Majority of stillbirth cases remain unexplained, suggesting post mortem investigation needs to be refined
Published online; 26 October 2016
Read the articles:
Stillbirth and intrauterine death: factors affecting determination of cause of death at autopsy
Organ weights and ratios for postmortem identification of fetal growth restriction: utility and confounding factors
- Effects of intrauterine retention and postmortem interval on body weight following intrauterine death: implications for assessment of fetal growth restriction at autopsy
- Stillbirth and intrauterine fetal death: role of routine histopathological placental findings to determine cause of death
- Stillbirth and intrauterine fetal death: role of routine histological organ sampling to determine cause of death
- Stillbirth and intrauterine fetal death: contemporary demographic features of >1000 cases from an urban population
Read the press release
: Majority of stillbirth cases remain unexplained, suggesting post mortem investigation needs to be refined. Released 26 October 2016.
Comment from author, Prof. Neil Sebire
'Overall, post mortem examination remains the most effective way of determining how a person has died. However, this research highlights that, in the case of stillbirths, analysing information such as the clinical circumstances and examination of the placenta, without the use of invasive techniques, allows us to get almost as much information. The problem is that using current methods, even including full autopsy, we are still often not able to find out why the baby has died. It’s therefore vitally important that we advance better ways of properly investigating these cases by developing new, more refined techniques. This will ensure we can support families in the best possible way.'
Comment from UOG Editor-in-Chief, Prof. Basky Thilaganathan
'Sebire and colleagues produce convincing data to demonstrate that fetal body weight decreases substantially between intrauterine demise and postnatal weight assessment. This suggests that the majority of stillbirths considered to be small for gestation by birth weight, were likely to have been appropriately sized at the time of death. This finding questions the fundamental rationale and potential effectiveness of current health policy that is solely focused on the detection and elective birth of small fetuses to reduce the risk of stillbirth.'
Pregnant women support first maternal gene therapy trial
Published online; 10 March 2016
Read the article : Ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early-onset fetal growth restriction
Published in Ultrasound of Obstetrics & Gynecology online, 10 March 2016.
Read the press release: Pregnant women support first maternal gene therapy trial. Released 10 March 2016.
Comment from author, Dr Anna David
'The lack of evidence-based treatments for many pregnancy complications is a major problem for pregnant women and their healthcare providers. Severe early-onset fetal growth restriction (FGR) is an example of such a complication. Currently, when a fetus is found to be very small in mid-pregnancy, there is no treatment to improve fetal growth in utero. In order to develop novel maternal and fetal therapies, clinical trials must be carried out that involve pregnant women, but this raises ethical and regulatory issues.'
'The EVERREST consortium aims to carry out the first trial of a novel maternal growth factor gene therapy for severe early-onset FGR. Encouraging data from preclinical studies suggest that increasing growth factor levels in the uteroplacental circulation using gene therapy could safely improve fetal growth. As this would potentially be the first use of gene therapy during pregnancy, the team investigated the ethical and social acceptability of giving gene therapy in a clinical trial to pregnant women. This was not only an important part of EVERREST’s work program but an opportunity to understand more about issues in the development of new pregnancy therapeutics.'
'The authors interviewed women who had experienced a pregnancy affected by severe early-onset FGR. Most women viewed the proposed clinical trial positively and said that they would have wanted the option of participating in a trial. In particular, the women felt that they would have been capable of reaching an autonomous decision about whether to take part in a clinical trial, even at a very difficult time in their pregnancy. Clear information, independent advice and sufficient time for decision making were highlighted as important issues by women and stakeholders. Neither the literature review nor the interviews identified any fundamental objection to the use of gene therapy in pregnancy. This is very encouraging, not just for the EVERREST clinical trial, but also for the development of maternal and fetal therapies more broadly. The study provides a clear message for the clinical and pharmaceutical communities; that women want therapies for pregnancy diseases such as FGR, for which no treatment currently exists.'
New app can help doctors predict the risk of preterm birth
Published; 18 January 2016
Read the article
: Development and validation of a tool incorporating cervical length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high-risk women
Published in UOG, 5 January 2016.
Read the press release: New app can help doctors predict the risk of preterm birth. Released 18 January 2016.
Comment from author, Prof. Andrew Shennan
'Managing and preventing preterm birth remains a major challenge in obstetrics, which causes not only substantial clinical impact but also considerable psychological and financial burden. Most preterm deliveries are due to spontaneous labor, and prediction of those destined to deliver early is key for targeted intervention. There have been significant advances in our understanding of measures to reduce preterm delivery in high-risk women, including vaginal progesterone, cervical cerclage and, more recently, Arabin pessaries. In those likely to deliver, presenting with threatened preterm labor, correctly targeting antenatal steroids reduces unwanted side effects (e.g. fetal weight loss from inappropriate dosage in those that fail to deliver within 7 days) while optimizing benefit if given close to delivery. The use of magnesium sulphate near to delivery can also ameliorate neurological morbidity in the newborn. Tocolysis is sometimes used to facilitate in-utero transfer. All these interventions require judicious assessment of risk, and, clinically, this has proved challenging. Advances in prediction of preterm birth include the use of cervical length measurement and cervicovaginal fetal fibronectin. However, the results of these variables have often been dichotomized in research papers to aid analysis and demonstrate value; this limits their potential as they are continuous variables with variable risk across the measured range. Clinicians’ judgement of risk is also dependent on knowledge and experience, which is also inconsistent.'
