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Last updated: December 2012

Pregnancy health

In addition to our core work on miscarriage, stillbirth, preterm birth and pre-eclampsia, Tommy’s also funds research projects aimed at improving pregnancy outcomes in groups who tend to be at higher risk. This includes younger mothers and overweight or obese mothers.

Indeed, our centre in Edinburgh is dedicated to analysing the relationship between pregnancy outcome and obesity. This is extremely important if we’re to improve pregnancy statistics in the UK as almost half the women of childbearing age are now obese or overweight.
As part of the UPBEAT trial, our London centre has developed a dietary and physical activity intervention for obese pregnant women based on behavioural theory. The success of the pilot study has meant that funding has been obtained for a multicentre randomised controlled trial, in which psychological aspects, service delivery and health economic issues will also be addressed. This project could make a significant difference to the health of obese women during pregnancy.
We have also been running ten-week community exercise classes for obese pregnant women, which they can attend with their children if they choose to. Alongside the exercise classes, we are running a multi-faceted lifestyle programme that includes physical activity, healthy eating, motivational techniques, personal care during pregnancy and social networking.
Tommy’s London centre is involved in several parts of the large multinational EU study known as EarlyNutrition, which is addressing the long-term effects of early nutrition on later life. Professor Poston is leading a number of intervention studies in pregnant women or in infants. These will assess the impact of an intervention comprising a low glycaemic index diet and increased physical activity on adiposity in children of obese pregnant women taking part in the UPBEAT study. The aim is to develop successful strategies for prevention of childhood obesity and related cardiovascular and metabolic disorders by influencing early-life dietary and/or physical activity behaviours.
We are investigating why some babies don't grow properly in the womb and how conditions experienced during pregnancy might `programme' the offspring to have greater risk of heart disease, obesity and diabetes later in life. It is generally known that genetic mutations can cause certain diseases but in recent years it has become clear that environmental factors might also increase the risk of disease in the offspring by changing the way that genes work (‘epigenetic’ changes), without actually causing mutations. We are studying whether maternal obesity or an unbalanced diet are associated with persistent epigenetic modifications in the offspring. In a separate study, we are investigating whether a safe dietary supplement can prevent cardiovascular disease arising from nutritional imbalance during fetal development.
Our Manchester centre continues to have a major focus on the placenta and why this vital organ sometimes stops working properly in pregnancy – to the detriment of the health of both mother and baby. Amongst our new findings is the observation that obesity alters the way that the placenta can transfer nutrients to the baby, increasing the risk of bad outcomes for the pregnancy. This information will enable us to work out ways to combat these problems in the placenta.
Stress resulting from living conditions, life events and related pressures can adversely affect mother and baby during pregnancy. However, there are no reliable tools for detecting a broad range of stress factors and our centre in Manchester has thus conducted a pilot study into how antenatal care services can best identify vulnerable women. This research has led to a larger definitive study, which is now under way.
Smoking in pregnancy is one of the most important risk factors for low birthweight, very preterm birth and perinatal death. Women with mental health problems can find it particularly difficult to give up the habit and our London centre is developing smoking cessation interventions specifically for these women.
More than a quarter of babies born in the UK are delivered by caesarean section and if the baby’s head is very far down in the pelvis, a vacuum is created between the baby’s head and the womb, making it very difficult for the surgeon to remove the baby. Tommy’s scientists are working with the inventor of a device called the Tydeman Tube that has the potential to be the first completely safe way to release this vacuum. This work has also led to development of a ‘dummy’ for the purposes of training doctors to perform difficult deliveries.

Individual research projects

Investigating outcomes of pregnancies associated with severe obesity: the Edinburgh Antenatal Metabolic Clinic

Investigators: Professor Jane Norman, Dr Fiona Denison, Dr Rebecca Reynolds, Dr Shareen Forbes, Dr Mandy Drake, Graham Harold, Yvonne Greig

Funding: Tommy’s funds the entirety of this study

Timescale: 2008 onwards

Summary: Recent studies estimate that more than one in five pregnant women are obese. These mothers are at increased risk of developing complications during pregnancy but obesity also poses long-term health risks for the baby. Little is known about the physiological and hormonal changes that occur in pregnancies associated with severe obesity and how these impact on offspring development and obesity and metabolic risk. The best weight-management advice for severely obese women for optimal maternal and offspring health is not known. To address these questions, we have established the Edinburgh Antenatal Metabolic Clinic, which provides multidisciplinary antenatal care, including diet and lifestyle advice, to very severely obese pregnant women. In parallel, we are undertaking a detailed study of the women who attend the clinic and their offspring to characterise weight gain and change in body composition in the mothers and how this impacts on their children.

Progress report: The clinic has been up and running since August 2008 and over 300 women have now attended the clinic for their antenatal care. We also encourage the women to return with their babies for postnatal follow-up visits, which enables us to implement a weight management strategy and reinforce healthy lifestyle advice so that we can optimise maternal health prior to any subsequent pregnancy. We have now recruited 259 obese women and 111 lean women into the research study, and comparison with the control group will aid development of guidelines for women for healthy weight management in pregnancy. Children will be followed long-term to assess growth and the development of obesity and any metabolic problems. Biochemical parameters will be correlated with maternal and baby outcomes including weight gain, birthweight and pregnancy complications such as pregnancy-induced hypertension.

The energy balance in pregnancy study

Investigators: Dr Rebecca Reynolds, Yvonne Greig, Professor Jane Norman

Funding: Tommy’s fund some of the consumables and laboratory analyses in this study

Timescale: 2009 onwards

Summary: Pregnancy is associated with increased energy requirements for the mother to provide nutrition for the developing baby. Little is known about the energy changes that occur in pregnancies associated with severe obesity and how the mother adapts her metabolism to ensure her baby grows well. The aim of this project is to carry out a detailed study characterising energy balance in very severely obese pregnant women compared to normal-weight pregnant women. Furthering our understanding of diet and exercise in women with severe obesity is necessary in order for us to design suitable interventions to promote healthy eating and activity and to optimise pregnancy weight gain and birthweight.

Progress report: In women recruited from the Edinburgh Antenatal Metabolic Clinic, we found that obese pregnant women tended to under-report their total energy intake and over-report their physical activity. Self-reported methods were thus less reliable in assessment of diet and physical activity in severely obese compared to lean pregnant women. In a pilot study, we carried out measurements using ‘doubly labeled water’, which is an accurate and objective measurement of total energy expenditure. This method involves asking women to drink some ‘labeled’ water and then collecting urine samples on four occasions over the following fortnight. This pilot study showed that, importantly, this method was acceptable for our pregnant women. We have established a collaboration with international leaders in energy expenditure and we are now recruiting more women into this study. We anticipate that data from this project will enable us to develop a trimester‐specific gestational weight gain calculator for severely obese pregnant women.

The Study of Cortisol and Overweight in Pregnancy (SCOOP)

Investigators: Dr Rebecca Reynolds, Graham Harold, Yvonne Greig, James O’Reilly, Professor Jane Norman

Funding: Tommy’s funds Ms Greig and Mr Harold and some of the consumables in this study.

