Cardiotocography measures the human fetal heart rate and uterine activity using ultrasound. While it has been a mainstay in antepartum care since the 1960s, cardiotocograms consist of complex signals that have proven difficult for clinicians to interpret accurately and as such clinical inference is often difficult and unreliable. Previous attempts at codifying approaches to analyzing the features within these signals have failed to demonstrate reliability or gain sufficient traction. Since the early 1990s, the Dawes-Redman system of automated computer analysis of cardiotocography signals has enabled robust analysis of cardiotocographic signal features, employing empirically-derived criteria for assessing fetal wellbeing in the antepartum. Over the past 30 years, the Dawes-Redman system has been iteratively updated, now incorporating analyses from over 100,000 pregnancies. In this review, we examine the history of cardiotocography, signal processing methodologies and feature identification, the development of the Dawes-Redman system, and its clinical applications.

Cardiotocography measures the human fetal heart rate and uterine activity using ultrasound. While it has been a mainstay in antepartum care since the 1960s, cardiotocograms consist of complex signals that have proven difficult for clinicians to interpret accurately and as such clinical inference is often difficult and unreliable. Previous attempts at codifying approaches to analyzing the features within these signals have failed to demonstrate reliability or gain sufficient traction. Since the early 1990s, the Dawes-Redman system of automated computer analysis of cardiotocography signals has enabled robust analysis of cardiotocographic signal features, employing empirically-derived criteria for assessing fetal wellbeing in the antepartum. Over the past 30 years, the Dawes-Redman system has been iteratively updated, now incorporating analyses from over 100,000 pregnancies. In this review, we examine the history of cardiotocography, signal processing methodologies and feature identification, the development of the Dawes-Redman system, and its clinical applications.

The syncytiotrophoblast, a fused single-cell layer between mother and fetus, constitutively releases extracellular vesicles (STBEV) directly into the maternal circulation. STBEV contain a variety of proteins and RNA which can be targeted to specific cells. In preeclampsia, asymptomatic placental oxidative stress is a precursor to later multi-organ dysfunction in the mother. Increased STBEV release in preeclampsia is considered a manifestation of syncytiotrophoblast stress, which may play a key role in signaling between fetus and mother. STBEV release in preeclampsia changes, both in terms of volume and content. In this review, we outline the latest advances in STBEV isolation and detection. We consider evidence for differential STBEV release, protein cargo and RNA content in preeclampsia, highlighting common pitfalls in study design. We summarise studies to date demonstrating STBEV actions on target cells. Ultimately, we consider how STBEV fit into the pathophysiology of the heterogeneous syndrome of preeclampsia. The key unifying concept in early- and late-onset preeclampsia is syncytiotrophoblast stress. We submit that STBEV are the key stress signal in preeclampsia. We believe that further investigation of STBEV release, content, and actions may offer valuable insights into preeclampsia pathophysiology and potential new clinical diagnostics and therapeutic targets.

The syncytiotrophoblast, a fused single-cell layer between mother and fetus, constitutively releases extracellular vesicles (STBEV) directly into the maternal circulation. STBEV contain a variety of proteins and RNA which can be targeted to specific cells. In preeclampsia, asymptomatic placental oxidative stress is a precursor to later multi-organ dysfunction in the mother. Increased STBEV release in preeclampsia is considered a manifestation of syncytiotrophoblast stress, which may play a key role in signaling between fetus and mother. STBEV release in preeclampsia changes, both in terms of volume and content. In this review, we outline the latest advances in STBEV isolation and detection. We consider evidence for differential STBEV release, protein cargo and RNA content in preeclampsia, highlighting common pitfalls in study design. We summarise studies to date demonstrating STBEV actions on target cells. Ultimately, we consider how STBEV fit into the pathophysiology of the heterogeneous syndrome of preeclampsia. The key unifying concept in early- and late-onset preeclampsia is syncytiotrophoblast stress. We submit that STBEV are the key stress signal in preeclampsia. We believe that further investigation of STBEV release, content, and actions may offer valuable insights into preeclampsia pathophysiology and potential new clinical diagnostics and therapeutic targets.