	Human, prospective	RCT: To assess the comparative efficacy of normal saline (NS) and 5% albumin (ALB) for treatment of hypotension in the acutely ill newborn	41 newborn infants < 24 h old (weight 0.62–4.28 kg gestational age 25–40 weeks)	NS was shown to be as effective as ALB for the correction of acute hypotension in the newborn infant
Lynch et al. (13)	Human, prospective	RCT: To compare responses to bolus infusion of 5% albumin (ALB) or normal saline (NS) for hypotension in neonates	41 newborn infants < 24 h old (ALB: weight 1.617 ± 0.838 kg gestational age 30.8 ± 4.4 weeks) (NS: weight 1.528 ± 0.830 kg gestational age 30.1 ± 4.1 weeks)	In hypotensive neonates, ALB results in a greater likelihood of achieving normotension and decreased subsequent use of vasopressors when compared to NS
Shalish et al. (14)	Human, review	To investigate the use and evidence of albumin during resuscitation and in the neonatal intensive care unit		There is currently no clinical evidence or physiological rationale to favor the use of albumin over crystalloids in the delivery room resuscitation. Furthermore, only the study from Wyckoff MH, et al. (Use of Volume Expansion During Delivery Room Resuscitation in Near-Term and Term Infants.) is referenced to this topic.
Finn et al. (2)	Human, review	To review the available literature and current guidelines to determine which infants will benefit from Volume Resuscitation (VR), the frequency of VR, and the choice of agents used.		In a setting with presumed or obvious blood loss such as placental abruption or fetal-to-maternal transfusion, VR therapy may play indeed an important role. However, for other clinical scenarios such as asphyxia, the current set of clinical and technical tools makes it difficult to differentiate the haemodynamically compromised infant who will benefit from volume therapy from the normovolaemic asphyxiated infant who may, potentially, be further compromised by volume therapy. …fresh whole blood should be used if available.