Timescale: 2008–2013

Summary: Over-exposure of the developing baby to steroid stress hormones results in low birthweight, as well as increased risk of raised blood pressure, diabetes and cardiovascular disease in later life. It is known that steroid stress hormone levels rise in normal pregnancy. They are also altered in obesity but there are no studies examining how steroid stress hormone levels change in pregnancies associated with obesity. This project is studying women during and after pregnancy to see whether increased production of steroid stress hormones during pregnancy influences offspring birth size. This will help us to understand how a predisposition to cardiovascular disease can be passed from mother to child.

Progress report: Obese and lean pregnant women are being recruited from the Edinburgh Antenatal Metabolic Clinic. Blood and saliva samples are currently being analysed for cortisol levels. The women also complete questionnaires to assess stress, anxiety and depressive symptoms during pregnancy. Preliminary results show that both physiological and psychological stresses in maternal obesity have adverse impacts on birthweight and delivery gestation. We have also found that that lower circulating cortisol levels may be a mechanism contributing to higher birthweight in obese women. Screening and counselling for stress in pregnancy should be considered as a target to improve infant outcomes.

Do conditions in the womb ‘programme’ problems in later life?

Investigators: Rachel Dakin, Dr Vicky King, Brian Walker, Professor Jonathan Seckl, Dr Patrick Hadoke, Dr Mandy Drake, Professor Jane Norman

Funding: Tommy’s funds Dr King and some of the consumables for this study

Timescale: 2008–2012

Summary: Many studies have shown that the conditions experienced by the baby in the womb can increase the risk of diseases such as diabetes and high blood pressure in later life. In particular, studies have suggested that maternal malnutrition and/or exposure of the developing baby to excess stress hormones in the womb can have these effects. It is now becoming clear that maternal obesity can also increase the risk of obesity, diabetes and heart disease in the offspring. This study is investigating the mechanisms by which maternal obesity affects the long-term health of the offspring.

Progress report: In our mouse model we have found that maternal obesity is associated with a decrease in litter size and a reduction in offspring birthweight. Maternal obesity is not always associated with an increased risk of obesity and insulin resistance in the offspring although it does have some effects on gene expression and vascular function, particularly in male offspring.

Does metformin reduce excess birthweight in offspring of obese pregnant women? (the EMPOWaR study)

Investigators: Professor Jane Norman, Dr Fiona Denison, Dr Mandy Drake, Dr Shareen Forbes, Dr Rebecca Reynolds, Professor Brian Walker, Professor David Newby, Professor Gordon Murray, Professor Susan Wray, Dr Siobhan Quenby

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2010–2014

Summary: In this clinical trial known as EMPOWaR, we are evaluating whether giving obese pregnant women the drug metformin (an agent that restores maternal blood glucose and insulin resistance towards normal) reduces excess birthweight in their babies. Such excess birthweight is a surrogate marker of future life risk of obesity and metabolic syndrome. We will also use metformin to investigate how obesity causes adverse pregnancy outcomes, with a particular focus on insulin resistance. The design of the study is a double-blind randomised placebo-controlled trial. The target is to recruit 400 obese pregnant women, who will receive treatment either with metformin or a placebo.

Progress report: The EMPOWaR trial was initially scheduled to recruit women from Edinburgh and Liverpool only. However, we have had huge interest from other centres. We are currently recruiting from Edinburgh, Liverpool, Coventry, Sheffield and Nottingham. Over 170 women have so far been recruited to the study, which has received considerable press attention in the UK and overseas, including an interview with Professor Jane Norman on the Radio 4 ‘Today’ programme.

The UK Better Eating and Activity Trial (UPBEAT)

Investigators: Professor Lucilla Poston, Dr Helen Croker (UCL), Professor Andrew Shennan, Professor Jane Sandall, Professor Tom Sanders (KCL), Claire Singh, Paul Seed, Professor Jane Wardle (UCL), Professor Keith Godfrey (Southampton University), Professor Steve Robson (Newcastle University), Professor Christine Godfrey (University of York)

Timescale: 2008–2012

Summary: This major trial, known as UPBEAT or the UK Better Eating and Activity Trial, will develop a dietary and physical activity intervention to be used nationwide to improve pregnancy outcome for obese women. The intervention is based on improvement of blood sugar control by diet and physical activity, and is delivered in group sessions by a health trainer.

Progress report: The pilot study involving 117 women has been completed and the results analysed. The study showed a significant change in dietary intake in association with the intervention, notably a reduction in the dietary glycaemic load. The success of the pilot study has meant that funding has been obtained for a multi¬centre randomised controlled trial, in which psychological aspects, service delivery and health economic issues will also be addressed. The visit schedule and number of attendances required were modified to aid recruitment and retention of participants in the larger trial. The target number of women in this trial is 1,562 and so far 700 women have been recruited.

The EU EarlyNutrition study

Investigators: Professor Lucilla Poston, Dr Errol Richardson, Dr Paul Taylor, Professor Clive Coen, Emmanuel Domfeh, Claire Singh, Dr Susan Barr

Funding: Study taking place in a Tommy’s funded centre

Summary: EarlyNutrition is a large multinational EU study addressing the long-term effects of early nutrition on later life. The programme focuses on the developmental programming of obesity and associated disorders, with a view to understanding the underlying mechanisms and developing recommendations for optimised nutrition in pregnancy. Tommy’s London centre will be involved in several parts of the study. Professor Poston will be leading a number of intervention studies in pregnant women or in infants. These will assess the impact of an intervention comprising a low glycaemic index diet and increased physical activity on adiposity in children of obese pregnant women taking part in the UPBEAT study. The aim is to develop successful strategies for prevention of childhood obesity and related cardiovascular and metabolic disorders by influencing early-life dietary and/or physical activity behaviours.

Investigating maternal obesity and altered energy expenditure

Investigators: Xanthi Maragkoudaki, Dr Paul Taylor, Professor Lucilla Poston, Dr Sandra Einerhand, P Samuel (Tate & Lyle), Phillip Blower (King’s Division of Imaging Sciences)

Funding: Study taking place in a Tommy’s-funded centre

Summary: Obesity in pregnancy can increase the risk of a poor obstetric outcome, including pre-eclampsia, high blood pressure during pregnancy, and gestational diabetes. It is also now believed that maternal obesity can lead to similar problems later in life for the child born to this mother, such as obesity, high blood pressure and diabetes. We are investigating the mechanisms involved in producing these problems by analysing blood and blood products from a mouse that has similar maternal traits. To investigate energy intake and expenditure, we will use the non-invasive Comprehensive Laboratory Animal Monitoring System (CLAMS). Working with Tate & Lyle, who are developing ways of enhancing food with the necessary nutritional ingredients to maintain a balanced diet, we aim to provide these supplements to the maternal mouse to see whether this improves outcome for their offspring.

Progress report: The CLAMS methodology has now been optimised. Preliminary results in the offspring of obese mice have shown deficits in energy expenditure and respiratory exchange ratio at 5 months. Additional cohorts are currently being generated to confirm these preliminary findings.

Does altered placental nutrient transport link raised maternal BMI with poor fetal outcome?

