Updated February 2015

The Royal Infirmary, Edinburgh

Tommy’s third research centre, at the Royal Infirmary of Edinburgh, was opened in April 2008. Led by Professor Jane Norman, the focus of the team is on discovering ways to alleviate the risks and problems caused by maternal obesity. Other areas of research interest include blood vessel and tissue remodelling, fetal ‘programming’, inflammation, hypoxia and the process of labour and childbirth and maternal depression/stress.

Situated in the state-of-the-art buildings of the Queen’s Medical Research Institute, the centre is helping to make Tommy’s maternal and fetal research network a truly major force worldwide. It has 35 core staff and in 2013/2014 published 59 scientific papers in the pregnancy field in peer-reviewed medical journals. The centre has developed excellent collaborative links with the sister Tommy’s centres in London and Manchester, as well as with other relevant groups within Edinburgh and beyond. A major achievement has been the award of Centre status from the Medical Research Council (MRC), with the MRC Centre for Reproductive Health opening in April 2011. The Tommy’s centre is an integral part of the MRC Centre and is key to one of its main themes: ‘Developmental programming and reproductive resilience’.

The centre opened the Tommy’s Antenatal Metabolic Clinic in August 2008 and it is now providing specialised care to around 200 obese pregnant women per year. This clinic provides the infrastructure for most of the centre’s work on obesity in human pregnancy, and it has become a template for similar clinics around the UK.

Core funding from Tommy’s has allowed the Edinburgh centre to develop new research threads that are crucial for better understanding and treatment of complications associated with pregnancy.

Lecture from Professor Jane Norman on pregnancy research in Edinburgh

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Current research areas at Edinburgh

 

The AFFIRM randomised trial for prevention of stillbirth

Rates of stillbirth in the UK are amongst the highest in resource-rich countries. The majority of stillbirths occur in normally formed infants, with (retrospective) evidence of placental insufficiency being the most common clinical finding. Maternal perception of reduced fetal movements is an early marker both placental insufficiency and subsequent stillbirth. The AFFIRM study will investigate whether the introduction of a package of care for women with reduced fetal movements reduces stillbirth. The package of care includes education to increase pregnant women’s awareness of fetal movements and prompt reporting of reduced fetal movements, followed by a standardised management plan for identification of placental insufficiency with timely delivery in confirmed cases. When a similar package was introduced in Norway, the frequency of stillbirth fell by 30% but the efficacy of this intervention has not been robustly tested in a randomised trial (the best form of evidence). Hospitals in Scotland, Ireland, England and Wales will be randomised to the timing of introduction of the care package. A smaller study will examine the acceptability of the intervention to patients and healthcare providers and identify any barriers to implementation. We have had huge interest in this study, with 29 sites and around 450,000 pregnant women scheduled to participate. Tommy’s Dr Alex Heazell, Professor Jane Norman and Dr Sarah Stock have been launching the trial in various centres. Recruitment of women started in May 2014, and the trial will be completed in Spring 2016. This study has the potential to directly improve stillbirth rates. 

Metformin for reducing excess birthweight in the babies of obese pregnant women (the EMPOWaR study)

In the EMPOWaR clinical trial, 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. The trial was initially scheduled to recruit women from Edinburgh and Liverpool only. However, we have had huge interest from other centres and we are currently recruiting from Edinburgh, Liverpool, Coventry, Sheffield and Nottingham. We have now randomised 449 obese pregnant women to treatment with metformin or placebo. The study has received considerable press attention in the UK and overseas, including an interview with Professor Jane Norman on the Radio 4 ‘Today’ programme. 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 investigating this by using magnetic resonance imaging (MRI).

Glibenclamide and metformin versus standard care in gestational diabetes (the GRACES study)

Gestational diabetes is a common condition and currently women who are not adequately treated on metformin (an oral tablet) have to self-administer subcutaneous insulin. This is invasive and unpleasant. In non-pregnant people with type 2 diabetes, the tablet glibenclamide is used together with metformin to treat diabetes. We hypothesise that addition of glibenclamide to metformin (combination therapy) will reduce the number of pregnant women with gestational diabetes who require insulin, without compromising glycaemic control or adversely affecting other clinical outcomes. This feasibility trial will inform the design of a future substantive multicentre trial to test this hypothesis. Ethical approval for this study has recently been obtained and women are now being recruited. If this research is successful, it will demonstrate a much better way of managing diabetes in pregnancy. 

