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.

Fetal lung growth depends on the degree to which lungs are distended with luminal liquid. Fetal lungs are highly distended such that mean luminal volume exceeds the static relaxation volume. This high level of expansion is maintained by fetal breathing movements and by resistive effects of the upper airway during apnea; both factors oppose lung recoil. Mechanical stress in lung and other tissues stimulates cell division and tissue remodeling. Potential transduction mechanisms involve direct effects of cellular tension and mediation of locally released mitogenic factors. Further studies are required to further define links between lung tissue stress, increased growth, structural remodeling, and the endocrine environment. A common cause of fetal lung hypoplasia is a sustained reduction in mean lung expansion. Studies of mechanisms controlling fetal lung expansion have led to insights into the etiology of fetal lung hypoplasia and how it may be remedied in utero. Fetal lung hypoplasia can have long-lasting effects on postnatal lung function, as airway and alveolar formation may be compromised. Preterm birth may also result in incomplete structural development of the lungs as it shortens the period of increased intrauterine lung expansion.

Aeration of the lung and the transition to air-breathing at birth is fundamental to mammalian life and initiates major changes in cardiopulmonary physiology. However, the dynamics of this process and the factors involved are largely unknown, because it has not been possible to observe or measure lung aeration on a breath-by-breath basis. We have used the high contrast and spatial resolution of phase contrast X-ray imaging to study lung aeration at birth in spontaneously breathing neonatal rabbits. As the liquid-filled fetal lungs provide little absorption or phase contrast, they are not visible and only become visible as they aerate, allowing a detailed examination of this process. Pups were imaged live from birth to determine the timing and spatial pattern of lung aeration, and relative levels of lung aeration were measured from the images using a power spectral analysis. We report the first detailed observations and measurements of lung aeration, demonstrating its dependence on inspiratory activity and body position; dependent regions aerated at much slower rates. The air/liquid interface moved toward the distal airways only during inspiration, with little proximal movement during expiration, indicating that trans-pulmonary pressures play an important role in airway liquid clearance at birth. Using these imaging techniques, the dynamics of lung aeration and the critical role it plays in regulating the physiological changes at birth can be fully explored.

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.