'In the January and February issues of UOG, two studies (Kuhrt et al.) have been published that have optimized prediction (in both symptomatic and asymptomatic women) by combining cervical length and the newly quantifiable fetal fibronectin with clinical features in patient history that add to the algorithm. These have been incorporated into an App (download for free: QUiPP) that accurately calculates risk and presents it as a percentage probability of delivering within certain timeframes from testing (within 1, 2 and 4 weeks) and at a range of gestational ages (30, 34 and 37 weeks). The prediction is far more accurate than using the parameters alone and removes the variability of clinicians’ interpretation. The validation sets in both studies confirm the value and generalizability of the prediction tool. The challenge now is to link interventions to the improved knowledge of risk obtained from such tools.'
11 key research priorities to reduce stillbirths
Published; 2nd December 2015
Read the article: Research priorities for stillbirth: process overview and results from UK Stillbirth Priority Setting Partnership
Published in UOG, 2nd December 2015.
Read the press release by Central Manchester Hospitals: Priority Setting Partnership publish 11 key research questions to reduce the number of stillbirths. Released 2nd December 2015.
Read the press release by Tommy’s: Study aims to set priorities for stillbirth research. Released 2nd December 2015.
Comment from UOG Editor-in-Chief, Prof. Basky Thilaganathan
‘Obstetric care has evolved greatly with the introduction of newer technologies and tests to assist in improved screening for adverse pregnancy outcome in the mother and baby. Despite these apparent advances, stillbirth rates continue unabated over the last two decades, at around 1 in every 250 pregnancies. Almost certainly, part of the problem revolves around the fact that clinicians are willing to accept the pseudodiagnosis of 'unexplained stillbirth' in many of these cases - something that would be deemed unacceptable in adulthood. Importantly also, there seems to be an apparent lack of consensus about the direction or strategy for clinical management and future research in this field. New research published in UOG and led by Alex Heazell brought together obstetricians, midwives, parents, third-sector organizations, research funders and pathologists under a Stillbirth Priority Settings Partnership to identify 11 key priorities for research into the reduction of stillbirth and improving care for parents who have experienced a stillbirth. The gathering of information took over 18 months to complete and included over 550 people and dealt with 1200 potential priorities - which was whittled down to 11 priorities and included an emphasis on the content and delivery of health services, optimal bereavement care, maternity care in subsequent pregnancies, responding to symptoms and signs relating to impending stillbirth. There is great hope that the information set out here will provide a solid framework for shaping the stillbirth research agenda in the future.’
Clinical implementation of routine Down-syndrome screening by NIPT
Published online; 26th October 2015
Read the article: Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test.
Published in UOG, online, 26th October 2015
Read the press release : DNA test for Down’s syndrome on the NHS could save lives. Released 26th October 2015.
Comment from UOG Editor-in-Chief, Prof. Basky Thilaganathan
“The use of advanced DNA sequencing technology to screen for Down syndrome in pregnancy has been validated in numerous well conducted research studies over the last 1–2 years. What this pragmatic study adds to the existing literature is to demonstrate convincingly that fetal cell-free DNA testing can be implemented into routine pregnancy care and that it is welcomed by the majority of women who opt to undertake Down syndrome screening. The researchers demonstrate significant reduction in the numbers of invasive prenatal tests - welcomed by women because these tests carry a risk of miscarriage. This reduction in miscarriage risk is not at the expense of detection of Down syndrome because this rate was greater than 90%, as anticipated from previous data. Furthermore, the authors are able to reassure us that, even when a firm diagnosis of Down syndrome is made, about a third of women make the informed decision to continue with their pregnancy, thereby allaying our fears that a safer Down syndrome screening test would lead to increased rates of termination of pregnancy. This study provides the framework for integration of non-invasive prenatal testing into large health organizations.” Professor Basky Thilaganathan, Editor-in-Chief of Ultrasound in Obstetrics & Gynecology.
The role of ultrasound in urogynecology
Published online; 11th March 2014
A randomized controlled trial led by Dr. Svabik in Prague has shown that pelvic floor imaging can be used to accurately identify women most likely to benefit from vaginal mesh surgery.
Read the article: Comparison of vaginal mesh repair with sacrospinous vaginal colpopexy in the management of vaginal vault prolapse after hysterectomy in patients with levator ani avulsion: a randomized controlled trial.
Published in UOG, online, 11th March 2014
Read the press release: Critical trial identifies women most likely to benefit from vaginal mesh surger. Released 11th March 2014
Commentary from author, Dr. K. Svabik
Prague, Czech Republic
"Utilizing ultrasound and imaging in general in urogynecology is still not routine practice. One could compare the situation with the state of perinatology 50 years ago before the introduction of ultrasound when obstetricians would say: “we don’t need ultrasound to deliver babies”. Nowadays, such a viewpoint is almost unimaginable, and there is no doubt that pregnancy outcomes are much better. Perinatology has moved forward due to ultrasound. It has moved from guessing and personal interpretation to knowing and seeing, to prediction on the basis of solid evidence.
