Updated February 2014

photo of testubes with heading: Our research: recent achievements

Recent research achievements

Recent achievements in miscarriage and stillbirth research

We've set up the UK's first placenta clinic

The placenta is the baby's life-support machine so when it goes wrong all sorts of problems can occur, including miscarriage. In 2009 Tommy's opened the UK’s first clinic to focus on the placenta to improve monitoring of women whose pregnancies are affected by fetal growth restriction. This has the dual benefit of ensuring that the women get the best standard of care and giving our scientists a chance to study placental function. The Manchester Placenta Clinic has now finished its first five-year cycle and is achieving approximately 1000 patient episodes per year. The Clinic has recently also seen the integration of Rainbow Clinic, which focuses on the care of women with a previous stillbirth. Sadly as fetal growth restriction is strongly associated with stillbirth, many of the patients will have had a stillbirth previously. This new Clinic formalises the care of these women and provides additional services to them.

We’ve shown that Viagra is a promising new treatment for fetal growth restriction

Abnormal growth of the baby in the womb (called fetal growth restriction) can cause stillbirth or, if detected, leave parents and obstetricians with the only option of delivering a baby very prematurely, when it may die anyway or be left with lifelong handicap. The Tommy’s team in Manchester has recently worked with a group of obstetricians in Canada to conduct a small human trial to determine whether Viagra might improve the growth of babies severely affected by fetal growth restriction. We found that it does indeed improve growth, and without causing any harm. These exciting results have led directly to the setting up of a large multicentre clinical trial in the UK, in which Tommy’s scientists are playing a leading role. 

We’ve shown that elective induction of labour at term in older women reduces the risk of stillbirth

By analysing Scottish birth records for more than 1 million women from 1981 to 2007, we were able to show that elective induction of labour from 37 weeks of gestation onwards reduces perinatal mortality. We also showed that it does not increase the risk of needing a caesarean section delivery. Our published results have been widely cited and, importantly, they stimulated new guidelines from the Royal College of Obstetricians and Gynaecologists that women at high risk (older women) should be offered routine induction of labour from 39 weeks of gestation. Implementation of this recommendation is likely to prevent the stillbirths of 17 babies per year in the UK.

We’ve developed MRI techniques for studying the placenta

One of the main causes of stillbirth is fetal growth restriction due to problems with placental blood flow. We have successfully developed new magnetic resonance imaging (MRI) techniques that can detect abnormalities in the placenta. We have also identified tissue fibrin as a possible marker for the condition. We hope that MRI, which is safe to use during pregnancy, could soon be used as a tool for diagnosing or predicting fetal growth restriction.

We’ve identified factors that affect placental blood flow

In pregnancy, blood vessels to the uterus get bigger to increase blood flow to the baby. If this does not occur, risks include miscarriage, pre-eclampsia or having a baby too small or too early. We have identified factors – released by placental cells called trophoblast cells – that cause this and are now looking at ways to improve blood vessel widening.

We’ve pioneered guidelines on fetal movements

Our research has shown that reduced fetal movement might be a reliable predictor of pregnancy complications. Previous practice in this area was found to be chaotic and non-evidence-based so our research has helped create a much more robust guideline for pregnant women to become aware of their own baby's activity levels.

We’ve improved our understanding of calcium transport via the placenta

Growth-restricted babies are far more likely to be stillborn or have other problems. One way this can occur is if the baby doesn’t get enough calcium, a process that is controlled by the placenta. We have investigated the genetic background to calcium transport in a mouse model and have been able to show that, when there is a specific genetic deficiency, the calcium concentration in the fetus’s blood is lower than in the mother’s, when it should be the other way around. The mouse models have proven to be excellent models with which to assess placental calcium transport in human fetal growth restriction. They will allow us to develop and test therapeutic strategies for growth-restricted babies in the future.

