Something worth waiting for: is delayed cord clamping always beneficial?

Abstract

The transition of the fetus to newborn life involves a number of physiological changes, specifically to the respiratory and cardiovascular systems. Prior to birth, the fetus receives well-oxygenated blood from the placenta via the umbilical vein, with no gas exchange occurring at the fluid-filled lungs. To ensure that not all the blood entering the right side of the fetal heart is sent towards the lungs as it would be after birth, the fetal circulation includes unique shunts: the foramen ovale (FO) and the ductus arteriosus (DA). The FO exists between the atria and allows well-oxygenated blood entering from the inferior vena cava to be preferentially shunted from the right to the left side of the heart, while the DA ensures the majority of right ventricular cardiac output bypasses the pulmonary circulation to instead join the blood flow within the descending aorta. Consequently, during fetal life only ∼7–8% of combined ventricular cardiac output perfuses the lungs (Rudolph, 1985). At birth, the lungs replace the function of the placenta in oxygenating the blood, and the neonatal circulation changes with closure of the DA and FO. When these circulatory changes do not occur, oxygenated and deoxygenated blood is mixed.ApatentDA leads to poor peripheral perfusion, tachycardia and pulmonary hypertension. As a result, there is much interest in the regulation of these circulatory changes at the time of birth and more specifically how to ensure that they occur in an appropriate timeframe to mitigate and prevent poor neonatal outcomes. Both the cessation of blood flow from the placenta and the start of respiration are stimuli to cause these cardiovascular changes in the newborn. Recently, studies have begun to explore the impact of the relative timing of these two stimuli on neonatal physiology. Historically, the cord is clamped immediately (ICC) after delivery, and the newborn subsequently begins breathing. However, current clinical practice is shifting to delay the clamping of the cord until after ventilation has begun (DCC) and potentially allow an easier switch from blood oxygenation at the placenta to oxygenation in the lungs. This could be more effective in preterm babies with a more immature cardiopulmonary circuitry. Practice guidelines developed by the International Liaison Committee on Resuscitation (ILCOR) recommend at least 30 s delay before cord clamping postpartum in preterm newborns (<34+0 weeks gestational age) not requiring immediate resuscitation (Costa-Nobre et al., 2021). This recommendation is due to improved clinical outcomes with DCC, including improved cardiovascular transition, reduced risks of intraventricular haemorrhage and necrotising enterocolitis, and higher haemoglobin and haematocrit. Additionally, DCC in preterm infants reduces mortality, with the number needed to benefit of 20 (Fogarty et al., 2018). Importantly, there is no recommendation for DCC when infants need immediate resuscitation. This Journal Club focuses on a recently published study by Smolich and Kenna in The Journal of Physiologywhich explores the interaction between timing to ventilation and the timing of cord clamping in preterm lambs (Smolich & Kenna, 2022). The article compares the haemodynamics of DCC against ICC, using a non-asphyxial ∼40 s interval between clamping and ventilation in preterm lambs (Smolich & Kenna, 2022). Previously Bhatt et al. (2013) delayed ventilation by an asphyxial ∼2 min after ICC, which Smolich and Kenna argue as being twice as long a duration of asphyxia than would be clinically recommended: ventilation within 1 min of birth. Smolich and Kenna hypothesised that there would be differences in central arterial blood flow patterns when comparing ICC and DCC with a shorter interval to ventilation, though the direction of change was not stated. A previous study in lambs delivered at 126 days gestation (term ∼147 days gestation), a preclinical model for a very preterm infant, demonstrated a smoother cardiovascular transition in DCC than ICC lambs (Bhatt et al., 2013). Compared to the ICC lambs, the magnitude of changes in carotid artery blood pressure, pulmonary blood pressure, carotid artery blood flow, heart rate and right ventricular output were reduced in DCC lambs. Furthermore, greater pulmonary blood flow and right ventricular output were observed across the entire 30 min protocol following birth in the DCC group, indicative of a prolonged benefit. Consequently, the authors state that DCC may be beneficial for preterm neonates requiring resuscitation as well as the healthy term neonate. However, the beneficial effects may be muted with a shorter time between ICC and ventilation, which is explored by Smolich & Kenna (2022). Smolich and Kenna studied 20 ewes that were anaesthetised at 128 days of gestation (term = 147 days gestation) and the fetus delivered. It is not explicit how the ICC and DCC groups were allocated or how and why only one fetus was selected from a multiple pregnancy. Whilst the placental circulation remained intact, catheters were surgically placed in the superior vena cava, brachiocephalic trunk, pulmonary trunk and left atrium of each fetus. Flow probes were inserted into the fetal brachiocephalic trunk, aortic isthmus, ductus arteriosus and left pulmonary artery. The ICC group (n = 10) had the cord clamped directly after delivery and were ventilated ∼40 s later. The DCC group (n = 10) were ventilated immediately following delivery and the cord was clamped ∼90 s later. Initial ventilator settings were positive end expiratory pressure was 8 cmH2O, respiratory rate 60 breaths per minute, tidal volume 7 mL/kg and fraction of inspired oxygen concentration 30%. Ventilator settings were adjusted to maintain a preductal SpO2 of 85–95% measured by pulse oximetry. Haemodynamic measurements, ventricular outputs, blood pressures and blood flow were recorded periodically