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Understanding the physiology of immediate and delayed umbilical cord clamping at birth: Need for evidence‐based pathway to reduce confusion

The rationale for the study by Smolich & Kenna (2022) is straightforward, based on the need to obtain a more complete picture of perinatal arterial blood flow differences and similarities between delayed cord clamping (DCC) and ICC. Thus, the study by Bhatt et al. (2013) was specifically related to comparison between initial ventilation with DCC and ICC with an extended (∼2 min) interval prior to ventilation. However, because potential effects of an extended ICC-to-ventilation interval on perinatal haemodynamics were not even considered, the findings of Bhatt et al. (2013) have beenwidely applied in a blanket manner to promote the view that the use of ICC leads to haemodynamic instability in the birth transition, whereas DCC does not. For example, an Editorial introduction to Hooper, Polglase et al. (2015) stated that ‘This article focuses on the startling haemodynamic disturbances that result from completely obstructing the placental circulation before an infant has started to breathe. The effect is to cause marked swings in cardiac output, blood pressure and oxygenation that are largely avoided when cord clamping is delayed until after breathing is established’ (Stenson, 2015). Such generalizations have not been supported by later findings, which suggest that it is not ICC per se that results in haemodynamic instability during the birth transition, but rather the interval between ICC and the start of ventilation (Smolich et al., 2015, 2017). Thus, ICC prior to ventilation is followed by a very rapid decline in arterial oxygenation, which reaches an asphyxial level by 45−60 s after ICC (Smolich et al., 2015, 2017, Smolich, Kenna et al., 2021). This asphyxial level of arterial oxygenation is accompanied by exponential rises in circulating concentrations of the catecholamines noradrenaline and adrenaline, which play a major role in surges of heart rate, blood pressure and cardiac contractility initially evident after birth (Smolich et al., 2017). This is in stark contrast to an unchanged heart rate, a fall in arterial blood pressure and relatively minor changes in cardiac contractility present after birth following a non-asphyxial (<45 s) ICC-to-ventilation interval (Smolich et al., 2017, 2019). Importantly, these very different haemodynamic responses between asphyxial and non-asphyxial ICC-to-ventilation intervals are quite consistent with the effects of complete occlusion of the umbilical cord using a balloon occluder in chronicallyinstrumented fetal lambs, where release of the balloon after a 2 min occlusion is followed by surges in heart rate and arterial blood pressures (e.g. figs. 2A and 3A in Lear et al., 2020), which do not occur with balloon release following a 1 min occlusion (e.g. fig. 1A and B in Lear et al., 2021). In accord with the clinical references cited by Hooper et al. (2022), the foregoing imply that a spectrum of ICC-to-ventilation intervals can occur during the birth transition. It is therefore important to understand how blood flow accompaniments at both ends of this spectrum compare with those of DCC, particularly given that perinatal heart rate, arterial blood pressure and cardiac contractility responses differ so markedly between asphyxial and non-asphyxial ICC-to-ventilation intervals (Smolich et al., 2015, 2017). The study by Bhatt et al. (2013) compared DCC with ICC and an asphyxial (albeit unrecognized) ICC-to-ventilation interval. The study by Smolich and Kenna (2022) has extended the findings to ICC with a non-asphyxial ICC-to-ventilation interval, comprising the other end of the spectrum. It is surprising that Hooper et al. (2022) state that a brief non-asphyxial interval between ICC and ventilation is ‘unrealistic’, given that this is precisely the type of interval that was employed in their recent study in fetal lambs on use of cord milking at birth (Blank et al., 2018). Importantly, fig. 1C of Blank et al. (2018) demonstrates the very response underlying the rationale for the study by Smolich and Kenna (2022), namely that, after ICC followed by an∼30 s interval prior to ventilation, heart rate was unchanged and arterial blood pressure fell following the start of ventilation, which is similar to findings observed after a ∼40 s ICC-to-ventilation interval (Smolich et al., 2015, 2017, 2019).