We’ve shown that homocysteine reduces the placental supply of amino acids to the fetus

Evidence suggests a connection between the amino acid homocysteine and a range of pregnancy complications, including recurrent miscarriage, pre-eclampsia, spina bifida, neural tube, heart and limb defects, fetal growth restriction and stillbirth. We have shown that homocysteine can decrease the placental transport of other essential amino acids between mother and baby. We have also found that nutritional deficiencies in folate and vitamin B12 can lead to a build-up of homocysteine within cells.

We’ve shown that estrogen can improve placental blood flow

We have been studying the mechanisms for regulating blood flow to and within the placenta, focusing particularly on the role of estrogen and insulin-like growth factor (IGF-1). We have shown that the blood vessels in the placenta and womb relax in response to estrogen, allowing improved blood flow. With further research, estrogen may become a possible treatment for pregnancies where the baby isn't growing properly.

We’ve shown that MRI can be used non-invasively to detect placental insufficiency and fetal hypoxia

Currently, we are not able to directly measure placental function and fetal health within the womb. However, we have recently demonstrated for the first time that MRI can be used non-invasively to measure placental metabolism. This has real potential to reduce stillbirths by identifying those babies at greatest risk of coming to harm within the womb and by enabling doctors to time their delivery appropriately.

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Recent achievements in premature birth research

We’ve achieved an NHS Innovation Challenge Award for reducing premature birth

Our unique Preterm Surveillance London clinic based at St Thomas’ Hospital  and part of the Guy’s and St Thomas’ NHS Foundation Trust has successfully reduced the number of premature births in South East London from 9.2 percent to 7.8 percent.

The clinic is led by Professor Andrew Shennan, who is also Professor of Obstetrics at King’s College London. The clinic focuses on screening for, treating and preventing pre-eclampsia and premature birth.  The prize was awarded in the ‘Better Management of Pregnancy’ category and under the challenge of ‘Innovation’ – which rewards innovative healthcare practices and ideas that have demonstrated a positive impact in the local context where they have been implemented, but which have not yet received wider recognition.  

We’ve moved a step closer to a predictive test

Tommy’s scientists have shown that fetal fibronectin, a special protein enabling the membranes around the baby to stick to the walls of the womb, should only appear at around 22 weeks and again at the end of pregnancy. If it appears between these dates it indicates that an early labour is imminent, which means that it is an excellent predictor for preterm birth. Our initial trial was highly encouraging and we are now evaluating a more accurate quantitative machine for analysing fetal fibronectin (the EQUIPP study). If this more accurate test proves to be cost-effective, there will be much wider use of this predictive test for preterm labour. This will help to prevent hospital admissions and unnecessary interventions for women at low risk, thereby reassuring them and saving precious healthcare resources.

We’ve developed a simple saliva test for predicting preterm labour

We have filed a patent on a new saliva test for prediction of early preterm labour. If validated in an ongoing study, this simple test could be used to predict which women may go into labour very early, allowing for greater surveillance and early intervention. This may be particularly valuable in identifying women who would benefit from progesterone supplementation.

We’ve shown that omega-3 fatty acids can reduce inflammation in fetal membranes which is associated with preterm labour

We’ve shown that omega-3 fatty acids, which are found in dietary fish oil supplements, have a direct anti-inflammatory effect on fetal membranes. This may be one mechanism through which fish oil supplements can prolong gestation. We have now extended this work to look at other anti-inflammatory/antimicrobial peptides present in the lower genital tract. 

We’ve found a potential treatment to prevent brain injury in premature babies

There is increasing evidence of a link between inflammation in the womb and preterm labour. In our studies of the mechanisms responsible for inflammation‐induced preterm labour in a mouse model, we have identified a previously unrecognised role for complement activation in several pregnancy complications, including miscarriage, fetal growth restriction and pre-eclampsia. (The ‘complement’ system consists of over 25 proteins that circulate in the blood and it is part of the body’s immune system.) We have recently also demonstrated that complement activation plays a crucial role in changes in the cervix during preterm labour. This work has suggested that complement inhibitors and/or statins might be an effective treatment to prevent preterm labour and neonatal brain injury.