"This is exactly what should be happening in urogynecology. We are moving from diagnosis based on clinical skills only to diagnosis through a combination of clinical examination and imaging, towards prediction on the basis of solid evidence, and towards individualisation of therapy. The most important steps is to acknowledge the opportunities provided by imaging and to start using it. Pelvic floor ultrasound is not a complicated technique, and there are many opportunities for teaching and learning.
"We believe that our study is novel and important but, it is still only one stone of a large mosaic.
"Using a noninvasive assessment by pelvic floor ultrasound, we identified patients at high risk of recurrence and used that as entry criterion for our study. This allowed us to demonstrate the benefits of a non-conventional surgical approach in a high- risk group of patients. This reduced risk to patients and saved time and resources. We hope that our results will encourage other centers to use modern diagnostic techniques to optimize study design in surgical intervention trials.This will help provide timely, more accurate and reliable results, at much lower cost. Most importantly, our patients will receive better, faster and more individualized treatment as a result."
Commentary from Dr Hans Peter Dietz
"There is a problem with my chosen subspecialty of Urogynecology. The diagnostic side of the field is rather underdeveloped, to the extent that many common conditions aren’t sought on clinical examination, let alone diagnosed by objective means such as imaging. On the other hand, urogynecologists are very innovative surgeons. We have developed several dozens of new procedures over the last 20 years, some of them highly useful, others questionable. Between 2004 and 2012 a large number of mesh procedures were developed and introduced to prolapse surgery. In retrospect, many thousands of operations were performed on the wrong patients, and some of those patients have suffered serious harm. Since 2006, UOG has published a number of papers and reviews dealing with pre-operative patient selection and with the analysis of mesh complications and failure, but the impact of all this effort has been limited due to a lack of interest from industry and due to the inertia of opinion leaders in our field.
"Svabik et al. are an exception, and they show us how powerful the tools of modern imaging can be when used in the context of a clinical trial. Any new procedure has to be tested in randomised controlled trials. Such trials have to be designed to maximise power and clinical utility, and to minimise risk to patients. A procedure that seems effective in case series needs to be tested in randomised controlled trials, and the first should be undertaken in a high- risk group. This requires a proper diagnostic work-up- in this case with imaging to identify patients with levator avulsion, which has been shown to be the main risk factor for recurrence in multiple studies.
"Svabik et al. based their study design on a well- informed evaluation of the current literature, and the result is there for all to see. While the device tested in this trial, the Anterior Prolift, has been taken from the market due to irregularities with the original FDA approval, alternatives are available to which these results are applicable. Prolapse recurrence is so common in the high- risk patients identified by Svabik et al. that conventional surgery seems pointless, and the increased risk of complications after mesh surgery is easily balanced by the markedly increased cure rate. At the very least such high- risk patients need to be allowed the opportunity to decide for themselves whether they want to risk a 50% higher recurrence rate or a 10% higher rate of complications.
"Unfortunately, the insight exemplified by the Svabik trial is still rather uncommon. Other investigators are spending millions of dollars on studies recruiting thousands of patients using the wrong inclusion criteria, suboptimal interventions and poor outcome measures. The result will be papers in high- impact journals reporting type 2 errors (false- negative findings) due to the dilutional effects of poor study planning. One can only hope that more investigators with the kind of insight displayed by the Prague group will show the folly of such an attitude."
Improved antenatal management protocols impacts survival outcomes in pregnancies complicated by fetal growth restriction
Published online: Monday 23 September 2013
Early results from a large Eurpoean-wide clincial trial that aims to optimise delivery dates for women with high-risk pregnancies complicated by fetal growth restriction reports an increase in survival rates and a reduction in severe mortality compared with similar studies.
Read the article
: Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE). Author: C. Lees et al; ISSUE: Volume 42, Issue 4, pages 400-408; Date: October 2013; Published online: Monday 23 September 2013.
Read the press release : Clinical trial reports improved health and survival outcomes for babies born from high-risk pregnancies. Relesased Monday 23 September 2013
Simple IVF scratching technique improves clinical pregnancy rates by 20%
Published online: Monday 2 September 2013
Results from a randomized control trial demonstrate a significant benefit to the timing of endometrial scratching, reporting an increase in the clinical pregnancy rate of women undergoing IVF and ICSI treatment to 49%, compared with the current average (29%), as well as an increase in the number
of live births, reported at 42%, compared with the current average (23%).
Read the full article: Endometrial scratching performed in the non-transfer
cycle and outcome of assisted reproduction: a randomized controlled trial. Author: CO Nastri et al; ISSUE: Volume 42, Issue 4, pages 375–382; Date: October 2013; Published online: 2 September 2013.
Read the press release: Performing endometrial ‘scratching’ once during IVF treatment can increase clinical pregnancy by 20%. Relesased Sunday 6 October 2013.