The effects of stress hormones in obese and non-obese women

Over-exposure of the developing baby to the steroid stress hormone cortisol results in low birthweight. The levels of this hormone increase during normal pregnancy and they are also altered in obesity, but we need to understand how they change in obese pregnant women. We are also using MRI scans to investigate whether maternal stress has a direct effect on fetal brain growth and development. 

Progesterone: could it prevent premature birth?

Although the main focus of the centre is on obesity, it is also handling a major clinical trial (the OPPTIMUM trial) to see whether giving high-risk women progesterone between 22 and 34 weeks of gestation will reduce the incidence of preterm birth. Recruitment of women was completed in 2013 and this is now the largest trial of progesterone in the world, with over 1,200 women randomised to receive progesterone or placebo. We are now in the baby follow-up stage and results should be available in 2016. 

Can omega-3 fish oils reduce inflammation of the fetal membranes?

Preterm labour affects around 6% of pregnancies in Scotland and, despite great advances in neonatal care, prematurity remains the leading cause of death and disability in newborn babies. There are currently no effective treatments to prevent premature delivery, and factors controlling the onset of labour remain poorly understood. We have found that omega-3 fatty acids do 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.

Using MRI to study placental physiology and to detect intrauterine hypoxia

Many pregnancy complications such as pre-eclampsia, fetal growth restriction and diabetes are associated with poor placental function but there are no tests currently available which are able to assess placental function. A diagnosis of a ‘sick’ placenta is therefore only made relatively late in pregnancy. We have carried out a successful pilot study to evaluate the feasibility of using magnetic resonance imaging (MRI) to investigate uteroplacental physiology during pregnancy. We are also using our powerful MRI scanners to investigate hypoxia (low oxygen levels) within the womb, with very encouraging results. In the longer term, we hope that novel imaging techniques will be able to provide information to help decide on the timing of delivery and thus improve outcome in pregnancies complicated by uteroplacental insufficiency. 

New ultrasound techniques to diagnose fetal infection

Infection that occurs in the womb in pregnancy can harm the developing baby and result in preterm labour. Often these infections have no overt signs in the mother. A major problem is thus recognising pregnancies that are affected with infection, so that treatments can be targeted and delivery timed to optimise outcomes for babies. We are developing a non-invasive ultrasound technique for monitoring a developing baby’s wellbeing and response to infection. We will first determine the potential of these new techniques in a study in sheep, which will indicate whether clinical trials in humans are feasible.

Epigenetic effects of maternal diabetes

We are studying whether exposure to maternal diabetes in the womb has a long-term adverse effect on the baby as it grows up. 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. 

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

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 recently completed project we explored 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. Our key results were that several perceived barriers to physical activity during pregnancy were described, including personal, societal and support barriers. Walking was reported as being the most popular activity in pregnancy. The majority of women (71%) reported a decrease in their physical activity levels as their pregnancy progressed, with 50% reporting a decrease in their confidence to maintain/increase activity. 78% of women used the physical activity information leaflet provided, and 77% of those who trialled the pedometer said they found it a useful tool. In summary, these data show that future lifestyle interventions designed for morbidly obese women in pregnancy should take into account individual, societal, and professional barriers to weight management in pregnancy.

Establishing a resource for the study of genetic associations with preterm labour

Both genetic and environmental factors contribute to a woman’s risk of spontaneous preterm birth. Advances in genetic and bioinformatic technologies now provide potential for these complicated interactions to start to be understood and for an individual’s chance of delivering early to be determined. We want to establish a biobank of samples for studies of genetic associations with preterm birth. However, uncertainty about the best way to involve pregnant women and the most efficient way to collect and analyse samples and data means that a pilot study is needed. We are recruiting woman who are participating in another trial (the OPPTIMUM trial – a randomised trial of progesterone pessaries to prevent preterm labour) to pilot the recruitment and sample collection methods. This pilot study will provide valuable information for future preterm birth research.

A pilot study of the Arabin pessary for preventing preterm birth

A recent randomised trial suggests that the Arabin pessary, applied in unselected women with a cervical length of less than 25mm, is highly effective in reducing preterm birth. Although this trial was published in the Lancet, concerns have been expressed about the higher than expected incidence of preterm birth in the ‘placebo’ group (27%) and that the final sample size was less than half that originally planned. Many authorities have suggested that the findings should be replicated before the pessary is introduced into clinical practice. The Arabin pessary is inexpensive and easy to use. If it is effective in preventing preterm labour in women with a short cervix then it has the potential to be used in both developed and developing countries. This will have major benefits, particularly for developing countries, where neonatal death rates following preterm delivery are very high because specialised neonatal care is either not available or very limited.

