Inflammatory Aetiology of Human Myometrial Activation Tested Using Directed Graphs

There are three main hypotheses for the activation of the human uterus at labour: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925), progesterone withdrawal, as a primary event, is plausible (p = 0.499), yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091). DGraph, a software program that creates directed graphs, produced similar results (p = 0.684, p = 0.280, and p = 0.04, respectively). This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible

Moxibustion for cephalic version: a feasibility randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) has been used to correct a breech presentation. Evidence of effectiveness and safety from systematic reviews is encouraging although significant heterogeneity has been found among trials. We assessed the feasibility of conducting a randomised controlled trial of moxibustion plus usual care compared with usual care to promote cephalic version in women with a breech presentation, and examined the views of women and health care providers towards implementing a trial within an Australian context.</p> <p>Methods</p> <p>The study was undertaken at a public hospital in Newcastle, New South Wales, Australia. Women at 34-36.5 weeks of gestation with a singleton breech presentation (confirmed by ultrasound), were randomised to moxibustion plus usual care or usual care alone. The intervention was administered over 10 days. Clinical outcomes included cephalic presentation at birth, the need for ECV, mode of birth; perinatal morbidity and mortality, and maternal complications. Feasibility outcomes included: recruitment rate, acceptability, compliance and a sample size for a future study. Interviews were conducted with 19 midwives and obstetricians to examine the acceptability of moxibustion, and views on the trial.</p> <p>Results</p> <p>Twenty women were randomised to the trial. Fifty one percent of women approached accepted randomisation to the trial. A trend towards an increase in cephalic version at delivery (RR 5.0; 95% CI 0.7-35.5) was found for women receiving moxibustion compared with usual care. There was also a trend towards greater success with version following ECV. Two babies were admitted to the neonatal unit from the moxibustion group. Compliance with the moxibustion protocol was acceptable with no reported side effects. Clinicians expressed the need for research to establish the safety and efficacy of moxibustion, and support for the intervention was given to increase women's choices, and explore opportunities to normalise birth. The sample size for a future trial is estimated to be 381 women.</p> <p>Conclusion</p> <p>Our findings should be interpreted with caution as the study was underpowered to detect statistical differences between groups. Acceptance by women and health professionals towards moxibustion suggest further research is warranted.</p> <p>Trial Registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000985280.aspx">ACTRN12609000985280</a></p

A conversation with the 'breech whisperer'

I (Hannah Dahlen) interviewed Sydney obstetrician and Associate Professor Andrew Bisits to understand how he presents risk and choice to women who have a baby with a breech presentation (i.e. presenting bottom down), where they are making the choice between a vaginal breech birth and a caesarean section. Andrew has now supported over 500 breech births in his career and is known around Australia and internationally for his unique and very woman-centred approach. As you will see in this interview, while Andrew prefers the birth stool for vaginal breech birth as he sees it making the most physiological sense, he is also very clear about being guided by what women want too. Andrew has been coined the ‘baby whisperer’ by our Australian media, but I like to call him the ‘breech whisperer’. I have had the pleasure of knowing and working with Andrew for many years. Whenever I have a client with a breech presentation, we have talked with Andrew. Once one of my clients filmed the external cephalic version (ECV) he did on her and posted it online, it went viral. After a successful ECV, I love sending Andrew pictures (with the woman’s permission) of the woman holding her baby following the birth (mostly at home). He texts back lovely comments like ‘Woohaa Hannah! Delighted for her, pass on my congrats’. His hands have a gentle knowledge that is hypnotic to watch. Perhaps this also comes from a responsiveness he gained playing the violin. Yes, Andrew is an obstetrician who plays the violin, loves a good red wine and tends to get very loud when watching rugby matches (especially if Australia wins). What you read in the following interview is what makes Andrew the way he is and how he presents risk to women when they are deciding what to do with a breech pregnancy at term. If we had more Andrews in the world, we would probably have fewer women seeking to birth outside the system. Andrew not only keeps the proverbial canary in the coal mine singing, he accompanies their song with his violin

