Last updated: December 2012
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. So far, 2118 examinations in over 500 pregnant women have been performed, with detection rates for fetal growth restriction of 75%.
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 a larger study, which has almost finished recruitment, 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 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 tested and developed improved blood pressure devices
We have recently completed the testing and development of a range of automated and manual blood pressure devices. These include devices suitable for use in pregnancy and pre-eclampsia, a low-cost but accurate ‘chemist’ device that could result in major savings if rolled out across the NHS, and a solar-powered device for the World Health Organization. Tommy’s Professor Andy Shennan has also been involved in writing new international standards for validation protocols, and has advised the EU on legislation regarding replacement of mercury in these devices.
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 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 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 pregnant women are often unaware of the risks of obesity to them and their babies
In a study of women’s perceptions of the risks of their obesity for their general health and for their pregnancy, we found that all of the women in the study claimed that before they were pregnant they had been largely unaware of the risks that obesity posed to them and their babies. The majority felt that inadequate reference had been made to obesity and the associated risks both before and during pregnancy. In some cases, this had caused concern or confusion.
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 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. We found that maternal obesity is associated with increased risk of hypertension, diabetes, other maternal diseases, induction of labour, caesarean section, premature birth, macrosomia, stillbirth and neonatal admission. Being obese or underweight were both associated with increased maternal inpatient costs. Maternal outpatient costs were significantly higher in obese women, and neonatal costs were significantly higher in both underweight and obese women.The additional maternal admission cost associated with being overweight was £214, with obesity £550, and with with morbid obesity £1,035. 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.
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