Investigators: Andrea Ditchfield, Dr Sue Greenwood, Dr Mark Wareing, Dr Tracey Mills, Professor Colin Sibley

Funding: Tommy’s studentship to Ms Ditchfield

Timescale: 2008–2011

Summary: Currently, about 20% of women booking for prenatal care in the UK are obese. Being overweight while pregnant can have serious consequences for the growth and development of the baby. Mothers with a high body mass index (BMI) often have babies that are larger than normal. These overgrown babies are disadvantaged in both the short and long term. The placenta transfers the nutrients from the mother that are essential for the baby to develop normally and it is possible that placental transfer is compromised in obese mothers. To test this, we collected placentas after delivery and measured their ability to transfer nutrients. We found that the transfer of taurine, an amino acid particularly important for fetal growth and organ development, was lower in placentas of obese mothers compared to mothers of normal weight. This reduced transfer could lead to taurine deficiency in the baby which in turn would cause abnormal growth and development.

Community exercise classes to improve the wellbeing of obese pregnant women and the life chances of their children

Investigators: Professor Dame Tina Lavender, Dr Debbie Smith, Jacqui Clinton, Jane Brewin, Professor Colin Sibley

Funding: Study funded by Tommy’s through a grant from the previous Department for Children, Schools and Families (now known as the Department for Education)

Timescale: 2009–2012

Summary: There has been a rise in the number of women who are obese when pregnant. This results in pregnancy complications for the mother and baby. Children of obese women are also more likely to become obese. However, there are few services for women, particulary in deprived areas, to tackle this problem. We have been offering a ten-week exercise programme to support obese pregnant women in Oldham and Bolton, which they could attend with their children if they chose to. To assess whether this programme is acceptable to women and has any impact on their weight, we collected information using various methods, such as diaries, interviews, questionnaires and clinical records. We also introduced a food diary to collect data on obese pregnant women’s eating behaviours towards the start of their pregnancy and towards the end of their pregnancy.

Progress report: We recruited 259 women to take part in this feasibility study and the women attended the programme in groups of 20, with six programmes being run in each area. We also interviewed 30 health professionals in Greater Manchester who support women with a body mass index of 30 or more. Based on the findings of the feasibility study, the team made some amendments to the ten-week programme. A further 72 women were recruited and randomised to the intervention group or to standard care. This project has provided information about the needs of this target group and it has provided an expert model of good practice for obese women, i.e. an antenatal lifestyle course that appears to be suitable and acceptable to both women and health professionals. The qualitative study of health professionals has increased our understanding of their experience of caring for obese pregnant women and has made recommendations regarding specific training packages for health professionals that can be used to improve future training.

Improving care for obese pregnant women in the community

Investigators: Professor Dame Tina Lavender, Jacqui Clinton, Jane Brewin, Professor Colin Sibley

Funding: Study funded by Tommy’s through a grant from the Department of Health

Timescale: 2009–2012

Summary: This study is running alongside the ‘community exercise classes’ project. We aim to support obese pregnant women in Oldham and Bolton by offering a ten-week lifestyle programme, which they can attend with their children if they choose to. The lifestyle programme is multi-faceted, and includes physical activity, healthy eating, motivational techniques, personal care during pregnancy and social networking. To assess whether this programme is acceptable to women and has any impact on their weight, we are collecting information using various methods such as diaries, interviews, questionnaires and clinical records.

Investigating blood vessel damage in obese pregnant women

Investigators: Dr Mark Wareing, Dr Tracey Mills, Professor Philip Baker, Professor Colin Sibley

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2010–2013

Summary: One in five UK pregnant women are obese and at increased risk of complications such as pre-eclampsia. Fat produces proteins called adipokines, which are increased in obese non-pregnant individuals and damage blood vessels. We believe this also occurs in obese expectant mothers. We aim to determine the relationship between obesity, blood vessel function and adipokines in pregnant women. Our longer term aim is to advance new strategies to reduce the negative effects of obesity in pregnancy.

Metabolism throughout pregnancy in severely obese pregnant women in relation to infant birthweight

Investigators: Dr Shareen Forbes, Dr Rebecca Reynolds, Dr Fiona Denison, Graham Harold, Professor Jane Norman

Funding: Tommy’s funds the research midwife

Timescale: 2008 onwards

Summary: Studies in mothers who are overweight or obese have shown that they are more likely to have heavier babies with complications related to this increased birthweight. We wished to examine whether the levels of a substance derived from fat, known as ‘non-esterified fatty acid’ (NEFA), are higher in obese compared with normal-weight pregnant women and also whether there is a positive relationship between the mother’s NEFA level and her baby’s birthweight.

Progress report: In this study of 239 obese and 105 normal-weight mothers throughout pregnancy, we found that obese women had higher blood levels of sugars, fats and insulin at all points in pregnancy, and that in both groups the more weight a woman gained during pregnancy, the greater the birthweight of her baby. Higher sugar and lower insulin sensitivity of obese mothers at 28 weeks of gestation were predictors of larger birthweights. In the lean women, weight gain by 36 weeks, lower insulin sensitivity and lower NEFA at 28 weeks were predictors of large birthweight. Our study has shown how obesity disturbs the normal variations in sugar and fat metabolism that occur in pregnancy, and that these changes allow a greater fuel supply for the growing baby, leading to a larger birthweight. It also shows that some of the mechanisms of increased birthweight may be different in babies born to obese and lean mothers.

Intergenerational consequences of early-life ‘programming’ by maternal obesity

Investigators: Dr Vicky King, Rachel Dakin, Lincoln Liu, Professor Brian Walker, Patrick Hadoke, Professor Jonathan Seckl, Professor Jane Norman, Dr Mandy Drake

Funding: Tommy’s funds Dr King and most of the consumables for this study

Timescale: 2008–2012

Summary: Studies in humans and in animal models have shown that the ‘programming’ effects induced by exposure to an adverse environment in early life affect not only the directly exposed offspring but may also be transmitted to subsequent generations. The mechanisms which underpin this are unknown but are of great importance. We are investigating how the effects of maternal obesity affect not only the developing child, but how they might be passed on to the grandchildren and beyond.

Progress report: In contrast to other studies, we have found that perinatal exposure to maternal obesity is not associated with programmed effects in the first-generation offspring (but does have implications for second-generation offspring). The challenge is now for us to understand what is different about this study so that we can, in the future, give the best advice possible to pregnant women, in order to benefit both them and their children.

Maternal obesity and blood vessel stiffness during pregnancy

Investigators: Dr Fiona Denison, Dr Jeremy Langrish

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2009 onwards

Summary: In non-pregnant individuals, obesity is associated with high blood pressure and stiff blood vessels. Measuring blood vessel stiffness might provide a way to predict heart attacks or to screen for the risks of pre-eclampsia during pregnancy. However, the current methods of measurement are difficult in obese individuals and may therefore be less reliable. In addition, although obesity is associated with blood vessel stiffness in non-pregnant individuals, it is not certain whether the same relationship exists in obese pregnant women.

Progress report: We have completed our studies assessing blood vessel stiffness throughout pregnancy in obese and non-obese women, and we are currently analysing our results.

Maternal obesity and ‘programming’ of offspring obesity and cardiometabolic risk

Investigators: Dr Rebecca Reynolds, Dr Mandy Drake, Professor Amanda Lee, Dr Sohinee Bhattacharya, Professor Siladitya Bhattacharya, Professor Jane Norman, Keith Allan, Amanda Lee, Geraldine McNeill, Philip Hannaford

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2010–2012

Summary: Obesity is a major health problem in Scotland, particularly among women of childbearing age. Emerging evidence suggests obesity in pregnancy increases the risk of the offspring developing subsequent obesity and cardiovascular disease. In this study we are using a unique database, the ‘Aberdeen Maternity and Neonatal Databank’, to establish the magnitude of the link between maternal obesity and offspring cardiovascular disease and to begin to identify potential mechanisms. The database includes details on maternal weight and body mass index for all mothers who gave birth in the period 1966–1977. We are inviting these mothers and their children to participate in a study assessing obesity and cardiovascular risk.