Home blood pressure monitoring in pregnancy using telemetry – the BLOSSOM study

Women with hypertensive disorders in pregnancy require more frequent monitoring of their blood pressure during the antenatal period. This results in more appointments with their community midwife or attendance at the hospital’s Day Assessment or Triage department for monitoring. We are investigating whether substituting these visits with home monitoring of blood pressure using telemetry is an acceptable method to women and what impact this has on the service. Preliminary results indicate that women prefer home telemetry for blood pressure monitoring, with the majority of women stating that they find the blood pressure monitor easy to use and that they prefer monitoring their blood pressure at home as opposed to attending hospital.

Telemetric monitoring of blood sugar levels in pregnant women with diabetes

Women with pre-existing diabetes or with gestational diabetes have an increased risk of developing serious problems during pregnancy. Optimisation of blood sugar levels greatly reduces these risks and thus these women have intensive (largely hospital-based) monitoring during pregnancy with frequent attendances at antenatal or diabetes clinics where they are reviewed together or separately by obstetricians and diabetologists. This is labour and time intensive for all involved and does not promote the women’s self-management of their condition. With the dramatic increase in number of women with diabetes, this model of care is not sustainable. In this project we are exploring the feasibility of using telemetry-supported monitoring of blood sugar control to improve the management, care pathway and patient experience for pregnant women with diabetes. 

Role of androgens in uterine contractions

Preterm birth is a major cause of neonatal morbidity and mortality. It is important that spontaneous uterine contractions prior to term be avoided. Some androgens, including testosterone and its metabolite dihydrotestosterone, increase as pregnancy progresses but we don’t yet understand their role in myometrial (uterine muscle) contractility. We have been examining the action of androgens on spontaneous myometrial contractility on tissue samples obtained from pregnant women at term undergoing caesarean delivery. We have found that exposure to either of these androgens rapidly inhibits spontaneous contractions. Further understanding of how androgens reduce myometrial contractions will help us to understand what causes new preterm labour and to develop new treatments. 

 

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The Edinburgh Antenatal Metabolic Clinic

The effects of maternal obesity

With around half the women of childbearing age in the UK now overweight or obese, the impact of obesity in pregnancy continues to be a major issue, both to the immediate outcome in pregnancy and to the long-term health of the child. Government projections for Scotland suggest that, without clear action, obesity figures will rise to almost nine in ten adults and two-thirds of children by 2050. This matters because of the severe impact being overweight or obese can have on an individual’s health - both are associated with an increased risk of diabetes, cancer, heart disease and massive complications during pregnancy. In addition, a report by CEMACH (Confidential Enquiry into Maternal Deaths) has shown that obese pregnant women are probably at four or five times greater risk of maternal death than a woman of normal weight - and the same for their babies dying.

The associated risks in pregnancy for obese women include increased chances of miscarriage, stillbirth, pre-eclampsia, gestational diabetes, neonatal obesity and preterm birth. These preterm babies are at much greater risk of blindness, deafness, cerebral palsy and developmental delay - disabilities which can bring a lifetime of suffering.

Emerging evidence also suggests that maternal obesity has long-term consequences for the baby, including childhood obesity and increased risk of developing heart disease and diabetes in later life. Studies have shown that part of the reason behind this is the poor diet of the mother while pregnant, which in turn makes the baby more likely to crave a similar diet themselves. The baby is, as such, ‘programmed’ in the womb by an adverse fetal environment during pregnancy.

Consequently, this is the first generation in human history where the health of the children will be worse than that of their parents and the cycle of disadvantage is passed from one generation to the next.

The importance of additional clinical care

There is very little help available for people who are obese and pregnant in Scotland. Health professionals rarely intervene, partly because there are very limited options available to help obese people and partly because it often impacts on the midwife or doctor/patient relationship, making individuals less likely to see their midwife or doctor. The situation is exacerbated during pregnancy as women tend to increase weight from one pregnancy to the next.

Tommy’s is determined to tackle the problems of maternal obesity, both through research and through providing high-quality clinical care. The first major achievement of the Edinburgh centre was to open a new Antenatal Metabolic Clinic, jointly funded by Tommy’s, Lothian Health Board and the University of Edinburgh, at which obese mothers are monitored throughout their pregnancy. In addition to providing valuable data for our research scientists, our clinic ensures that these women get a far higher standard of care than they would otherwise.

