Maternal health

Giving progesterone in early pregnancy may reduce preeclampsia risk – preliminary study

Written by Louise Stanley on 17/11/2023. Posted in Maternal health.

Prescribing vaginal progesterone treatment early in pregnancy appears to reduce risk of developing preeclampsia – a potentially fatal condition – by approximately 39%, a recent research review suggests.

Collaborating through the Tommy’s National Centre for Miscarriage Research, Dr Pedro Melo from the University of Oxford, and Dr Adam Devall and Professor Arri Coomarasamy from BHP member the University of Birmingham have analysed the findings of 11 recent studies involving 11,640 women.

These studies were originally designed to explore the impact of progesterone on reducing miscarriage or preterm birth rates. In every study, data were also collected on whether the same treatment affected rates of preeclampsia or other high blood pressure (hypertensive) disorders in women during pregnancy.

The review, published in the British Journal of Obstetrics and Gynaecology, concludes that vaginal progesterone appears to reduce risk of hypertensive disorders in pregnancy, but only when treatment is started in the first trimester.

The review showed that, compared to a placebo, 400 mg of vaginal progesterone used twice a day was associated with a 39% reduction in preeclampsia and a 29% reduction in the rate of other hypertensive disorders such as gestational hypertension.

Starting progesterone early in pregnancy appears to be critical: no clear evidence was found through this review to suggest that starting progesterone in the second or third trimesters had an effect.

Frequency, quantity, and method of use are also important: 400 mg used twice daily as a vaginal capsule showed a benefit in reducing risk of preeclampsia and other hypertensive disorders but using 400 mg once a day did not.

“The recent PROMISE and larger PRISM trials led to an exciting breakthrough in finding evidence that progesterone can reduce miscarriage risk in some women when used in the first trimester. This evidence led to updated NICE guidelines in 2021 recommending its use. But the signal we found in the data for progesterone’s effectiveness in reducing hypertensive disorders had not previously been demonstrated.

“These are exciting preliminary findings, but it must be stressed that they were secondary results of trials focusing on the use of progesterone for the prevention of miscarriage and preterm birth, not preeclampsia. We need a large randomised controlled trial focusing specifically on women and birthing people at risk of preeclampsia to confirm our hypothesis that progesterone supplementation may tackle abnormal implantation in this subgroup of people” said Dr Pedro Melo, lead author of the study at the Tommy’s National Centre for Miscarriage Research at the University of Birmingham and the Nuffield Department of Women’s and Reproductive Health at the University of Oxford.

Dr Adam Devall, Institute of Metabolism and Systems Research, University of Birmingham, added: “The preliminary finding from this study suggests vaginal micronised progesterone might reduce the risk of preeclampsia. The researchers are calling for a large multi-centre clinical trial to explore the effects of progesterone in women at risk of preeclampsia.”

The 11 studies analysed focused on groups of pregnant women who either had a history of recurrent pregnancy loss or had a threatened miscarriage (i.e., they were experiencing early pregnancy bleeding). The review recommends that future studies are needed to explore the link further, to find out whether the reductions of 29-39% are relevant to all women and birthing people and whether the effect could be larger for those who have risk factors for preeclampsia.

Preeclampsia is a condition that affects some pregnant women, usually during the second half of pregnancy or soon after their baby is delivered. Preeclampsia can lead to fetal growth restriction which can cause premature birth. If severe, it can be dangerous, sometimes even fatal, for mothers.

Progesterone plays an important role in implantation of the embryo as it helps make the tissue lining the uterus receptive to implantation. By giving vaginal progesterone, researchers believe it is possible to combat problems with the lining of the womb and partly correct abnormal implantation, helping support successful development of the blood vessels in the placenta. This would reduce the chance of developing conditions such as preeclampsia.