Progress report: Of the 544 women invited to participate in the pilot study, 45 attended the clinical research facility, giving an overall response rate of 8%. The main reason for non-participation was that the study was carried out first thing in the morning, which was logistically difficult for many. Nevertheless, the study protocol was acceptable to all women who attended and could be completed within 1 hour. We have also continued with height and weight data entry for the whole Databank, and we now have a dataset for analysis that includes follow‐up of 37,709 offspring over a total of 1,323,275 person‐years. Analysis has shown than maternal obesity increases the risk of premature death in her offspring. As one in five women in the UK is currently obese at the time of antenatal booking, strategies to optimise weight prior to pregnancy are urgently required.

Barriers to breastfeeding in obese women

Investigators: Dr Fiona Denison, A Keely, Dr V Swanson, K Napier, M McCoy, Dr Jula Lawton

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2010–2013

Summary: Breastfeeding has significant benefits for maternal and offspring health. Unfortunately, breastfeeding rates in the UK are low compared to the rest of Europe, and a number of factors are thought to contribute to this. An emerging factor is maternal obesity, with studies finding that obese women are less likely to initiate and more likely stop breastfeeding earlier than normal-weight women. The reasons for this are, however, not well understood, thus limiting options for intervention. The aims of the study are to explore the factors that influence breastfeeding behaviour in obese compared to a non-obese women, determine the barriers to successful breastfeeding, and investigate access and provision of breastfeeding support.

Progress report: To date we have recruited 155 women. We have started to analyse the questionnaires and the qualitative interviews. It is evident that obese women have specific needs with respect to breastfeeding and may require tailored support for breastfeeding.

Liver function tests as an early predictor of gestational diabetes

Investigators: Dr Shareen Forbes, Dr Rebecca Reynolds, Dr Fiona Denison, Professor Jane Norman, Graham Harold, Professor Jane Norman

Funding: Tommy’s funds Ms Forson, Ms Greig and Mr Harold

Timescale: 2010–2012

Summary: The prevalence of gestational diabetes has doubled over the past decade, mirroring the alarming increase in obesity in the UK. Being able to predict which pregnant women are likely to develop gestational diabetes would allow intervention that may help ameliorate the associated adverse immediate outcomes during pregnancy and the longer term health complications to the mother and infant. The liver plays a central role in maintaining normal glucose concentrations during fasting as well as after meals, and is also a crucial site of insulin clearance. We are investigating whether liver function tests early on in pregnancy (at the 16 week booking visit) can predict gestational diabetes. 209 obese pregnant women and 109 pregnant women in a control group were recruited through the Tommy’s Edinburgh Antenatal Metabolic Clinic and liver function tests were carried out at various time points.

Progress report: We found that obese women display a unique pattern of liver function tests as their gestation progresses, compared with controls. In particular, the liver enzyme gamma-glutamyltransferase (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 28 weeks.

The accuracy of ultrasound fetal weight estimation in obese women

Investigators: Dr Fiona Denison, Dr Sarah Stock, Dr Shareen Forbes, Professor Jane Norman, Dr Rebecca Reynolds, Dr Jane Walker, Amelia Thomson

Funding: Tommy’s funds the research midwife and arranged the ultrasound scans for this study

Timescale: 2010–2012

Summary: In very severely obese pregnant women, it can be difficult to assess the size of the fetus using standard measurements such as the size of the uterus. Ultrasound is often used as an alternative method of assessing fetal size and to provide an estimate of birthweight. However, the accuracy of these measures in very severely obese women is not known. The aim of this study is to compare measurements of fetal size and estimates of birthweight in very severely obese compared to lean women.

Progress report: We have so far recruited 200 very severely obese and 99 lean pregnant women. To date, our studies suggest that ultrasound is not very accurate in assessing fetal size in either lean or obese women. However, ultrasound is no less accurate in severely obese women and may therefore be useful to inform the clinical care of these women. This study is ongoing and we are currently increasing the number of lean women recruited to this study and exploring alternative methods of calculating fetal weight and birthweight.

Weight gain during pregnancy

Investigators: Dr Shareen Forbes, Dr Fiona Denison

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2011–2012

Summary: Weight gain during pregnancy may be associated with having a large baby, which may have short-term consequences for the mother and baby, including operative delivery problems, as well as longer term problems such as later-life obesity. This study is investigating the weight gain in pregnancies from booking to delivery in women in Midlothian who do not have access to antenatal clinics where dieticians could offer advice. Our second aim is to examine attitudes to diet and exercise in this cohort.

Progress report: Of the 197 women participating in this study, only 33% gained weight within the recommended ranges, with the highest proportions of excessive weight gain seen in women who are overweight or obese. From interviews with the women, aquanatal exercise was the preferred form of exercise for most women although body image was a major factor limiting participation by obese women. We are currently working with our dietician to develop information leaflets to educate women and health professionals about weight gain during pregnancy.

Developmental origins of hypertension in children of obese mothers

Investigators: Dr Anne-Maj Samuelsson, Dr Paul Taylor, Professor Clive Coen (KCL), Professor Lucilla Poston, Dr Nina Balthasar (Bristol University)

Funding: Study taking place in a Tommy’s-funded centre

Summary: Obesity is an increasing problem among pregnant women worldwide. This research addresses the consequences of maternal obesity on the health of the child and into adulthood. Having previously shown that offspring of obese rodents develop raised blood pressure at a young age, we are now investigating the role played by mechanisms in specific regions of the brain which are known to control blood pressure. This study is investigating the ‘developmental overnutrition hypothesis‘, which proposes that excessive nutrition supply in early life may cause permanent changes in mechanisms involved in metabolic and cardiovascular control, which leads to early development of obesity and hypertension.

Body composition and gestational weight gain in severely obese pregnant women: associations with birthweight

Investigators: Dr Rebecca Reynolds, Dr Shareen Forbes, Dr Fiona Denison, Professor Jane Norman

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2012 onwards

Summary: Obesity and excessive weight gain during pregnancy have both previously been found to result in larger babies, which increases the risk of complications during delivery and disease in later life. We have been studying severely obese women and normal-weight women attending our Edinburgh Antenatal Metabolic Clinic. Body composition and weight gain were measured during pregnancy, with reference to the weight gain guidelines issued by the Institute of Medicine (IOM), which is part of the US National Academy of Sciences. These measurements were then compared with the birthweight of the baby.

Progress report: We found that severely obese women gained significantly less fat and overall weight during pregnancy than normal-weight women. Despite this, the severely obese women were more likely than normal-weight women to gain weight above the recommended guidelines, and they were more likely to deliver babies of excessive birthweight. It is crucial to not only encourage women to reach a healthy weight before becoming pregnant, but also to provide them with ways to maintain a healthy weight throughout pregnancy and to stress the importance of gaining weight within the recommended guidelines to ensure healthy outcomes for both mother and child.

