Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria.

Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks' gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24-34 weeks' gestation); two prospective cohorts collected on the day of delivery (36 + 3-41 + 3 weeks' gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses.

Extracellular Vesicles and Preeclampsia: Current Knowledge and Future Research Directions.

Preeclampsia (PE) is associated with long-term morbidity in mothers and lifelong morbidities for their children, ranging from cerebral palsy and cognitive delay in preterm infants, to hypertension, diabetes and obesity in adolescents and young adults. There are several processes that are critical for development of materno-fetal exchange, including establishing adequate perfusion of the placenta by maternal blood, and the formation of the placental villous vascular tree. Recent studies provide persuasive evidence that placenta-derived extracellular vesicles (EVs) represent a significant intercellular communication pathway, and that they may play an important role in placental and endothelial cell (both fetal and maternal) function. These functions are known to be altered in PE. EVs can carry and transport a wide range of bioactive molescules that have potential to be used as biomarkers and therapeutic delivery tools for PE. EV content is often parent cell specific, thus providing an insight or "thumbprint" of the intracellular environment of the originating cell (e.g., human placenta). EV have been identified in plasma under both normal and pathological conditions, including PE. The concentration of EVs and their content in plasma has been reported to increase in association with disease severity and/or progression. Placenta-derived EVs have been identified in maternal plasma during normal pregnancy and PE pregnancies. They contain placenta-specific proteins and miRNAs and, as such, may be differentiated from maternally-derived EVs. The aim of this review, thus, is to describe the potential roles of EVs in preecmpatic pregnancies, focussing on EVs secreted from placental cells. The biogenesis, specificity of placental EVs, and methods used to characterise EVs in the context of PE pregnancies will be also discussed.

Female genital mutilation: Obstetric outcomes in metropolitan Sydney.

BACKGROUND: Female genital mutilation (FGM) and its impact on women's health are becoming relevant in Australia due to increases in numbers of refugees and migrants from affected countries. Notwithstanding the psychological trauma from FGM, there is a broad range of sequelae relevant to obstetrics and gynaecology, particularly related to maternal morbidity from labour and delivery. AIMS: To assess the prevalence of FGM in our unit and document its effect on maternal and neonatal outcomes. METHODS: Retrospective cohort study of women affected by FGM who delivered at a metropolitan hospital in Sydney over a five-year period. The primary outcome was mode of delivery and secondary outcomes addressed maternal morbidity and neonatal nursery admission compared with women unaffected by FGM. RESULTS: A full data set was available for 141/142 women affected by FGM. The overall prevalence of FGM was 1.64%. The majority of women affected by FGM were documented to have FGM 3 (41.1%). There was no difference in caesarean section rate. Women with FGM were less likely to be delivered by vacuum or forceps (11.1% vs 2.8%; P = 0.0009). There was no difference in perineal trauma, postpartum haemorrhage and neonatal nursery admission. Women with FGM 3 were more likely to have an episiotomy (4.8% vs 25.9%; P = 0.0007) without an increase in anal sphincter injury (P = 0.7). Documentation complying with local policy and guidelines was poor. CONCLUSIONS: FGM is increasingly common in Australia. This study adds to the Australian literature quantifying the effects on obstetric outcomes in these high-risk women.

Brugada syndrome.

As a clinical entity the Brugada syndrome has existed since 1992 and has been associated with a high risk of sudden cardiac death predominately in younger males. Patients can present with symptoms (ie syncope, palpitations, aborted sudden cardiac death) and asymptomatically. Its three characteristic electrocardiographic patterns can occur both spontaneously or after provocation with sodium channel-blocking agents. Risk stratification and the need for treatment depend on the patient's symptoms, electrocardiography, family history, and electrophysiological inducibility to discern if treatment by implantable cardioverter defibrillator, the only effective treatment to date, is appropriate. This review focuses on Brugada syndrome and various aspects of the disease including proposed mechanisms, epidemiology, clinical presentations, genetics, diagnosis, risk stratification, and treatment options.