We’ve improved our understanding of inflammatory causes of preterm birth

We have investigated whether the spread of infection from the vagina to the womb plays a role in preterm labour. We also looked at how useful two commonly used treatments (progesterone or a cervical stitch) were at suppressing inflammation and preventing early delivery of the baby. Our results have given us important clues as to the mechanism of early birth and may help us develop a test to identify women at risk earlier in pregnancy. We are now looking forward to investigating whether this test also helps women in their first pregnancy. This information will help doctors determine when to treat women, and with what.

We’ve found a possible way to predict preterm labour early in pregnancy

One potential cause of preterm labour is infection that spreads from the vagina into the womb, and some women seem to be less able to mount an appropriate immune response and produce natural antimicrobial substances (nature's antibiotics). Our work has identified elafin, a natural antimicrobial peptide, as a potentially useful indicator of women most at risk of preterm birth. An initial patent application has been submitted and commercial partnerships are being explored to pursue potential development of a bedside test using elafin as an ‘early pregnancy’ biomarker of preterm birth. Such a test early in pregnancy would add to the current use of fetal fibronectin for prediction of preterm birth at gestations late in pregnancy.

We’ve shown that vitamin D enhances the body’s natural antimicrobial defences

We have recently demonstrated that vitamin D supplementation enhances natural antimicrobial peptide production and this could help to prevent infection in the vagina from spreading to the womb and triggering preterm labour. We are thus now studying vitamin supplementation in women at high risk of preterm labour.

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Pre-eclampsia

We’ve developed a cheap yet effective device to measure blood pressure and detect pre-eclampsia in low-income countries

Our research group has developed a blood pressure device that can be manufactured for less than $20 and that uses a manual pump to inflate the cuff. This makes it ideal for use in low-income countries and we have successfully piloted its clinical use in a feasibility study in sub-Saharan Africa. The introduction of the device into peripheral clinics increases referrals from the community to hospital facilities for suspected pre- eclampsia.

We’ve demonstrated links between poor placental function and pre-eclampsia

Normally cells in the placenta die and replenish at an even rate. However, in women with pre-eclampsia, these cells often die at a faster rate than they can be replaced. Our research has found several reasons for this. It can be caused by an imbalance in two proteins, by low oxygen and oxidative stress, or by the overproduction of a protein called TRAIL. We have also shown that treatment with a commonly used medicine like heparin can reduce these effects.

We’ve discovered that the hormone kisspeptin inhibits placental blood vessel growth

In a series of experiments in the test tube, we showed that the hormone kisspeptin influences the way blood vessels develop. We then tested this in the placenta and showed that kisspeptin reduces the amount of new blood vessel formation. This exciting finding may be important for diseases in pregnancy which result from poor placental development, such as pre-eclampsia and low birthweight.

We've identified two proteins that could identify women at risk of pre-eclampsia

There is currently no screening test which can effectively predict pre-eclampsia. However, using a new mass spectrometry technique that we developed, we have identified two pregnancy-specific glycoproteins (PSG 5 and PSG 9) that are significantly elevated in women who subsequently develop pre-eclampsia. In combination with measurements of placental growth factor (PlGF) and clinical risk factors, these proteins could become an important component of a predictive test for pre-eclampsia.

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General pregnancy health

We’ve confirmed that maternal obesity has long-term health risks for the child

In a study of people born in the Aberdeen area since the 1950s, we found that maternal obesity was associated with a 35% increase in premature death in the adult offspring, and a 29% increase in the risk of hospital admission for a cardiovascular event. The results were published in the BMJ in August 2013 and attracted considerable media interest. At current rates, maternal obesity will be associated with the premature deaths (before age 50) of 7,000 people per year in the UK. 