“This research further supports Tommy’s calls for women with a history of miscarriage and pregnancy bleeding to be given progesterone in the early stages of pregnancy. We must continue to keep exploring progesterone’s potential and improve understanding of what it can be used for, who it works best for, when, and how” explained Kate Davies, Research Director at Tommy’s.

Healthy Mum, Healthy Baby, Healthy Future – a year on, what progress has been made?

Written by Louise Stanley on 26/06/2023. Posted in Maternal health.

“We cannot allow another 40 years to pass by with no new medicines for pregnant women” – Professor Katie Morris reflects on BHP’s Pregnancy Policy Commission and its work since the publication of the Healthy Mum, Healthy Baby, Healthy Future report in 2022.

Most pregnant women will have a healthy pregnancy and give birth to healthy babies. An increasing number of women, however, will either have one or more health conditions before they become pregnant which require on-going treatment, or they may develop complications of pregnancy which require treatment.

The care of these women is severely hampered by a lack of suitable medicines, that we definitively know to be safe and effective for use in pregnancy or during breastfeeding. As a consequence, women and babies worldwide continue to become sick and die during or immediately after pregnancy. Despite this, over the last 40 years, only two new medicines have been approved for use in pregnancy.

Birmingham Health Partners‘ 2021 report, ‘Safe and Effective Medicines for Use in Pregnancy: A Call to Action’ highlighted the absence of research and information on the safety of medicines in pregnancy. It also drew attention to the urgent health needs of this neglected group both nationally and internationally, and the potential for saving and improving millions of lives globally.

As a direct response to this report the University of Birmingham and Birmingham Health Partners convened a Policy Commission focussing on the UK, canvassing knowledge and opinions from key parties including patient groups, the pharmaceutical industry, scientists, clinicians, NHS leaders, regulators and insurers. It aimed to explore the scale of the problems that are preventing the evaluation and development of safe medicines for use in pregnancy and collected recommendations for how these could be overcome.

The Commission report was published in May 2022 and entitled “Healthy Mum, Healthy Baby, Healthy Future.” It made a series of eight recommendations related to advocacy, widening participation of pregnant women in clinical trials, updating information on existing medicines, de-risking the insurance process for clinical trials, incentivising industry to develop pregnancy specific medicines, establishing a UK-wide network of research centres, improving the use of routine data, and appointing a UK steering committee to deliver these recommendations.

Over the last year, members of the Commission have been working to develop the steering group and engage with industry and insurance companies to drive forward these recommendations. There are challenges in driving this agenda forwards which can be broadly described as a de-prioritisation of women’s health, and particularly pregnancy, by industry and in the delivery of clinical trials related to workforce and capacity.

Without combined efforts from all stakeholders; public, scientific, clinical, industry, regulatory and governmental sectors, we will not see any progress. The first step will be through co-ordinated efforts via the recently formed steering committee and renewed approaches for engagement with industry and insurance providers.

We cannot allow another 40 years to pass by with no new medicines for pregnant women.

Together these stakeholders must advocate for change, respond to research and funding issues, and, where necessary, work to change official guidance or law to enable progress in this much neglected area.

The UK is well placed to become a global pioneer of maternal health research innovation. We have the health infrastructure of our NHS, with its birth-to-death records. Our medicines regulator is able to fast-track drug development and make changes to streamline the process, as well as working globally with Europe, the US and other regions. We are already a global hub for insurance – and we can support and build on this to add to our potential in becoming a leader in clinical studies for medicines in pregnancy.

There is an urgent need for action to address the underserved area of medicines use in pregnancy. Without it, women and babies will continue to die when they could be saved. They will continue to experience long-term health effects, disability and distress, which might be avoided. It is no longer ethical to deny pregnant women and their unborn babies access to safe, modern medicines that the rest of the population enjoys.