The clinic is going from strength to strength and sees around 200 obese pregnant women (with a body mass index (BMI) of 40  or more) per year. The clinic is multidisciplinary, with care being provided by obstetricians, endocrinologists, dieticians and a psychiatrist (where appropriate). Not only is this type of specialist treatment and care helping to reduce the prevalence of pregnancy complications in obese pregnant women who attend the clinic, but it is also crucial in facilitating research into mechanisms and treatment.

Midwifery support underpins the success of the clinic. The midwife liaises with the women, engaging their support to attend the clinic. The care package is arranged by the midwife and tailored to the individual needs of the women. We also have support from the community midwives and the majority of referrals to the clinic come from them.

The enhanced care package includes additional detailed scans and growth scans, glucose tolerance tests (a test for gestational diabetes), post-dates monitoring, a thorough anaesthetist’s assessment, and the prescribing of drugs to prevent deep vein thrombosis.

 

We have also set up postnatal follow-up clinics for mothers and babies who attended the Antenatal Metabolic Clinic. During these consultations we discuss any problems which occurred during pregnancy, reinforce healthy lifestyle advice for both mother and baby, and discuss issues for future pregnancy. We have been following up the babies of these women, with 255 attending at 3 months and 194 attending at 6 months of age so far. Preliminary analysis shows that infants in the obese cohort were significantly heavier and shorter at birth and remained significantly heavier by 6 months. Postnatal influences such as breastfeeding less and early introduction of solid foods may be a cause for this observation and impact on obesity in later childhood years.

We have recently obtained ethical and R&D approval to carry out a follow-up study of the infants, who are now aged between 3 and 7 years, to assess growth and the development of obesity and any metabolic problems.

During the initial clinic set-up we sought informal feedback from the women who attended the clinic. This was very positive, with women appreciating the care and additional support provided for them by the clinic. We have now begun to see a number women coming back to the clinic for their second pregnancy.

Key recent achievements at the Edinburgh research centre

We’ve shown that maternal diabetes has lifelong adverse effects in the offspring

Our analysis of data from Generation Scotland, a large cohort of families in Scotland who have agreed to participate in medical research, showed that maternal diabetes is associated with higher percent body fat, raised blood pressure and an increased the risk of metabolic syndrome (which increases the risk of heart disease) in the offspring. These results have clear public health implications and demonstrate the adverse effects of maternal diabetes on long-term outcomes for the baby. Essentially, they show that being exposed to diabetes in utero has major significant effects on lifelong health. We hope that these data will help pregnant women to understand how important it is to maintain blood sugar levels within normal limits during pregnancy. Additionally, they confirm how important pregnancy health is to the health of the offspring in future generations.

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 shown that induction of labour does not always need to be initiated in hospital

We have found that the first part of the induction of labour process, where a hormone gel is used to soften and dilate the cervix, can be safely carried out at home. Outcomes are similar to when this process is carried out in hospital.

We've shown that elective caesarean section is safer for the baby in women who have had a previous caesarean section

We have found that induction of labour in women who have had previous caesarean delivery increases the risks of complications for the baby. In these women, repeat elective caesarean section is safer for the baby than induction of labour or allowing spontaneous labour.

We’ve found that risk of preterm labour can be inherited

In a study of the Aberdeen maternity databank, we found that women whose mother or grandmother had a preterm birth are more likely themselves to have spontaneous preterm labour. This implies that there is a ‘genetic’ component to preterm birth, which may allow techniques for early detection and treatment to be developed. 

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 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 found that progesterone does not reduce preterm birth in twins

Although progesterone reduces preterm birth in women with one baby, we found that it did not reduce preterm birth (if anything, it increased it) in women with a twin pregnancy. This study is important in preventing women with twin pregnancy getting an ineffective treatment. Accordingly, the results were published on a ‘fast track’ basis in the Lancet medical journal and were accompanied by an editorial.

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 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 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 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 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 Iit  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 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.

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

In our AMPOP metabolic study 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 identified novel strategies that may promote brain repair in preterm infants

There is increasing acceptance that strategies to prevent preterm labour will not improve the outcome for the baby unless they are accompanied by strategies to prevent perinatal brain injury. We have established a novel model of perinatal brain injury that is the first to replicate the full range of neuropathology observed in the brains of infants with this injury. Our recent studies give us insights into how best to prevent or potentially treat brain injury associated with infection-induced preterm birth.

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. 

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