The peripheral chemoreflex and fetal defenses against intrapartum hypoxic-ischemic brain injury at term gestation.

Fetal hypoxemia is ubiquitous during labor and, when severe, is associated with perinatal death and long-term neurodevelopmental disability. Adverse outcomes are highly associated with barriers to care, such that developing countries have a disproportionate burden of perinatal injury. The prevalence of hypoxemia and its link to injury can be obscure, simply because the healthy fetus has robust coordinated defense mechanisms, spearheaded by the peripheral chemoreflex, such that hypoxemia only becomes apparent in the minority of cases associated with stillbirth, severe metabolic acidemia or adverse neurodevelopmental outcomes.

Toward a Cenozoic history of atmospheric CO.

The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO record spanning the past 66 million years.

An Update of Our Understanding of Fetal Heart Rate Patterns in Health and Disease.

UNDERSTANDING FETAL HEART RATE PATTERNS THAT MAY PREDICT ANTENATAL AND INTRAPARTUM NEURAL INJURY: Christopher A. Lear, Jenny A. Westgate, Austin Ugwumadu, Jan G.

The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep.

Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax.

Prediction of Fetal Blood Pressure during Labour with Deep Learning Techniques.

Our objective is to develop a model for the prediction of minimum fetal blood pressure (FBP) during fetal heart rate (FHR) decelerations. Experimental data from umbilical occlusions in near-term fetal sheep (2698 occlusions from 57 near-term lambs) were used to train a convolutional neural network. This model was then used to estimate FBP for decelerations extracted from the final 90 min of 53,445 human FHR signals collected using cardiotocography.

Circadian patterns of heart rate variability in fetal sheep after hypoxia-ischaemia: A biomarker of evolving brain injury.

Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.

Dissecting the contributions of the peripheral chemoreflex and myocardial hypoxia to fetal heart rate decelerations in near-term fetal sheep.

Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of myocardial hypoxia, but the relative contribution of these two mechanisms and how this balance changes with evolving fetal compromise remain unknown. In the present study, chronically instrumented near-term fetal sheep received surgical vagotomy (n = 8) or sham vagotomy (control, n = 11) to disable the peripheral chemoreflex and unmask myocardial hypoxia. One-minute complete umbilical cord occlusions (UCOs) were performed every 2.

Magnesium sulphate reduces tertiary gliosis but does not improve EEG recovery or white or grey matter cell survival after asphyxia in preterm fetal sheep.

Maternal magnesium sulphate (MgSO ) treatment is widely recommended before preterm birth for neuroprotection. However, this is controversial because there is limited evidence that MgSO provides long-term neuroprotection. Preterm fetal sheep (104 days gestation; term is 147 days) were assigned randomly to receive sham occlusion with saline infusion (n = 6) or i.

Evolution of grey matter injury over 21 days after hypoxia-ischaemia in preterm fetal sheep.

Reduced grey matter volume in preterm infants is associated with later disability, but its time course and relationship with white matter injury are not well understood. We recently showed that moderate-severe hypoxia-ischaemia (HI) in preterm fetal sheep led to severe cystic injury 2-3 weeks later. In the same cohort we now show profound hippocampal neuronal loss from 3 days after HI.

Fetal heart rate responses in chronic hypoxaemia with superimposed repeated hypoxaemia consistent with early labour: a controlled study in fetal sheep.

Objective: Deceleration area (DA) and capacity (DC) of the fetal heart rate can help predict risk of intrapartum fetal compromise. However, their predictive value in higher risk pregnancies is unclear. We investigated whether they can predict the onset of hypotension during brief hypoxaemia repeated at a rate consistent with early labour in fetal sheep with pre-existing hypoxaemia.

Alpha-adrenergic receptor activation after fetal hypoxia-ischaemia suppresses transient epileptiform activity and limits loss of oligodendrocytes and hippocampal neurons.

Exposure to hypoxic-ischaemia (HI) is consistently followed by a delayed fall in cerebral perfusion. In preterm fetal sheep this is associated with impaired cerebral oxygenation, consistent with mismatch between perfusion and metabolism. In the present study we tested the hypothesis that alpha-adrenergic inhibition after HI would improve cerebral perfusion, and so attenuate mismatch and reduce neural injury.

Tumour necrosis factor blockade after asphyxia in foetal sheep ameliorates cystic white matter injury.

Cystic white matter injury is highly associated with severe neurodevelopmental disability and cerebral palsy in preterm infants, yet its pathogenesis remains poorly understood and there is no established treatment. In the present study, we tested the hypothesis that slowly evolving cystic white matter injury after hypoxia-ischaemia is mediated by programmed necrosis initiated by tumour necrosis factor. Tumour necrosis factor blockade was begun 3 days after hypoxia-ischaemia to target the tertiary phase of injury, when most secondary cell death is thought to be complete.

Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia.

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment.

Increased variability of fetal heart rate during labour: a review of preclinical and clinical studies.

Increased fetal heart rate variability (FHRV) in intrapartum cardiotocographic recording has been variably defined and poorly understood, limiting its clinical utility. Both preclinical (animal) and clinical (human) evidence support that increased FHRV is observed in the early stage of intrapartum fetal hypoxaemia but can also be observed in a subset of fetuses during the preterminal stage of repeated hypoxaemia. This review of available evidence provides data and expert opinion on the pathophysiology of increased FHRV, its clinical significance and a stepwise approach regarding the management of this pattern, and propose recommendations for standardisation of related terminology.

Fetal heart rate variability is a biomarker of rapid but not progressive exacerbation of inflammation in preterm fetal sheep.

Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation.