Key points• Delayed cord clamping improves circulatory stability in preterm infants at birth, but the underlying reason is not known.• In a new preterm lamb study we investigated whether delayed cord clamping until ventilation had been initiated improved pulmonary, cardiovascular and cerebral haemodynamic stability.• We demonstrated that ventilation prior to cord clamping markedly improves cardiovascular function by increasing pulmonary blood flow before the cord is clamped, thus further stabilising the cerebral haemodynamic transition.• These results show that delaying cord clamping until after ventilation onset leads to a smoother transition to newborn life, and probably underlies previously demonstrated benefits of delayed cord clamping.Abstract Delayed cord clamping improves circulatory stability in preterm infants at birth, but the underlying physiology is unclear. We investigated the effects of umbilical cord clamping, before and after ventilation onset, on cardiovascular function at birth. Prenatal surgery was performed on lambs (123 days) to implant catheters into the pulmonary and carotid arteries and probes to measure pulmonary (PBF), carotid (CaBF) and ductus arteriosus blood flows. Lambs were delivered at 126 ± 1 days and: (1) the umbilical cord was clamped at delivery and ventilation was delayed for about 2 min (Clamp 1st; n = 6), and (2) umbilical cord clamping was delayed for 3-4 min, until after ventilation was established (Vent 1st; n = 6). All lambs were subsequently ventilated for 30 min. In Clamp 1st lambs, cord clamping rapidly (within four heartbeats), but transiently, increased pulmonary and carotid arterial pressures (by ∼30%) and CaBF (from 30.2 ± 5.6 to 40.1 ± 4.6 ml min −1 kg −1 ), which then decreased again within 30-60 s. Following ventilation onset, these parameters rapidly increased again. In Clamp 1st lambs, cord clamping reduced heart rate (by ∼40%) and right ventricular output (RVO; from 114.6 ± 14.4 to 38.8 ± 9.7 ml min −1 kg −1 ), which were restored by ventilation. In Vent 1st lambs, cord clamping reduced RVO from 153.5 ± 3.8 to 119.2 ± 10.6 ml min −1 kg −1 , did not affect heart rates and resulted in stable blood flows and pressures during transition. Delaying cord clamping for 3-4 min until after ventilation is established improves cardiovascular function by increasing pulmonary blood flow before the cord is clamped. As a result, cardiac output remains stable, leading to a smoother cardiovascular transition throughout the early newborn period.

Major cardiovascular changes occur at birth, including increased pulmonary blood flow (PBF) and closure of the ductus arteriosus (DA), which acts as a low resistance shunt between the fetal pulmonary and systemic circulations. Although the pressure gradient between these circulations reverses after birth, little is known about DA blood flow changes and whether reverse DA flow contributes to PBF after birth. Our aim was to describe the changes in PBF and DA flow before, during and after the onset of pulmonary ventilation at birth. Flow probes were implanted on the left pulmonary artery (LPA) and DA in preterm fetal sheep (n = 8) ∼3 days before they were delivered and ventilated. Blood flow was measured in the LPA and DA, before and after umbilical cord occlusion (UCO) and for 2 h after ventilation onset. Following UCO, DA flow decreased from 534 ± 57 ml min −1 to 237 ± 29 ml min −1 which reflected a similar reduction in right ventricular output. Within 5 min of ventilation onset, PBF increased from 11 ± 6 ml min −1 to 230 ± 13 ml min −1 whereas DA flow decreased to −172 ± 54 ml min −1 ; negative values indicate reverse DA flow (left-to-right shunting). Reverse flow through the DA contributed up to 50% of total PBF at 30 min and a decrease in this contribution accounted for 71 ± 13% of the time-related decrease in PBF after birth. DA blood flow is very dynamic after birth and depends upon the pressure gradient between the pulmonary and systemic circulations. Following ventilation, reverse DA flow provided a significant contribution to total PBF after birth.

However, the effect of PEEP on PBF in preterm infants with immature lungs and a patent ductus arteriosus is unknown. Fetal sheep were catheterized at 124 days of gestation (term ϳ147 days), and a flow probe was placed around the left pulmonary artery to measure PBF. At 127 days, lambs were delivered and ventilated from birth with a tidal volume of 5 ml/kg and 4-cmH 2O PEEP; PEEP was changed to 0, 8, and 12 cmH2O in random order, returning to 4 cmH2O between each change. Increasing PEEP from 4 to 8 cmH2O and from 4 to 12 cmH2O decreased PBF by 20.5 and 41.0%, respectively, and caused corresponding changes in PVR; reducing PEEP from 4 to 0 cmH 2O did not affect PBF. Despite decreasing PBF, increasing PEEP from 4 to 8 cmH 2O and 12 cmH2O improved oxygenation of lambs. Increasing and decreasing PEEP from 4 cmH2O significantly changed the contour of the PBF waveform; at a PEEP of 12 cmH2O, end-diastolic flow was reduced by 82.8% and retrograde flow was reestablished. Although increasing PEEP improves oxygenation, it adversely affects PBF and PVR shortly after birth, alters the PBF waveform, and reestablishes retrograde flow during diastole. ventilation; pulmonary blood flow; fetus; preterm birth INFANTS BORN VERY PRETERM (Ͻ28 wk gestation) have surfactant-deficient and immature lungs, with a small surface area and a thick air-blood barrier that impairs gas exchange (16,17). Consequently, very preterm infants usually require resuscitation at birth and assisted ventilation during their first weeks of extrauterine life, although this increases the risk of injuring their lungs. It is important to identify ventilation techniques that maximize oxygenation of very preterm infants without injuring their lungs or adversely affecting the changes in pulmonary physiology that are essential for the transition to air breathing at birth. The application of positive end-expiratory pressure (PEEP) is important for maintaining lung volumes and improving oxygenation in very preterm infants (25) and reduces the risk of lung injury (2). However, little is known of the effects of PEEP on the transition of the lung into a functional gas-exchange organ at birth, particularly the increase in pulmonary blood flow (PBF), which is essential for surviving the transition to extrauterine life.During fetal development, pulmonary vascular resistance (PVR) is high (13, 15), and, as a result, the fetal lungs receive only ϳ12% of right ventricular output; most bypasses the lungs and passes directly into the systemic circulation via the ductus arteriosus (DA) (3,14,28,31,33). The high PVR and the presence of the DA confer unique characteristics to the contour of the PBF waveform in the fetus (31), particularly during diastole when the flow is largely retrograde and exits the pulmonary circulation via the DA (31). However, at birth PVR decreases, and as a result PBF increases (8-to 10-fold) (3,19,31), allowing the pulmonary circulation to accommodate the entire output of the right ventricle; the DA must also close to separate the pulmonary and systemic ...

BackgroundAs measurement of arterial oxygen saturation (SpO2) is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.AimWe investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.MethodsSystemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2) were measured continuously in apnoeic preterm lambs (126±1 day gestation). Positive pressure ventilation was initiated either 1) prior to umbilical cord clamping, or 2) after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.ResultsClamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5–6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.ConclusionThe establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.