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ImportanceAnimal and observational human studies report that delivery of excessive tidal volume (VT) at birth is associated with lung and brain injury. Using a respiratory function monitor (RFM) to guide VTdelivery might reduce injury and improve outcomes.ObjectiveTo determine whether use of an RFM in addition to clinical assessment versus clinical assessment alone during mask ventilation in the delivery room reduces in-hospital mortality and morbidity of infants Study selectionRandomised controlled trials (RCTs) comparing RFM in addition to clinical assessment versus clinical assessment alone during mask ventilation in the delivery room of infants born Data analysisRisk of bias was assessed using Covidence Collaboration tool and pooled into a meta-analysis using a random-effects model. The primary outcome was death prior to discharge.Main outcomeDeath before hospital discharge.ResultsThree RCTs enrolling 443 infants were combined in a meta-analysis. The pooled analysis showed no difference in rates of death before discharge with an RFM versus no RFM, relative risk (RR) 95% (CI) 0.98 (0.64 to 1.48). The pooled analysis suggested a significant reduction for brain injury (a combination of intraventricular haemorrhage and periventricular leucomalacia) (RR 0.65 (0.48 to 0.89), p=0.006) and for intraventricular haemorrhage (RR 0.69 (0.50 to 0.96), p=0.03) in infants receiving positive pressure ventilation with an RFM versus no RFM.ConclusionIn infants

BackgroundThe feasibility and benefits of continuous sustained inflations (SIs) during chest compressions (CCs) during delayed cord clamping (physiological-based cord clamping; PBCC) are not known. We aimed to determine whether continuous SIs during CCs would reduce the time to return of spontaneous circulation (ROSC) and improve post-asphyxial blood pressures and flows in asystolic newborn lambs.MethodsFetal sheep were surgically instrumented immediately prior to delivery at ~139 days’ gestation and asphyxia induced until lambs reached asystole. Lambs were randomised to either immediate cord clamping (ICC) or PBCC. Lambs then received a single SI (SIsing; 30 s at 30 cmH2O) followed by intermittent positive pressure ventilation, or continuous SIs (SIcont: 30 s duration with 1 s break). We thus examined 4 groups: ICC +SIsing, ICC +SIcont, PBCC +SIsing, and PBCC +SIcont. Chest compressions and epinephrine administration followed international guidelines. PBCC lambs underwent cord clamping 10 min after ROSC. Physiological and oxygenation variables were measured throughout.ResultsThe time taken to achieve ROSC was not different between groups (mean (SD) 4.3±2.9 min). Mean and diastolic blood pressure was higher during chest compressions in PBCC lambs compared with ICC lambs, but no effect of SIs was observed. SIcontsignificantly reduced pulmonary blood flow, diastolic blood pressure and oxygenation after ROSC compared with SIsing.ConclusionWe found no significant benefit of SIcontover SIsingduring CPR on the time to ROSC or on post-ROSC haemodynamics, but did demonstrate the feasibility of continuous SIs during advanced CPR on an intact umbilical cord. Longer-term studies are recommended before this technique is used routinely in clinical practice.

ObjectiveIntraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth.MethodsNear-term lambs (139 days’ gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 μg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC.ResultsROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC.ConclusionsIntraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.

BackgroundIn neonatal resuscitation, a ventilation device providing positive end-expiratory pressure (PEEP) is recommended. There is limited information about PEEP delivery in vivo, using different models of self-inflating bag (SIB) at different inflation rates and PEEP settings.MethodsWe compared PEEP delivery to intubated preterm lambs using four commonly available models of paired SIBs and PEEP valves, with a T-piece, with gas flow of 8 L/min. Peak inspiratory pressure inflations of 30 cmH2O, combined with set PEEP of 5, 7 and 10 cmH2O, were delivered at rates of 20, 40 and 60/min. These combinations were repeated without gas flow. We measured mean PEEP, maximum and minimum PEEP, and its difference (PEEP reduction).ResultsA total of 3288 inflations were analysed. The mean PEEP delivered by all SIBs was lower than set PEEP (P2O. In 55% of combinations, the presence of gas flow resulted in increased PEEP delivery (range difference 0.3–2 cmH2O). The mean PEEP was closer to set PEEP with faster inflation rates and higher set PEEPs. The mean (SD) PEEP reduction was 3.9 (1.6), 8.2 (1.8), 2 (0.6) and 1.1 (0.6) cmH2O with the four SIBs, whereas it was 0.5 (0.2) cmH2O with the T-piece.ConclusionsPEEP delivery with SIBs depends on the set PEEP, inflation rate, device model and gas flow. At recommended inflation rates of 60/min, some devices can deliver PEEP close to the set level, although the reduction in PEEP makes some SIBs potentially less effective for lung recruitment than a T-piece.