Call for special issue of midwifery on risk in childbirth

Editoria

The endocrine regulation of human labour

Placental corticotrophin releasing hormone (CRH) determines the length of pregnancy. CRH drives fetal adrenal production of dehydroepiandrosterone sulfate (DHEAS). DHEAS is converted into estriol in the placenta. Estriol and estradiol are competitive antagonists at equimolar concentrations but both are estrogen agonists at high concentrations. Labor is associated with an excess of estriol over estradiol. High levels of estriol lead to myometrial expression of connexin 43 and cyclo-oxygenase. Myometrial expression of connexin 43 and prostaglandins leads to synchronised myometrial contractions and the onset of labor

PTGS2 (Prostaglandin Endoperoxide Synthase-2) expression in term human amnion in vivo involves rapid mRNA turnover, polymerase-II 5'-pausing, and glucocorticoid transrepression

The in vivo role of glucocorticoids in controlling prostaglandin endoperoxide synthase-2 (PTGS2) expression in the human amnion is unclear despite extensive studies using in vitro models. We addressed this issue by determining PTGS2 mRNA levels and gene transcriptional activity, RNA polymerase-II (pol-II) binding, pol-II C-terminal domain (CTD) phosphorylation, histone acetylation, and histone methylation at the PTGS2 gene in fresh amnion and in amnion explants incubated with dexamethasone for 24 h after delivery, when adaptation from in vivo to in vitro conditions occurred. PTGS2 mRNA turnover changed during incubation involving the initial rapid decrease and subsequent rebound of the transcription rate and stabilization of mRNA. pol-II accumulated in the 5′-region of the gene, which indicated postinitiation pausing. pol-II binding, 5′-accumulation, C-terminal domain Ser-5 and Ser-2 phosphorylation, and histone acetylation decreased rapidly and did not reverse during the transcriptional rebound, suggesting that the transcriptional mechanism altered in vitro. Dexamethasone decreased PTGS2 gene activity and mRNA levels. Glucocorticoid receptor-α (GRα) was bound to the PTGS2 promoter but did not affect pol-II recruitment, pausing, or the epigenetic marks. GRα binding, however, decreased initiating (Ser-5) and elongating (Ser-2) pol-II phosphorylation. The ability of the PTGS2 promoter to bind GRα in response to dexamethasone diminished during incubation. We conclude that PTGS2 mRNA turnover is accelerated in vivo, but the underlying mechanisms are not sustained beyond 24 h in explants. Glucocorticoids chronically transrepress PTGS2 gene activity in vivo in part by interfering with transcription initiation and elongation. Glucocorticoid transrepression of PTGS2 may be important for pregnancy maintenance and the timing of parturition

The development and initiation of the NSW Department of Health interprofessional Fetal welfare Obstetric emergency Neonatal resuscitation Training project

Background: The Fetal Welfare Obstetric emergency Neonatal resuscitation Training (FONT) project was initiated on a background of rising notifications of adverse events in NSW maternity units, the significant proportion of which were related to fetal welfare assessment. Aims: The aim of the study is to describe the development and introduction of the NSW state-wide interprofessional FONT project. Methods: Following development and risk assessment, FONT was launched in February 2008. The project consists of an online component and two face-to-face training days to be completed each 3 years; the first day for fetal welfare assessment and the second for obstetric and newborn emergencies. Eight, 2-day training sessions were conducted throughout NSW for FONT trainers. Each trainer underwent pre-and post-testing for changes in knowledge of fetal welfare assessment. The 2005-2008 NSW adverse event report numbers were assessed. Results: From 20 February to 17 April 2008, 240 trainers had been trained in fetal welfare assessment, and by the end of 2008 these trainers had trained 954 clinicians. There were significant improvements in the interpretation and management planning of electronic fetal heart rate patterns following training. Analysis of Severity Assessment Codes 1 and 2 showed no significant trend in the number of notifications for adverse events related to fetal welfare assessment. Conclusions: In the first 11 months, 25% of the state&apos;s maternity practitioners had received training in the first stage of the FONT project. The FONT project has shown short-term improvements in learning and communication skills and in the participants of the project

Planned home and hospital births in South Australia, 1991-2006 : differences in outcomes

[Letter to the editor