Professor R. Katie Morris MBChB, PhD, MRCOG, Professor of Obstetrics and Maternal Fetal Medicine
Director of Birmingham Clinical Trials Unit
Honorary Consultant Maternal Fetal Medicine, Birmingham Women’s and Children’s Hospital

Single-stranded suture threads could prevent pregnancy infection complications, finds C-STICH trial

Written by Louise Stanley on 26/10/2022. Posted in Clinical trials, Maternal health.

Women at risk of pregnancy loss who need a specialist surgical procedure are at a lower risk of infection if the procedure is carried out using a single-stranded suture thread, results from the C-STICH clinical trial found.

The trial was the largest of its type and is published in the Lancet. It involved more than 2,000 expectant mothers who needed a procedure called a cerclage, where a purse string suture is placed around the cervix (the neck of the womb) during pregnancy. Women were randomly allocated to have the surgical procedure performed using either a single-stranded thread or a braided thread.

Researchers tested whether there would be any difference in miscarriage or stillbirth, due to an increased risk of infection, from using a braided suture thread. The research, funded by the NIHR, demonstrated that single-stranded sutures could potentially improve outcomes for mothers at risk of preterm birth.

The team led by researchers from Birmingham Women’s and Children’s Hospitals (BWC) and the University of Birmingham – both founder-members of BHP – found that the mothers treated with single-stranded threads had no differences in pregnancy loss or preterm birth but reported fewer instances of infection and sepsis. This could have important implications for the health outcomes of mothers and babies who are treated with a cervical cerclage in their pregnancy.

Dr Vicky Hodgetts-Morton, NIHR Clinical Lecturer in Obstetrics at the University of Birmingham and Birmingham Women’s Hospital explained the implications of the trial results. Dr Hodgetts-Morton said:

“Preterm birth is a significant problem, complicating approximately one in ten pregnancies around the world. The consequences of preterm birth may be significant with some babies being born too early to survive, and those that survive are at increased risk of health complications. One cause for preterm birth is cervical insufficiency, occurring in 0.5% to 1% of pregnant women for which the placement of a vaginal cervical cerclage can be an effective treatment.

“Suture thread choice has the potential to improve how well a cerclage works in preventing miscarriage, stillbirth and preterm birth. Both single stranded and braided threads are commonly used to perform cerclages and our findings show no differences in pregnancy loss and preterm birth. The C-STICH trial results did show an increased risk of infections in labour and around the time of delivery with braided threads and this supported our hypothesis that a single stranded thread could reduce the risk of infection developing during the pregnancy.”

Mr Philip Toozs-Hobson, Chief Investigator of the C-STICH project and Consultant Gynaecologist at the Birmingham Women’s Hospital said:

“We are extremely grateful to all the women who trusted us by taking part in the study and also the dedication of the research teams at of the 72 maternity units who made the trial happen. Our aim, as ever, is to improve women’s experience in pregnancy through safer childbirth and to help the NHS achieve their target of reducing both pre-term birth and cerebral palsy. This work has added to our understanding relating to infection and sepsis.”

The study also highlighted that while single stranded suture threads led to better outcomes around infection, clinicians mentioned that such suture threads were subjectively more difficult to remove and more often required surgery to help remove under a general anaesthetic.

First Midlands research collaboration to focus on patient safety

Written by Louise Stanley on 14/10/2022. Posted in Early diagnosis and detection, Health inequalities, Maternal health.

Expectant mums and anyone needing emergency treatment will both benefit from funding for new research to improve patient safety and reduce the risk of harm.

BHP founder-members the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust will be establishing the first research collaboration focused on patient safety based in the Midlands, thanks to new funding from the National Institute for Health and Care Research. The announcement made today by the Department for Health and Social Care will see £3.4m invested in world-leading research that supports patient safety in maternal and acute care settings.

The newly announced NIHR Midlands Patient Safety Research Collaboration (PSRC) will bring together NHS trusts, universities, and private business to evaluate how digital tools can support clinical decision making and reduce risks for patients.

