Pregnancy complications

The need for rigorous research into the common pregnancy complications of fetal growth restriction (FGR), pre-eclampsia (PE) and preterm labour (PTL) occur on a global scale of phenomenal proportions and they all greatly increase the mortality of morbidity rates for mothers and babies. Moreover, the effects of a pregnancy complicated by these conditions can last a lifetime. Offspring from pregnancies complicated by these conditions have increased risk of developing cardiovascular disease, diabetes or obesity in adult life.

It is estimated that $US41 billion of the developed world's annual direct healthcare costs can be attributed to the provision of antenatal care and treatment for major pregnancy complications. In the UK alone, £4 billion is spent annually on neonatal intensive care (levels 2 and 3) needed by babies born to women suffering from these diseases. The indirect costs in these in utero complications - for example, the healthcare associated with long-term illness, loss of education and parents' earnings/employment, and the provision of lifetime institutional care for children with severe disabilities - are enormous.

Currently, there are no effective interventions for these conditions. Consequently much of our work is aimed at identifying new diagnostic tools for predicting risk of developing complications, new treatments, including an MRC-funded programme on drug repurposing and new methods for specifically delivering therapies to placenta.

Fetal Growth Restriction (FGR)

FGR (fetal growth restriction) is a condition leading to a baby not growing to its full potential in the womb. It affects eight out of every hundred pregnancies and is associated with a dysfunctional placenta in more than 50% of cases.

Current projects in this area include:

  • Role of the fetoplacental endothelium in the attenuation of blood flow to the fetus during FGR: Brownbill, Sibley, Johnstone, Greenwood, Wareing
  • In vitro human placental perfusion studies to support the local administration of adenovirus-mediated VEGF gene therapy for the treatment of severe FGR: Brownbill, Sibley, Greenwood in collaboration with Dr Anna David, University College London
  • FGR: A failure of placenta adaptation in response to fetal nutrient demand? Dilworth
  • Development of novel nanocarriers for targeted delivery of drugs to placenta: Harris, Aplin, Cellesi, Tirelli
  • Microvascular placental imaging in FGR: Johnston, Aplin
  • Placental BOLD/OE MRI: Johnstone, Sibley
  • New ultrasound parameters in pregnancy: Johnstone
  • STRIDER: a multi-centre RCT examining the effects of Sidenafil on fetal growth: Johnstone in collaboration with Professor Zarko, Alfirevic, University of Liverpool
  • Elucidating potential therapies for FGR using mouse genetic models: Sibley, Greenwood, Wareing in collaboration with Professor Philip Baker, University of Auckland
  • IGF-II analogues as a novel placental therapy for FGR: Crocker, Westwood, Aplin, Sibley

 

We are currently recruiting to clinical studies in this area; see Research Clinics and Study Volunteers

Pre-eclampsia

Pre-eclampsia is a serious multi-system disorder of human pregnancy resulting in 70,000 maternal deaths worldwide. One in six stillbirths in the UK occur in pregnancies complicated by pre-eclampsia

Current projects in this area include:

  • Role of fetal haemoglobin in the aetiology of pre-eclampsia: Brownbill, Crocker in collaboration with Professor Stefan Hansson, University of Lund
  • Taurine transport proteins in the placenta: novel targets for correcting trophoblast cell turnover in pre-eclampsia? Desforges, Greenwood, Sibley
  • Pregnacy-specific glycoproteins in pre-eclampsia: Myers, Unwin
  • Prediction and prevention of adverse pregnancy outcomes in women with chronic hypertension: Myers
  • Comparison of different antihypertensive treatments in women with chronic hypertension in pregnancy: Myers in collaboration with Dr Lucy Chappell, King’s College London
  • Utility of PlGF in the diagnosis and management of pre-eclampsia: Myers
  • Development of novel nanocarriers for targeted delivery of drugs to placenta: Harris, Aplin, Cellesi, Tirelli
  • Elucidating potential therapies for pre-eclampsia using mouse genetic models: Sibley, Greenwood, Wareing in collaboration with Professor Philip Baker, University of Auckland

 

We are currently recruiting to clinical studies in this area; see Research Clinics and Study Volunteers

Premature labour

The final stage of pregnancy involves the co-ordination of powerful contractions of the uterus to deliver the baby and placenta successfully. Unfortunately in nearly one in 10 cases, these contractions occur too early in pregnancy and pre-term labour occurs.