Background and objectivesDelivery of inadvertent high tidal volume (VT) during positive pressure ventilation (PPV) in the delivery room is common. High VT delivery during PPV has been associated with haemodynamic brain injury in animal models. We examined if VT delivery during PPV at birth is associated with brain injury in preterm infants MethodsA flow-sensor was placed between the mask and the ventilation device. VT values were compared with recently described reference ranges for VT in spontaneously breathing preterm infants at birth. Infants were divided into two groups: VTT>6 mL/kg (normal and high VT, respectively). Brain injury (eg, intraventricular haemorrhage (IVH)) was assessed using routine ultrasound imaging within the first days after birth.ResultsA total of 165 preterm infants were included, 124 (75%) had high VT and 41 (25%) normal VT. The mean (SD) gestational age and birth weight in high and normal VT group was similar, 26 (2) and 26 (1) weeks, 858 (251) g and 915 (250) g, respectively. IVH in the high VT group was diagnosed in 63 (51%) infants compared with 5 (13%) infants in the normal VT group (P=0.008).Severe IVH (grade III or IV) developed in 33/124 (27%) infants in the high VT group and 2/41 (6%) in the normal VT group (P=0.01).ConclusionsHigh VT delivery during mask PPV at birth was associated with brain injury. Strategies to limit VT delivery during mask PPV should be used to prevent high VT delivery.

ObjectiveUmbilical cord milking (UCM) at birth may benefit preterm infants, but the physiological effects of UCM are unknown. We compared the physiological effects of two UCM strategies with immediate umbilical cord clamping (UCC) and physiological-based cord clamping (PBCC) in preterm lambs.MethodsAt 126 days’ gestational age, fetal lambs were exteriorised, intubated and instrumented to measure umbilical, pulmonary and cerebral blood flows and arterial pressures. Lambs received either (1) UCM without placental refill (UCMwoPR); (2) UCM with placental refill (UCMwPR); (3) PBCC, whereby ventilation commenced prior to UCC; or (4) immediate UCC. UCM involved eight milks along a 10 cm length of cord, followed by UCC.ResultsA net volume of blood was transferred into the lamb during UCMwPR (8.8 mL/kg, IQR 8–10, P=0.01) but not during UCMwoPR (0 mL/kg, IQR −2.8 to 1.7) or PBCC (1.1 mL/kg, IQR −1.3 to 4.3). UCM had no effect on pulmonary blood flow, but caused large fluctuations in mean carotid artery pressures (MBP) and blood flows (CABF). In UCMwoPR and UCMwPR lambs, MBP increased by 12%±1% and 8%±1% and CABF increased by 32%±2% and 15%±2%, respectively, with each milk. Cerebral oxygenation decreased the least in PBCC lambs (17%, IQR 13–26) compared with UCMwoPR (26%, IQR 23–25, P=0.03), UCMwPR (35%, IQR 27–44, P=0.02) and immediate UCC (34%, IQR 28–41, P=0.02) lambs.ConclusionsUCMwoPR failed to provide placental transfusion, and UCM strategies caused considerable haemodynamic disturbance. UCM does not provide the same physiological benefits of PBCC. Further review of UCM is warranted before adoption into routine clinical practice.