Postpartum weight retention in severely obese women

Investigators: Dr Rebecca Reynolds, Dr Shareen Forbes, Dr Fiona Denison, Professor Jane Norman

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2011 onwards

Summary: If women fail to lose weight gained during pregnancy after childbirth they could be at risk of later life diseases such as heart attacks. There is currently no specific guidance available to women on weight loss after childbirth. This is particularly important among the obese group, who represent a growing sector of society and who remain largely un‐researched in terms of body changes following pregnancy.

Progress report: We have so far studied 141 obese and 69 lean women during pregnancy and after childbirth. At 6 months postpartum, severely obese mothers experienced an increase in an important type of fat, called ‘visceral’ fat, which is fat is located centrally within the body and is detrimental to health. Our findings suggest that, in order to prevent weight gain following childbirth, we should be targeting women either during pregnancy or in the immediate postpartum period. These findings could help provide guidance for health professionals with regard to the targeting of health promotion.

Epigenetic effects of maternal diabetes

Investigators: Dr Marian Aldhous, Dr Rebecca Reynolds, Robbie Lindsay, David Porteous, Professor Jonathan Seckl, Professor Jane Norman

Funding: Tommy’s funds the postdoctoral fellow (Dr Aldhous) and the consumables required for this research

Timescale: 2012–2014

Summary: The purpose of this study is to identify whether exposure to maternal diabetes in utero has a long-term adverse effect on the baby as it grows up. We also want to try to understand how these adverse effects are caused, and whether they can be predicted. We are using Generation Scotland, a large cohort of families in Scotland who have already agreed to participate in medical research, which provides very detailed clinical information, measurements, blood tests and DNA. The processes by which the maternal intrauterine environment has long‐lasting effects on offspring are unknown, but epigenetic mechanisms may play a role. These are modifications of DNA, without changing its actual sequence, that can affect which genes are expressed in specific tissues.

The effect of metformin on maternal and fetal body fat distribution

Investigators: Professor Jane Norman, Carolyn Chiswick, Scott Semple

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2010–2014

Summary: We are currently running a large double‐blind randomised controlled trial (EMPOWaR) to examine whether metformin, taken during pregnancy by women who are obese, is effective at reducing the risk of having a high birthweight baby. We are also interested in the effect of metformin on the pregnant woman’s body composition and fat distribution over the course of pregnancy, as well as the distribution of body fat in the developing fetus. We are doing this by using magnetic resonance imaging (MRI) scans.

Progress report: We continue to actively recruit women to the EMPOWaR study. The study is double-blind so the results will not be known until the last recruited patient has delivered her baby. However, analysis of the MRI images is in progress and confirms that our imaging protocols are working well.

Physical activity interventions in pregnancy and the postnatal period – what do women want?

Investigators: Dr Rebecca Reynolds, Dr Fiona Denison, Dr Zoe Weir, Hannah Carver, Professor Jane Norman

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2011 inwards

Summary: Exercise in pregnancy is safe and has considerable benefits for both mother and baby. However, studies encouraging exercise in obese pregnant women have largely been unsuccessful. In this project we are exploring severely obese women’s knowledge, attitudes and behaviours, including the perceived benefits and barriers, with regard to participating in physical activity during pregnancy and the postnatal period.

Progress report: Our findings suggest that most obese pregnant women are aware of the health benefits of exercise in pregnancy but lack knowledge of what is safe to do. There is an urgent need to develop suitable interventions to help women in pregnancy to overcome barriers to carrying out physical activity. We have now designed a feasibility study for an exercise intervention in pregnancy and we are currently conducting this among women attending our Edinburgh Antenatal Metabolic Clinic.

Investigating micronutrient intake in obese pregnant women

Investigators: Dr Rebecca Reynolds, Yvonne Greig, Professor Jane Norman

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2012–2013

Summary: Little is known in the UK about what obese pregnant women eat. This makes it difficult to design good guidelines for weight management in pregnancy. Our preliminary data shows that, despite eating a lot of calories, the nutritional content of obese women’s diets is not good. We know that more nutritious diets are better for the health and the development of the unborn baby. In this project we are assessing the nutritional contents of obese pregnant women’s diets by a combination of dietary questionnaires and measurements of essential nutrients in the blood.

Progress report: We have been investigating the nutritional status of severely obese and normal‐weight pregnant women attending our Edinburgh Antenatal Metabolic Clinic. The reported food intake in the obese group comprises an energy‐dense, micronutrient-poor diet with higher proportion of sugars, saturated fat and dietary cholesterol, and lower amounts of vital nutrients for pregnancy including iron, vitamin D and folic acid, than in the control group. Despite the high caloric intake, the obese women still fail to meet UK recommended values in pregnancy for these nutrients, and this is likely to have an adverse impact on offspring development. We are working with the dietician at our clinic to develop nutrient guidelines for severely obese pregnant women.

Investigating the mechanisms by which maternal age and/or obesity can affect the timing of birth and neonatal outcomes

Investigators: Dr Rachel Tribe, Rima Patel, Professor Lucilla Poston, Paul Seed

Funding: Tommy’s funds the laboratory consumables for this study

Summary: In Western societies, the age at which women conceive their first child is increasing and, together with the general increase in maternal body mass index, this is a cause for clinical concern, particularly in relation to problems with contractions, increased rates of induction, emergency caesarean section, difficulties in delivering the baby and the mother bleeding after delivery. Several studies have implicated advancing age in the mother or obesity as a factor leading to impaired uterine function and we are investigating this in a mouse model. We hypothesise that older mothers, who are also likely be of higher BMI, have impaired energy production in the muscle of the uterus (the womb) which leads to ineffective contractions during labour. Poor muscle activity in older mothers could also contribute to them failing to go normally into labour. Greater understanding about the changes in uterus muscle function associated with ageing and obesity could ultimately influence the way health professionals care for older mothers in pregnancy.

A low glycaemic index carbohydrate drink for obese pregnant women

Investigators: Professor Lucilla Poston, Paul Seed, Dr Stephen Thomas, Dr Nashita Patel, Eirini Platsa, Chloe Tucker, Dr Helen Murphy (University of Cambridge Metabolic Research Laboratories)

Funding: Study taking place in a Tommy’s-funded centre

Summary: Approximately 19% of women of reproductive age within the UK are considered obese. Obese women are at risk of developing diabetes in pregnancy because they cannot control their blood sugar as adequately as leaner women. This results in an increased supply of blood sugar to their babies, who are more likely to grow too large and to have too much body fat. This study is assessing whether providing women with a special drink (a low glycaemic index carbohydrate) to take with their meals can improve their blood sugar levels. Working with a commercial partner, we are testing several products in lean and obese pregnant women to determine the effect on the sugar in the mother’s blood. When we have found the best product, i.e. the one that best delays the rise in blood sugar after a meal, it will be used in a large clinical trial, as part of the large EU EarlyNutrition study.

Interventions in obese and diabetic pregnancy

Investigators: Dr Paul Taylor, Professor Clive Coen, Dr Anne-Maj Samuelsson, Dr Errol Richardson, Xanthi Maragkoudaki, Emmanuel Domfeh, Angelina Mouralideran

Funding: Study taking place in a Tommy’s-funded centre

Summary: Obesity in pregnancy can increase the risk of a poor obstetric outcome, including pre-eclampsia, high blood pressure during pregnancy and gestational diabetes. There is now increasing evidence that the consequences of maternal obesity extend beyond the pregnancy period and have adverse effects on metabolic and cardiovascular health in the child. We are currently investigating the underlying mechanisms involved in the non-genetic transmission of obesogenic and cardiovascular traits from mother to child, in an effort to optimise modifiable risk factors in obese pregnancy such as blood sugar. To this end, and with interest from a number of commercial partners and funding bodies, we are testing a range of potential therapeutic compounds, from dietary supplements to medicines, in a model of maternal obesity in rodents. We are examining the efficacy of these interventions in improving maternal health and the long-term health of the offspring. This investigation is designed to translate to, and inform, intervention strategies to improve health in childhood and beyond in infants born to obese mothers.