Nearly three quarters of admissions to neonatal intensive care units are from babies born prematurely. Pre-term labour is the major obstetric problem influencing short- and long-term health. Its prevention and the treatment of established pre-term labour are inadequate. Rates of pre-term labour have not declined in the last 20 years.

We need to advance our understanding of the physiology of the uterus to improve our diagnosis and treatment of pre-term labour.

Current projects in this area include:

  • Blockade of decidual chemokines as a novel therapy for preterm labour: Jones, Harris, Tower, Stephens

Stillbirth

In the UK, stillbirth is defined as a baby born with no signs of life after 24 weeks of pregnancy. One in 200 pregnancies ends in stillbirth and these rates are not significantly different to those reported 20 years ago. Stillbirth has important medical, psychological, social and economic consequences. Women who experience a stillbirth are more likely to develop mental health problems, including depression, anxiety and post-traumatic stress disorder, which may impact on their families. Recent estimates suggest the annual cost of medical care for stillbirth is in excess of £20M; the social costs being much greater and extending to the wider family.

Research to develop preventative strategies is difficult as stillbirth is a multi-factorial problem and so requires a multi-disciplinary approach with roles for basic science, translational and health services research. Consequently, the Manchester Maternal and Fetal Health Research Centre is presently undertaking research in all three of these areas aiming to understand and prevent stillbirth, and improve care for parents who experience a stillbirth. We have an innovative clinical service, the Rainbow Clinic, to provide continuity of care from a stillbirth into a subsequent pregnancy, performing detailed placental assessments to identify any problems in subsequent pregnancies.

Current projects in this area include:

  • The Midlands and North of England Stillbirth Study (MiNoSS): Heazell
  • Outpatient assessment of fetal movements and fetal heart rate in women with reduced fetal movements or fetal growth restriction: Heazell, Fernando
  • Identifying placental function in pregnancies complicated by reduced fetal movement: Heazell, Johnstone, Higgins
  • Advanced Maternal Age: Identification of biochemical mechanisms underlying vulnerability to stillbirth:Jones, Heazell
  • Villitis of unknown etiology – unravelling placental dysfunction and causes of stillbirth: Heazell, Jones
  • Improving support for women in the next pregnancy following a stillbirth or neonatal death: Mills, Heazell
  • Undiagnosed Lupus-like autoimmunity and unexplained stillbirth: Crocker

Tackling pregnancy problems in the real world

We are also interested in understanding how real life , including maternal health problems such as diabetes and heart disease, and lifestyle factors (for example age, stress, obesity), affect pregnancy outcomes for both mother and child.

Diabetes is one of the most common complications of pregnancy, affecting between 3-5 per cent of pregnancies worldwide. An increasing number of women are presenting with pre-existing Type I and Type II diabetes. Others only develop diabetes during pregnancy (gestational diabetes). All forms of diabetes are associated with increased risks for both mother and baby. Mothers are more at risk of developing pre-eclampsia or other obstetric complications such as induction of labour and delivery by Caesarean section. Risks to the baby include congenital malformations, stillbirth and being born either too small or too large.

There is a growing trend amongst UK women to delay childbearing. In 2010, 20% of births in England and Wales were to women aged 35 years or over compared to just 6% in 1980.

This is a major clinical and public health concern because advanced maternal age is consistently associated with poor pregnancy outcome, particularly FGR, PTL and stillbirth, though it's not known why and how older mums have an increased risk.

Current projects in this area include:

  • The role of microRNAs in pregnancies complicated by maternal diabetes: Forbes, Aplin, Westwood
  • Utility of amniotic fluid erythropoietin in the management of pregnancies complicated by diabetes: Myers
  • New care pathways for the treatment of mild gestational diabetes: Myers in collaboration with Drs Denison (University of Edinburgh), Bugg (University of Nottingham) and Parsupathy (Kings College London)
  • Anti-coagulation therapy for women with prosthetic heart valves during pregnancy: Vause
  • Advanced maternal Age: identification of biochemical mechanisms underlying vulnerability to stillbirth: Jones, Heazell
  • The effect of coffee on maternal and placental vascular function: Wareing, Lavender

 

We are currently recruiting to clinical studies in this area; see Research Clinics and Study Volunteers