Professor Alice Turner is a Professor of Respiratory Medicine in the Institute for Applied Health Research at the University of Birmingham, Honorary Consultant Respiratory Physician at University Hospitals Birmingham, and Co-Director of the NIHR Midlands Patient Safety Research Collaboration along with Professor Richard Lilford, Professor of Public Health at the University of Birmingham.

She commented: “Patient safety is at the forefront of every clinician’s mind and runs at the heart of the whole healthcare system. The power of new technology available to us means that we can address one of the ongoing areas of risk for patients, which is effective communication and clinical decision making.

“Thanks to the new funding from NIHR and with the support of partners, the new collaboration will be looking at how digital tools can make a real difference to reduce risks and support patient safety in the key areas of acute medicine and maternal health.”

Acute Care

Patients requiring emergency medical care in acute services will benefit as new digital decision-making tools could improve prescribing and personalised management.

Thanks to the funding, the NIHR Midlands PSRC will trial digital clinical decision support tools which will provide smoother flow of information between healthcare professionals in acute care. Working with acute care hospitals, primary care providers and the West Midlands Ambulance Service, the researchers will review how the digital tools can reduce risks of patient harm at key points in acute care management.

Professor Elizabeth Sapey, Director of the Institute of Inflammation and Ageing at the University of Birmingham and an Honorary Respiratory Consultant at the University Hospitals Birmingham said: “The vision is that every healthcare professional involved in a patients journey in acute care has access to the same information, the same decision-making support, and is able to both spot and flag any point where patients might be at increased risk of harm.

“We know that a disproportionate number of medical errors happen in acute services, and around half of patients experience a clinical error in what can be a complex journey. As acute care becomes more heavily relied on, it is critical that we use technology available to us to ensure that our patients are kept safe and risk is managed.”

Mothers and babies will benefit from the new research collaboration to look at how digital tools can support antenatal decision making.

The collaboration will examine the effectiveness of clinical decision-making tools to recognise risks among expectant mothers, particularly among marginalised groups who experience worse outcomes and quality of care compared to the general population.

Professor Shakila Thangaratinam, Co-Director of WHO Collaborating Centre for Global Women’s Health at the University of Birmingham and Consultant Obstetrician at the Birmingham Women’s Hospital said: “Maternal and perinatal mortality reports in the UK have highlighted that there are real issues when it comes to identifying and responding to risk. One of the key priorities is identifying early in pregnancy those mothers who need the extra support and care, thereby ensuring that women receive individualised care during pregnancy.

“With this new funding from the NIHR, we can evaluate how digital tools can help clinicians ensure that no mum falls ‘through the net’ in identifying risk, and ensure every family receives the right level of support.”

Partners involved in the NIHR Midlands Patient Safety Research Collaboration

University Hospitals Birmingham NHS Foundation Trust (BHP)
University of Birmingham (BHP)
Birmingham Women’s and Children’s NHS Foundation Trust (BHP)
Health Innovation West Midlands (BHP)
NHS Birmingham and Solihull Integrated Care Board
University of Warwick
University of Aberdeen
Clevermed Limited
West Midlands Ambulance Service University NHS Foundation Trust
Shrewsbury and Telford Hospital NHS Trust

Drugs to delay preterm birth are safe for global reduction in neonatal death

Written by Louise Stanley on 16/08/2022. Posted in Health inequalities, Maternal health.

Women around the world should be able to access the best drug treatments that help to delay preterm births and improve outcomes for newborns, suggests new research.

Researchers from BHP founder-member the University of Birmingham worked with colleagues from the World Health Organization to review 122 randomised trials – published between 1966 and 2021, involving 13,697 women and conducted in 39 countries including high, middle and low-income states. The study, published in Cochrane Reviews, has allowed researchers to create a league table of drugs that delay birth, called tocolytics, based on their effectiveness and side effects.