We’ve shown that maternal obesity has consequences for the second-generation offspring

We explored the effects of maternal diet-induced obesity on the offspring in a mouse model. Surprisingly, there were few effects on the first-generation offspring. However, we found clear evidence of fetal growth restriction and persistent metabolic changes in the second-generation offspring. Effects on birthweight, insulin levels and gene expression in the liver were transmitted through both maternal and paternal lines. This suggests that the consequences of the current dietary obesity epidemic may also have an impact on the descendants of obese individuals, even when the first generation appears to be largely unaffected. 

We’ve confirmed that obesity reduces fertility

We have found that maternal obesity can depress fertility and alter cellular metabolism in eggs and early embryos. We have also established that these very early changes persist to the later fetal and infant stages. This research is highly relevant to the increase in obesity of women of childbearing age, to assisted reproduction techniques (ART), and to potential embryonic stem cell based regenerative therapies.

We’ve set up a clinic for obese pregnant women

Nearly half the women of childbearing age in the UK are overweight or obese. We know obesity makes a whole host of pregnancy problems more likely but we don't as yet know why. In 2009, Tommy's established the Edinburgh Antenatal Metabolic Clinic at our research centre which is now providing about 200 women a year with enhanced care throughout their pregnancy and also providing our scientists with valuable data to study the link between obesity and poor pregnancy outcome.

We’ve demonstrated that measuring arterial stiffness in obese pregnant women can identify those at risk of blood pressure complications

We have recently demonstrated that using the Vicorder device is a valid and reliable method for routine measurement of arterial blood vessel stiffness in obese pregnant women. Given that arterial stiffness increases before blood pressure does, this technique could be a useful screening tool to identify mothers who have an increased risk of developing blood pressure complications in later pregnancy.

We’ve confirmed that a mother’s diet during pregnancy can have long-term effects on her child

A group of men and women born in the late 1960s in Motherwell whose mothers’ food intakes in pregnancy were recorded took part in this study. We examined the effects of an ‘Atkins-type’ high-protein, low-carbohydrate diet during pregnancy on how regulation of key genes in the offspring is altered. Our study was the first to show that regulation of a number of genes which may be important in increasing the risk of diseases such as adult obesity and high blood pressure was related to the size of the baby at birth and, importantly, was altered by the diet eaten by the mother in pregnancy. This highlights the importance of the early life environment for future health.

We’ve found that domestic violence and maternal depression are associated with future behavioural problems in the child

In a study of 13,617 children and mother pairs followed to 42 months of age, we found that most women who experience antenatal violence also experience postnatal violence. Domestic violence experienced in pregnancy is associated with depression during pregnancy and postnatal depression. Furthermore, domestic violence and maternal depression are associated with future behavioural problems in the child. A review of the literature also revealed that that there is a strong association between domestic violence and mental health, though this is frequently not detected by clinicians in mental healthcare settings.

We’ve found that teenage mothers are not at risk of having small babies if they themselves are still growing

The UK has the highest rate of teenage pregnancy in Western Europe. Younger women are at increased risk of pregnancy complications, particularly small for gestational age (SGA) babies. We have found that placentas in teenagers have a reduced ability to transfer amino acids compared to placentas from adult pregnancies. However, in our recent study (About Teenage Eating Study; ATE) of 500 pregnant teenagers in Manchester and London we have also found that placentas from teenagers who are themselves still growing have a higher ability to transport amino acids than those from non-growing teenagers. This is consistent with growing teenagers delivering higher birthweight babies.

We’ve improved our understanding of the link between gestational diabetes and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver condition in the Western world and It is known to be associated with type 2 diabetes; however, it is not known whether NAFLD predates the development of type 2 diabetes. In a study of 223 women, we found that those women who had had previous gestational diabetes were at significantly higher risk of developing NAFLD.