ObjectiveLung ultrasound (LUS) has shown promise as a diagnostic tool for the evaluation of the newborn with respiratory distress. No study has described LUS during ‘normal’ transition. Our goal was to characterise the appearance of serial LUS in healthy newborns from the first minutes after birth until airway liquid clearance is achieved.Study designProspective observational study.SettingSingle-centre tertiary perinatal centre in Australia.PatientsOf 115 infants born at ≥35 weeks gestational age, mean (SD) gestational age of 386/7 weeks±11 days, mean birth weight of 3380±555 g, 51 were delivered vaginally, 14 via caesarean section (CS) after labour and 50 infants via elective CS.InterventionsWe obtained serial LUS videos via the right and left axillae at 1–10 min, 11–20 min and 1, 2, 4 and 24 hours after birth.Main outcome measuresLUS videos were graded for aeration and liquid clearance according to a previously validated system.ResultsWe analysed 1168 LUS video recordings. As assessed by LUS, lung aeration and airway liquid clearance occurred quickly. All infants had an established pleural line at the first examination (median=2 (1–4) min). Only 14% of infants had substantial liquid retention at 10 min after birth. 49%, 78% and 100% of infants had completed airway liquid clearance at 2, 4 and 24 hours, respectively.ConclusionsIn healthy transitioning newborn infants, lung aeration and partial liquid clearance are achieved on the first minutes after birth with complete liquid clearance typically achieved within the first 4 hours of birth.Trial registration numberANZCT 12615000380594.

Objective While delayed umbilical cord clamping (UCC) is thought to facilitate placental to infant blood transfusion, the physiological factors regulating flow in the umbilical arteries and veins during delayed UCC is unknown. We investigated the effects of gravity, by changing fetal height relative to the placenta, and ventilation on umbilical blood flows and the cardiovascular transition during delayed UCC at birth. Methods Catheters and flow probes were implanted into preterm lambs (128 days) prior to delivery to measure pulmonary, carotid, umbilical artery (UaBF) and umbilical venous (UvBF) blood flows. Lambs were placed either 10 cm below or 10 cm above the ewe. Ventilation commenced 2–3 min before UCC and continued for 30 min after UCC. Results Gravity reduced umbilical and cerebral flows when lambs were placed below the midline, but the reduction in UaBF and UvBF was similar. Ventilation during delayed UCC reduced UvBF and UaBF by similar amounts, irrespective of the lamb9s position, such that flows into and out of the placenta remained balanced. The effects of ventilation on umbilical flows were much greater than the effects of gravity, but no net placental to lamb blood transfusion could be detected under any condition. Cardiovascular parameters, cerebral oxygen kinetics and final blood volumes were similar in both groups 5 min after UCC. Conclusions Gravity caused small transient effects on umbilical and cerebral flow, but given changes were similar in umbilical arteries and veins, no net placental transfusion was detected. Ventilation during delayed UCC has a markedly greater influence on cardiovascular function in the newborn.

Objective At birth, an initial sustained inflation (SI) uniformly aerates the lungs, increases arterial oxygenation and rapidly improves circulatory recovery in asphyxiated newborns. We hypothesised that lung aeration, in the absence of an increase in arterial oxygenation, can increase heart rate (HR) in asphyxiated near-term lambs. Interventions Lambs were delivered and instrumented at 139±2 days of gestation. Asphyxia was induced by umbilical cord clamping and then delaying the onset of ventilation until mean carotid arterial pressures (CAPs) had decreased 2 ; n=6), 5% oxygen (O 2 ; n=6), 21% O 2 (n=6) or 100% O 2 (n=6) followed by ventilation in air for 30 min. Main outcome measures HR, CAP and pulmonary blood flow (PBF) were continuously recorded. Results HR and PBF increased more quickly in lambs resuscitated with 100% and 21% O 2 than with 5% O 2 or N 2 . HR and PBF recovery in the 5% O 2 group was delayed relative to all other oxygen SI groups. HR in 5%, 21% and 100% O 2 groups reached 100 bpm before the SI was complete. HR and PBF in the N 2 group did not increase until 10 s after the SI was completed and ventilation was initiated with air. CAP tended to increase quicker in all O 2 groups than in N 2 group. Conclusions Oxygen content during an SI is important for circulatory recovery in asphyxiated lambs. This increase in HR is likely driven by the increase in PBF and venous return to the heart.