A distinctive pattern of recurrent rapid falls in fetal heart rate, called decelerations, are commonly associated with uterine contractions during labour. These brief decelerations are mediated by vagal activation. The reflex triggering this vagal response has been variably attributed to a mechanoreceptor response to fetal head compression, to baroreflex activation following increased blood pressure during umbilical cord compression, and/or a Bezold–Jarisch reflex response to reduced venous return from the placenta. Although these complex explanations are still widespread today, there is no consistent evidence that they are common during labour. Instead, the only mechanism that has been systematically investigated, proven to be reliably active during labour and, crucially, capable of producing rapid decelerations is the peripheral chemoreflex. The peripheral chemoreflex is triggered by transient periods of asphyxia that are a normal phenomenon associated with all uterine contractions. This should not cause concern as the healthy fetus has a remarkable ability to adapt to these repeated but short periods of asphyxia. This means that the healthy fetus is typically not at risk of hypotension and injury during uncomplicated labour even during repeated brief decelerations. The physiologically incorrect theories surrounding decelerations that ignore the natural occurrence of repeated asphyxia probably gained widespread support to help explain why many babies are born healthy despite repeated decelerations during labour. We propose that a unified and physiological understanding of intrapartum decelerations that accepts the true nature of labour is critical to improve interpretation of intrapartum fetal heart rate patterns.

The fetus is consistently exposed to repeated periods of impaired oxygen (hypoxaemia) and nutrient supply in labour. This is balanced by the healthy fetus's remarkable anaerobic tolerance and impressive ability to mount protective adaptations to hypoxaemia. The most important mediator of fetal adaptations to brief repeated hypoxaemia is the peripheral chemoreflex, a rapid reflex response to acute falls in arterial oxygen tension. The overwhelming majority of fetuses are able to respond to repeated uterine contractions without developing hypotension or hypoxic-ischaemic injury. In contrast, fetuses who are either exposed to severe hypoxaemia, for example during uterine hyperstimulation, or enter labour with reduced anaerobic reserve (e.g. as shown by severe fetal growth restriction) are at increased risk of developing intermittent hypotension and cerebral hypoperfusion. It is remarkable to note that when fetuses develop hypotension during such repeated severe hypoxaemia, it is not mediated by impaired reflex adaptation, but by failure to maintain combined ventricular output, likely due to a combination of exhaustion of myocardial glycogen and evolving myocardial injury. The chemoreflex is suppressed by relatively long periods of severe hypoxaemia of 1.5-2 min, longer than the typical contraction. Even in this setting, the peripheral chemoreflex is consistently reactivated between contractions. These findings demonstrate that the peripheral chemoreflex is an indefatigable guardian of fetal adaptation to labour.

Key pointsr Fetal heart rate variability and changes in the ST segment of the electrocardiogram are used clinically during labour to identify fetuses at risk of severe metabolic acidosis or death.r Sympathetic nervous system activity contributes to heart rate variability in healthy normoxic fetuses, and is critical for the rapid haemodynamic adaptations to repeated episodes of asphyxia induced by brief complete umbilical cord occlusions at rates consistent with active labour.r We now show that chemical sympathectomy did not alter fetal heart rate variability between episodes of brief repeated asphyxia or elevation of the ST segment during asphyxia.r The lack of influence of the sympathetic system on fetal heart rate variability between episodes of brief asphyxia suggests that measures of fetal heart rate variability are unlikely to help monitor changes in sympathetic nervous system activity during active labour.Abstract Changes in fetal heart rate variability (FHRV) and ST segment elevation (measured as the T/QRS ratio) are used to evaluate fetal adaptation to labour. The sympathetic nervous system (SNS) is an important contributor to FHRV under healthy normoxic conditions, and is critical for rapid support of blood pressure during brief labour-like asphyxia. However, although it has been assumed that SNS activity contributes to FHRV during labour; this has never been tested, and it is unclear whether the SNS contributes to the rapid increase in T/QRS ratio during brief asphyxia. Thirteen chronically instrumented fetal sheep at 0.85 of gestation received either chemical sympathectomy with 6-hydroxydopamine (6-OHDA; n = 6) or sham treatment (control; n = 7), followed 4-5 days later by 2 min episodes of complete umbilical cord occlusion repeated every 5 min for up to 4 h, or until mean arterial blood pressure fell to <20 mmHg for two successive occlusions. FHRV was decreased before occlusions in the 6-OHDA group (P < 0.05) and 2-4.5 h during recovery after occlusions (P < 0.05) compared to the control group. During each occlusion there was a rapid increase in T/QRS ratio. Between successive occlusions the T/QRS ratio rapidly returned to baseline, and FHRV increased above baseline in both groups (P < 0.05), with no significant effect of sympathectomy on FHRV or T/QRS ratio. In conclusion, these data show that SNS activity does not mediate the increase in FHRV between repeated episodes of brief umbilical cord occlusion or the transient increase in T/QRS ratio during occlusions. Abbreviations 6-OHDA, 6-hydroxydopamine; FHR, fetal heart rate; FHRV, fetal heart rate variability; MAP, mean arterial pressure; RMSSD, root mean square of successive RR intervals; SDNN, standard deviation of RR intervals; SNS, sympathetic nervous system; STV, short-term variation.

Therapeutic hypothermia significantly improves survival without disability in near-term and full-term newborns with moderate to severe hypoxic-ischaemic encephalopathy. However, hypothermic neuroprotection is incomplete. The challenge now is to find ways to further improve outcomes. One major limitation to progress is that the specific mechanisms of hypothermia are only partly understood. Evidence supports the concept that therapeutic cooling suppresses multiple extracellular death signals, including intracellular pathways of apoptotic and necrotic cell death and inappropriate microglial activation. Thus, the optimal depth of induced hypothermia is that which effectively suppresses the cell death pathways after hypoxia-ischaemia, but without inhibiting recovery of the cellular environment. Thus mild hypothermia needs to be continued until the cell environment has recovered until it can actively support cell survival. This review highlights that key survival cues likely include the inter-related restoration of neuronal activity and growth factor release. This working model suggests that interventions that target overlapping mechanisms, such as anticonvulsants, are unlikely to materially augment hypothermic neuroprotection. We suggest that further improvements are most likely to be achieved with late interventions that maximise restoration of the normal cell environment after therapeutic hypothermia, such as recombinant human erythropoietin or stem cell therapy.

Hypoxia-ischemia, infection/inflammation, and barotrauma/volutrauma all contribute to preterm brain injury. Multiple different triggers of preterm brain injury are associated with central nervous system dysmaturation. Secondary brain inflammation may be a viable target to improve neurodevelopment after preterm birth.