Women benefitted from all preterm delay treatments included in the meta-analysis of studies, although the research team noted that the effectiveness of different drugs was less clear in some of the studies. The team also looked at the side effects of different drugs and combinations, including the likelihood of having to stop treatment.

The team have bought together the evidence on the benefits as well as the harms of these treatments (compared to no treatment or placebo), to arm clinicians and policy makers around with world with the information to decide upon the best treatment for the women in their care in their specific setting.

Dr Amie Wilson, Research Fellow Global Maternal Health at the University of Birmingham said: “The findings show that the benefits of these drugs outweigh any risks associated with unwanted side effects. These treatments are leading to a significant reduction in the number of deadly preterm births, and we now need to further understand the effectiveness of tocolytics for specific groups depending on pregnancy length.

“Our previous research has led to the improvement of guidelines for use of tocolysis drug use to delay preterm birth in the UK. Knowing that this paper helped to inform the forthcoming recommendations of the World Health Organization on the use of tocolytics, we hope that many more women around the globe will have access to these drugs, and have healthier births.”

Dr Victoria Hodgetts Morton, NIHR Clinical Lecturer in Obstetrics at the University of Birmingham and co-author of the paper said: “Preterm birth is the most common reason why a newborn baby may die, and the leading cause of death in children under five years of age.

“Tocolytics aim to delay preterm birth and allow time for the women to receive medicines that can help with baby’s breathing and feeding if born preterm, and medicines that lower the chance of cerebral palsy of the infant. Crucially, a short delay in preterm birth can enable women to reach specialist care.”

Professor Peter Brocklehurst responds to the Women’s Health Strategy

Written by Louise Stanley on 04/08/2022. Posted in Birmingham Health Partners, Maternal health.

The Chair of the Birmingham Health Partners Commission which led the Healthy Mum, Healthy Baby, Healthy Future report has welcomed the first ever Women’s Health Strategy for England to tackle the gender health gap.

The commission set out a raft of recommendations for the UK to lead the development of safe, effective and accessible medicines for use in pregnancy. The key ambitions in the Women’s Health Strategy which are aligned to the recommendations from the Healthy Mum, Healthy Baby, Healthy Future report include:

- - Boosting participation of pregnant women in clinical research, particularly clinical trials, key components to improving maternal health outcomes for women and their babies
  - A greater use of routine health data to improve outcomes for pregnant women
  - Improving the safety of medicines in pregnancy to ensure women have access to high quality and updated information about medicines that they may need to take during pregnancy

Commenting on the Women’s Health Strategy, Professor Peter Brocklehurst, Professor of Women’s Health and Director of Research and Development for the Birmingham Clinical Trials Unit (BCTU), said:

“I am really pleased to see that women’s health is being given the prominence it needs and I find the plans outlined in the Women’s Health Strategy encouraging. It is vital that women are treated as equal partners in the delivery of their care and that they have the option to be included in research and clinical trials that affect them. Over 50% of respondents to the initial call for evidence felt that pregnancy should be included in the strategy, providing a clear message that healthy pregnancies are a health priority for women, their families and society.

“The focus on the importance of research to continue to improve health is also very encouraging, however, there is little mention of the research needed to ensure that new therapies, particularly safe and effective medicines, are developed for many of the women’s health problems highlighted in the report. Investment in discovery science and the need for close collaboration with other groups, particularly the pharmaceutical industry, is essential if we are to continue to improve health outcomes for women. I look forward to building on these plans with colleagues in Government and across sectors to reduce the gender health gap, place women’s voices at the heart of research, increase participation in research and ultimately improve maternal health outcomes for women and future generations.”

Baroness Thornton – the Shadow Women and Equalities Minister, recently spoke about the Healthy Mum, Healthy Baby, Healthy Future report during her statement to the House of Lords on the Women’s Health Strategy. The full debate can be watched here. (Baroness Thornton’s speech starts at 16:07:05 and is answered by Baroness Penn at 16:23:45, she ends her point on the report at 16:25:15).