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Obesity and mental health in pregnancy

Investigators: Professor Louise Howard, Professor Lucilla Poston, Dr Dharmintra Pasupathy

Funding: Study taking place in a Tommy’s-funded centre

Summary: Obesity is a well-recognised risk factor for many pregnancy complications, including pre-eclampsia, gestational diabetes, emergency caesarean section and stillbirth. There is little information on the relationship between being overweight or obese and mental disorders during pregnancy, with conflicting data on whether there is an association, and how it may impact on pregnancy outcomes. This project is systematically reviewing the current evidence on obesity and mental health in pregnancy and will investigate the relationship between obesity, mental disorders and pregnancy outcomes so that future interventions can be developed to improve pregnancy outcomes in obese women.

Research projects into other areas of high risk pregnancy health

Can statins reduce the effects of maternal diabetes on the baby?

Investigators: Dr Melissa Westwood, Professor Colin Sibley, Professor John Aplin

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2010–2012

Summary: Babies born to mothers with diabetes are often bigger than normal. This can be a cause of illness in the newborn and these babies also have an increased chance of developing obesity, cardiovascular disease or diabetes in adulthood. The excess growth occurs in the later stages of pregnancy, probably as a result of the placenta growing too big and oversupplying nutrients to the baby. Our previous work suggests that statins – drugs usually used to lower cholesterol levels – might prevent this abnormal placental growth and function. In this study, we will use a mouse model of gestational diabetes to test whether giving statins results in offspring who have a normal birthweight and are healthy in later life.

Investigating the effect of maternal diet on offspring disease risk

Investigators: Dr Rebecca Reynolds, Dr Mandy Drake, James O’Reilly

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2009–2012

Summary: In recent years it has become clear that environmental factors might also increase the risk of disease in the offspring by changing the way that genes work (‘epigenetic’ changes), without actually causing mutations. This project is investigating the theory that maternal obesity or an unbalanced diet are associated with persistent epigenetic modifications in the offspring. For this study we are using placental samples from obese and lean women attending our Edinburgh Antenatal Metabolic Clinic.

Progress report: We have found that maternal weight correlates positively with expression of a number of key genes in the growth and glucocorticoid pathways in the early placental cells in the first trimester. In contrast, maternal weight appears to have no effect on placental expression of key genes at term. This suggests that early pregnancy may be a more important period for fetal and placental growth than later pregnancy, and that early pregnancy tissues may be more useful in studying the effects of maternal obesity during pregnancy. We plan to extend these studies to include women with preterm labour, delayed labour and stillbirth in studies supported by Tommy’s.

Can dietary supplements reduce cardiovascular disease risk?

Investigators: Dr Sue Ozanne, Dr Paul Taylor, Katharina Tilgner

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2009 onwards

Summary: Maternal nutrition can determine offspring health. A contributory factor may be a reduction in efficiency of the powerhouse of every cell, namely the mitochondria. We have identified a deficit of ubiquinone (CoQ), which is required for normal mitochondrial function, in the aorta of offspring in an experimental model. We propose that offspring supplementation with CoQ may have long-term beneficial effects and protect against cardiovascular disease. If successful, this study could lead to use of this safe dietary supplement for the prevention of cardiovascular disease and ageing arising from nutritional imbalance during fetal development.

Preventing excessive bleeding during childbirth: the STOP study

Investigators: Professor Susan Bewley, Annette Briley, Dr Mark Waterstone, Professor Jane Sandall, Henrietta Denney, Dr Rachel Tribe, Dr Graham Tydeman

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2008 onwards

Summary: Heavy bleeding, known as postpartum haemorrhage or PPH, remains a major cause of maternal death worldwide; in Europe it accounts for 13% of these deaths. The recently completed STOP study (‘Surveillance and Training in the Treatment of Postpartum Haemorrhage’) was an observational study identifying the current incidence, management and treatment for PPH. Qualitative data were also collected to explore the experience of PPH for women, their birth partners and the staff involved.

Progress report: The overall incidence of PPH in the two hospitals in the study was 34%. A number of known risk factors were confirmed: age, body mass index, placenta praevia, sepsis and previous ceasarean section. The following intrapartum risk factors were also confirmed: instrumental delivery, elective caesarean section and emergency caesarean section. The study also identified two new risk factors, namely assisted conception and Black African ethnicity. Once published, this study will inform guidelines for management of this common obstetric complication. Additionally it provides information for women, health professionals and policy makers when considering lifestyle, pregnancy choices, and mode and place of birth.

Identifying and responding to psychological distress and psychosocial risk factors in pregnancy

Investigators: Zoe Darwin, Dr Linda McGowan, Dr Leroy Edozien

Funding: Tommy’s part-funds the studentship for Ms Darwin

Timescale: 2008–2012

Summary: It is known that stress resulting from living conditions, life events and related pressures can adversely affect mother and baby during pregnancy. Maternity units enquire about these issues when a woman books for antenatal care but reliable tools for detecting the broad range of factors leading to stress are not available. This study is assessing a combination of tools for identifying vulnerable women and ways of supporting such women.

Progress report: Maternal stress was found to be common. While anxiety was a major concern, hospital staff tended to focus on depression. A tool 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. The findings of this research will inform the development, implementation and evaluation of low-cost resources for women with maternal stress.

Renal disease arising from early catch-up growth

Investigators: Professor Lucilla Poston, Dr Sue Ozanne (University of Cambridge), Dr Paul Taylor, Katharina Tilgner

Funding: Study taking place in a Tommy’s-funded centre

Summary: Low birthweight is associated with an increased risk of cardiovascular, metabolic and kidney disease in later life. In this project we are investigating how poor fetal growth can lead to renal dysfunction in the offspring and ultimately facilitate accelerated renal ageing. To replicate fetal growth restriction we have chosen a rat model of maternal protein restriction. Our collaborators in Cambridge have developed a hypothesis of how protein restriction in the mother can lead to renal ageing in the offspring. We are investigating at which point in the offspring’s life a deterioration of renal function can be observed, and whether it involves the development of hypertension.

Designing a device to release suction in emergency caesarean section (the Tydeman Tube)

Investigators: Annette Briley, Dr Graham Tydeman, Professor Andrew Shennan

Funding: Study taking place in a Tommy’s-funded centre

Summary: More than a quarter of babies born in the UK are delivered by caesarean section. If performed during the first or second stage of labour, the baby’s head is often very far down in the pelvis and a vacuum is created between the baby’s head and the womb and it is very difficult for the surgeon to remove the baby. No completely safe methods of releasing this partial vacuum have yet been developed. The purpose of this project is to commercially develop a device (the Tydeman Tube) that can be placed between the baby’s head and the womb to release the suction created and therefore make it easier for the surgeon to deliver the baby more rapidly. In a parallel project, we are developing a suitable mannequin that will allow us to refine the design of the device and that will also be used to train obstetricians.