We’ve developed liver function tests for obese pregnant women that can identify those most at risk of gestational diabetes

We have found that obese women display a unique pattern of liver function tests as their pregnancy progresses, compared with women with normal weight at their booking visit. In particular, the liver enzyme GGT was found to be an independent risk factor for subsequent gestational diabetes in our high-risk pregnant women, raising potential clinical interest in this test as a predictor of subsequent gestational diabetes at 24–28 weeks.

We’ve developed a successful device (Desperate Debra) for training doctors to manage complicated caesarean section deliveries

We have successfully developed a medical simulator, known as Desperate Debra, for training doctors to carry out caesarean section deliveries when the baby’s head is impacted in the mother’s pelvis. The device has already gone into commercial production and models have been sold in the UK and overseas. Desperate Debra will be an intrinsic part of training doctors to manage this obstetric complication.

We’ve quantified the clinical and short-term NHS costs of maternal obesity for maternity services in Scotland

Half of all Scottish women of reproductive age are overweight or obese and maternal obesity has significant implications for the health of mothers and their babies. Using the Scottish maternity database, we analysed the effect of maternal obesity on clinical outcomes in Scotland and also estimated the associated costs to the NHS. Women who are overweight are more likely to have maternal complications, require additional hospital care and incur higher medical costs for the NHS. The increased costs to the NHS per pregnancy for antenatal admissions alone for women who were overweight, obese or severely obese were £60, £202 and £351, respectively. The results were published in January 2014 and have gained considerable press interest. Locally, strategies and guidelines should be developed to minimise risk and optimise perinatal outcome. Nationally, the impact of maternal obesity should be considered when redesigning services. We are also using the results of this study to improve the care we provide for the women who attend the Edinburgh Antenatal Metabolic Clinic.

We’ve shown that the differences in insulin sensitivity between obese and lean pregnant women are greatest in early pregnancy

Our AMPOP metabolic study measured sugar and fat metabolism in lean and obese women during pregnancy, and in lean and obese non-pregnant women. We found that differences in insulin sensitivity between obese and lean pregnant women are greatest in early pregnancy and that the maternal liver is spared from the adverse effects of maternal obesity. However, the resulting increased circulating lipids could have adverse effects on both the baby and the mother’s health, and interventions to prevent these effects of obesity should be delivered as early as possible in the pregnancy. These results provide further support for the rationale for the EMPOWaR study, in which we will determine whether improving insulin sensitivity in obese pregnant women improves outcomes.

We’ve shown that yoga can reduce maternal anxiety during pregnancy

Previous Tommy’s research has shown conclusively that maternal anxiety can have an adverse effect on pregnancy outcome. Anxiety and fear of delivery usually increase as pregnancy progresses. We have now found that an eight-week course of yoga significantly reduces women’s anxiety scores as well as their levels of the stress hormone cortisol.

We’re taking the lead in developing resources for women experiencing distress and mental health problems in pregnancy

It is known that stress resulting from living conditions, life events and related pressures can adversely affect mother and baby during pregnancy. A tool (the ‘Whooley questions’) which was recently introduced into routine clinical practice for detecting women at risk of depression was found to miss many possible cases. A number of factors which influence women’s willingness to disclose stress were uncovered. This research was the first study to validate the use of the Whooley questions in UK clinical practice. Zoe Darwin won the Society of Reproductive and Infant Psychology (SRIP) Annual Doctoral Thesis Award 2013 for this work. She was invited to contribute to a workshop on Measuring Psychological Health in the Perinatal Period and this workshop hsd led to a recently published national consensus statement. Zoe has become a member of the Tommy's Expert panel on Maternal Mental Health resources, and is working with Beckie Lang, the Health Campaigns Manager at Tommy's, to develop resources for women experiencing distress and mental health problems in pregnancy. 

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Achievements in miscarriage and stillbirth

Achievements in premature birth

Pre-eclampsia

General pregnancy health



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