Progress report: An independent product design consultant is now negotiating with a manufacturer about the production of the final design under licence.

Designing a device to facilitate caesarean section (Desperate Debra)

Investigators: Annette Briley, Dr Graham Tydeman, Professor Andrew Shennan

Funding: Study taking place in a Tommy’s-funded centre

Summary: Caesarean sections undertaken in the late first and second stages of labour are often technically more difficult than those performed earlier in labour. This is because the fetal head is much lower in the maternal pelvis and the uterine contractions form a partial vacuum between the fetal head and maternal soft tissues. The operator must overcome this vacuum in the limited available space before the baby can be delivered. We have developed a new device (the Tydeman Tube) which is designed to release the vacuum and facilitate delivery. During development of the device, it became clear there was a need for a mannequin not only to test the device but also to help train clinicians in these difficult deliveries.

Progress report: The device, Desperate Debra, is a medical simulator to assist midwives and obstetricians to gain experience and confidence in correctly determining and manipulating the position of the fetal head during caesarean sections. The prototype has been developed and it is currently being externally evaluated by clinicians, prior to commercial production. There has been considerable media interest in this project and Dr Tydeman and the research team at St.Thomas’ won the Innovation Award at the 2012 Guy’s and St Thomas’ NHS Foundation Trust Awards.

Designing a training simulator for amniocentesis

Investigators: Annette Briley, Dr Graham Tydeman, Professor Andrew Shennan

Funding: Study taking place in a Tommy’s-funded centre

Summary: Amniocentesis is a diagnostic procedure carried out in early pregnancy to detect genetic abnormalities in the fetus. The procedure is not without risk and those who carry it out should first be adequately trained on a simulator. This project is designing an improved simulator for clinician training.

Progress report: A basic model has been designed and built, taking into account the concerns of clinicians. We are working with a device manufacturer to develop the product further.

Smoking cessation in pregnant women with mental health problems

Investigators: Professor Louise Howard, Professor Theresa Marteau, Professor Susan Bewley, Jill Demilew, Deborah Bekele, Melissa Rowe

Funding: Study taking place in a Tommy’s-funded centre

Summary: Smoking in pregnancy is one of the most important risk factors for low birthweight, very preterm birth and perinatal death. There is increasing evidence that smoking cessation services in pregnancy reduce the proportion of women who continue to smoke. Mental health problems and cigarette use among pregnant women are strongly associated and we have investigated the reasons why some women with mental health disorders are able to stop smoking while others cannot. We have interviewed women who have continued or stopped smoking since antenatal booking, and do or do not have mental health problems, to investigate women’s attitudes towards smoking during pregnancy, knowledge about the effects of smoking on themselves and their baby, knowledge about the effectiveness of help with stopping smoking during pregnancy and attitudes towards different types of interventions.

Progress report: We found that pregnant smokers with a mental disorder are more likely to accept referral to smoking cessation services but even so they are more likely to still smoke at delivery. They and their health practitioners do not prioritise smoking advice due to concern about adversely impacting their mental health. We conclude that pregnant women with mental disorders appear more motivated, yet find it more difficult, to stop smoking. Prioritisation of mental health over smoking may thus lead to increasing health inequality for this group. These results are being disseminated to local, national and international maternity and mental health services to improve the frequency and nature of the interactions between healthcare professionals and pregnant women with mental disorders who are smoking in order to facilitate higher quit rates in pregnancy.

The Birthplace in England research programme

Investigators: Professor Jane Sandall, Jennifer Hollowell (University of Oxford)

Funding: Study taking place in a Tommy’s funded centre

Summary: The NHS in England currently provides services for birth in four types of setting – hospital obstetric units (OUs), midwifery units provided alongside an OU (AMU), freestanding midwifery units (FMUs), and at home. Many NHS trusts, however, provide only a limited range of services. The results of the Birthplace cohort study show that, for low-risk women, giving birth is generally very safe. MUs appear to be safe for babies and to offer benefits for women in terms of reduced intervention. For women having a second or subsequent baby, home birth and MU birth appear to be safe for the baby and to offer benefits for the mother. However, for women having a first baby, home birth increases the risk of a poorer outcome for the baby. For women having a first baby there is a fairly high chance of being transferred to an OU during labour or immediately after the birth, though for women having a second or subsequent baby the chances are much lower. This research will use the data collected in the Birthplace programme to answer a number of questions that have not yet been addressed. In particular, the research will explore differences in service delivery between NHS trusts and compare rates of transfers, outcomes and interventions for women. An important set of questions arises in relation to the care of women with complications or risk factors who elect to give birth in non-obstetric settings. This study will explore these questions in relation to both clinical outcomes and the organisation of care. The information provided by this research will help managers plan how maternity services are organised and give more information to women, and those caring for them, in order to help women make an informed choice about their planned place of birth.

A review of workforce deployment and skill mix in maternity care

Investigators: Professor Jane Sandall, C Homer, I Bourgeault, Professor Susan Bewley

Funding: Study taking place in a Tommy’s funded centre

Summary: Staff deployment has been identified in numerous reports as being a critical component of safe maternity care. This project reviewed the relationship between maternity workforce staffing, skill mix and deployment practices on the safety of maternity care. Rearranging services around women has benefits for women and babies.

Progress report: The final report has now been published and the main conclusions are the following. Midwife-led models of care should be deployed across the service for low- and medium-risk women, releasing obstetricians to focus on women with more complex needs. Nurses could be used more widely to free up the time of midwives and doctors. The role of maternity support workers should be explored – clarity and consensus is required nationally over what the role should involve in order to ensure that robust oversight and accountability processes are established.The deployment of both midwives and doctors should be reviewed in out-of-hours services to ensure the availability of sufficiently experienced and senior staff. Continuity of care should be encouraged – the use of continuous lay support during labour, in addition to clinical care, shows potential to improve women’s experience and should be further explored by services in the UK. There is a need for high-quality research into the effectiveness of new and emerging models of care where there is potential for cost savings while maintaining levels of safety – particular areas of potential include the use of maternity support workers and doulas and the shifting of tasks between nurses, midwives and doctors. Further research into the Birthrate Plus tool would be of value in assessing whether it could be developed to allow effective planning across the different professions.

Position during labour in women with an epidural (the BUMPES study)

Investigators: Professor Geraldine O’Sullivan, Professor Andrew Shennan, Professor Deborah Bick, Professor Peter Brocklehurst (UCL)

Funding: Tommy’s part-funds this project

Timescale: 2010–2012

Summary: There is uncertainty whether different positions adopted by women with epidural analgesia, in the late stages of labour, can assist women in having a straightforward delivery. The BUMPES trial is recruiting women in labour with their first baby, who have had an epidural. The trial will evaluate whether adopting a policy of an ‘upright position’ throughout the second stage of labour is associated with an increase in the incidence of spontaneous vaginal (normal) delivery compared with a policy of adopting a ‘lying down’ position. The trial is also comparing the length of time labour takes and the level of satisfaction with the experience for women. The trial will recruit 3,000 women over 33 months in at least five large hospitals in the UK. St Thomas’ Hospital is a pilot site.

Prediction of large for gestational age infants

Investigators: Dr Dharmintra Pasupathy, Professor Lucilla Poston, Professor Magnus Westgren (Karolinska Institute, Sweden)

Funding: Study taking place in a Tommy’s-funded centre

Summary: In developed countries the number of infants born with high birthweight has increased by 25% over the last 20 years. The complications associated with delivery of these infants, such as infant death, severe birth trauma, caesarean section, blood loss at delivery and childhood obesity are increased. The number of infants born too large is set to increase even further as the number of pregnant women who are obese, have diabetes or are older is increasing worldwide. A test that could predict birthweight in the early weeks of pregnancy would help improve the chance of a safe delivery. The aim of this study is to develop a test that will help accurately identify which women are likely to have a large baby and so contribute to better care for the mother and baby.

Investigating the effect of maternal stress on fetal growth

Investigators: Dr Rebecca Reynolds, Professor Jane Norman, Dr Fiona Denison, Professor Jonathan Seckl

Funding: Study taking place in a Tommy’s-funded centre

Timescale: 2012–2013

Summary: There is increasing evidence that maternal stress has long-term adverse effects on outcome for the baby but the pathophysiological pathways are unknown. In this study, we plan to use MRI scans to investigate whether maternal stress has a direct effect on fetal brain growth and development in utero. If we can show this, it would support intervention studies to reduce stress in pregnancy. The ability to accurately measure brain growth in specific areas of the brain is likely to be highly valuable – our study is also a proof of concept in this regard.

The contribution of modifiable factors to uncomplicated pregnancy (part of the SCOPE/MAPS study)

Investigators: Dr Lucy Chappell, Paul Seed

Funding: Study taking place in a Tommy’s funded centre

Summary: We have used information from the large SCOPE study (known as MAPS in the UK) to look at what increases and what decreases a woman’s chances of having a normal pregnancy. We considered both factors that could be changed and those that could not. Being overweight or obese, having high blood pressure, using illicit drugs in early pregnancy, and being deprived all reduced the chances of a normal pregnancy. Eating plenty of fruit before pregnancy, and being in work increased the chances of a normal pregnancy. Factors that could not be changed but which reduced the chances of a normal pregnancy were her mother or sister having had high blood pressure in pregnancy, the woman having had high blood pressure if she had taken the contraceptive pill, vaginal bleeding in pregnancy or an abnormal blood flow scan at 20 weeks of pregnancy. We hope that understanding the factors that can be changed can help healthcare professionals and women to increase the chances of normal pregnancy, and thus reduce the complications that are seen with preterm delivery and pre-eclampsia.

Maternal type 1 diabetes and adverse outcomes in large for gestational age infants

Investigators: Dr Dharmintra Pasupathy, Dr Martina Persson (Karolinska Institute, Sweden)

Funding: Study taking place in a Tommy’s funded centre

Summary: Pregnancies complicated by high-birthweight infants have a number of increased risks. There are complications with both short- and long-term consequences for both the mother and the infant, including postpartum haemorrhage, caesarean delivery, birth damage to the infant and lack of oxygen at birth. The current definitions of high birthweight do not account for body composition and shape, which may also have an effect on the risk of adverse outcome. It is also recognised that the risk of problems is higher in women with type 1 diabetes. In this project we aim to study the complex interaction between birthweight, diabetes and history of previous birth on the risk of adverse birth outcomes to the mother and the infant. Being able to identify pregnancies at higher risk of birth complications will allow the most suitable care to be provided.

Investigating the relative growth rate of twins in the womb

Investigators: Dr Dharmintra Pasupathy, Dr Argyris Stringaris (Institute of Psychiatry, KCL); Dr Thalia Eley (Institute of Psychiatry, KCL)

Funding: Study taking place in a Tommy’s-funded centre

Summary: There is a lot of evidence that the prenatal environment affects both physical and psychological development in the offspring. In this study we are investigating the relative contribution of genetic influences and the prenatal environment on childhood emotional and behavioural problems. To achieve this, we are studying twins, who are either identical and share 100% of their genes, or non-identical and share 50% of their genes. This will enable us to tease out the relative contributions of genes and the environment to emotional and behavioural problems. Using data from all twins delivered in St Thomas’ Hospital between 2005 and 2012, we are also examining the antenatal growth patterns. We will try to identify antenatal predictors of abnormal fetal growth and adverse birth outcomes, using ultrasound growth records and routinely collected pregnancy and birth outcome data. Mothers of twins have been contacted and invited to provide detailed information on the twins’ emotional and behavioural development. We are now in the final stages of recruitment to the study, after which the data will be analysed.

The efficient use of the maternity workforce and the implications for safety and quality in maternity care: an economic perspective

Investigators: Professor Jane Sandall, Kirstie Coxon, Rod Gibson

Funding: Study taking place in a Tommy’s funded centre

Summary: The performance of maternity services has been seen as a touchstone of whether the NHS is delivering safe, high-quality health services. In essence, the key challenges are to improve productivity and quality of maternal healthcare outcomes, including safety, and understand how the maternity workforce can be organised to rise to these challenges. Few, if any, studies have considered the potential trade-offs between staff groups to optimise quality and efficiency nor have they attempted to explore the effects of these on different outcomes simultaneously. Therefore the aim of this project is to explore the relationships between maternity workforce size, skill mix and quality outcomes including patient safety, effectiveness and efficiency. We will also model the effects of various workforce configurations on both quality (measured by safety outcomes) and productivity.

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Risks and benefits of antipsychotic medication in pregnancy for women with psychotic disorders

Investigators: Professor Louise Howard, Dr Dharmintra Pasupathy

Funding: Study taking place in a Tommy’s funded centre

Summary: There is very limited information available about the risks and benefits of antipsychotic medication in pregnancy for women with a history of or a current severe mental illness, such as schizophrenia or bipolar disorder. This project will provide evidence on the risks and benefits of psychotropic drugs in pregnancy through analyses of data from the Case Register Interactive Search (CRIS) system, which is a unique anonymised mental healthcare database. It has recently been linked to maternity Hospital Episode Statistics (HES) data, allowing maternity outcomes to be investigated. Data will be extracted on a large cohort of pregnant women with psychotic disorders to investigate the impact of medication changes and other predictors of maternal psychiatric and obstetric outcomes.

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Placental homing peptides and targeted drug delivery in pregnancy

Investigators: Natalie Cureton, Anna King, Cornelia Ndifon, Dr Lynda Harris

Funding: Study taking place in a Tommy’s funded centre

Timescale: 2010–2015

Summary: Several potential therapies for pregnancy diseases have been shown to improve placental function in laboratory experiments, but there is no means of safely delivering them to the placentas of pregnant women. To address this need, we are developing a targeted drug delivery system suitable for use in pregnancy. By restricting the actions of suitable drugs to the placental surface, women will feel more confident that any treatment they receive during pregnancy will not harm their unborn child. It has recently been discovered that every organ in the body expresses a unique combination of molecules on its surface, giving it a unique identity or molecular ‘postcode’. By studying the molecular postcode of the placenta we have identified a series of ‘placental homing peptides’, which, when injected into the bloodstream of pregnant mice, bind only to the surface of the placenta and not to any other organ. By coating drugs with placental homing peptides, they can be targeted directly at the placenta. This idea will be tested using mouse models of pregnancy complications, to assess the ability of targeted drug delivery to improve placental function and enhance fetal growth. As all our homing peptides also bind to human placental tissue, this strategy may be used to treat pregnancy complications in women in the longer term.