For most mothers pregnancy is a safe and straightforward process but for 1 in 5 unexpected complications can occur and are a major cause of childhood disability. Our research team at the University of Leeds, headed by Mr Nigel Simpson, focuses on understanding the causes of these complications and aims to predict and stop them from happening.
In this article Mr Simpson explains his journey into research.
“Maternity is a fast-paced, exciting, highly rewarding place to work in. When I started as a junior doctor I quickly recognised that once labour started safe delivery of the baby was my priority, but many other issues appeared beyond my control. These arose in three areas: when delivery came too soon (preterm or premature birth), when the size of the baby was less than expected (low birthweight), and when the mother had life-threatening high blood pressure (also known as pre-eclampsia). In all, 1 in 5 first-time mums encountered one of these three problems. The factors causing these complications were poorly understood and usually appeared unchangeable, with no therapies available to prevent them happening.
When I subsequently worked for six months within a neonatal unit I then saw the short and long term consequences for these babies and their families, in particular the likelihood of brain injury. It struck me at that time that our responsibilities for the mother and baby in pregnancy needed to extend to the prediction and prevention of these adverse outcomes rather than to simply react to their happening.
During my training I applied for a research post in Canada and spent two years investigating the monitoring of babies’ well-being in pregnancy (ie how we could make sure they were well before and during labour, and when we should prepare for a planned birth) and also the development of the placenta (afterbirth) in early pregnancy, and recognised that events occurring early on in pregnancy would be an important predictor of well-being later.
When I returned to the UK I then began to focus on the prediction and prevention of these complications. At the centre of my work were the links between research, teaching, and clinical practice, and the importance of each informing the other. In the research field, automated analytic technology, the sequencing of the human genome, and improved computational power offered major opportunities for progress but required collaboration with funders and the participation of expectant mums in order to acquire the large numbers of samples required to prove that the potential breakthroughs from smaller, laboratory-based projects were applicable in the clinical situation.
Cerebra’s sponsorship ensured that we were able to contribute to the world’s largest pregnancy biobank (SCOPE), in which seven maternity centres asked first time mums in early pregnancy if they were willing to give a small blood sample along with lifestyle information, and then for researchers to collect information about how the pregnancy had progressed. We successfully followed over 5500 mums in this way. The samples collected have given an invaluable insight into the factors that can predict pregnancy complications. The paper which we then published in 2014 was selected as the top clinical science paper that year by the journal Hypertension. This work, together with further national clinical studies we were involved in studying mums later in pregnancy, led to the identification of a biomarker called placental growth factor (PlGF) as being highly predictive for early delivery of the baby in at-risk mums. Its use in routine clinical practice is currently being evaluated by NICE, and should make sure that doctors and midwives are more able to accurately identify mums needing additional support whilst at the same time reassuring others who are not actually at additional risk. We have also just completed a five-year global study investigating the genetic basis for pre-eclampsia, and it is again likely that these findings will form the basis of future predictive tests and enlarge our understanding of factors causing conditions like pre-eclampsia.
Throughout these long-term studies, in the laboratory we have also been investigating the mechanisms causing these complications. In conjunction with researchers from Harvard we have been able to begin to unpick the inflammatory pathways causing preterm birth using new methods of analysing large and complex datasets – a new field called bioinformatics or systems biology. This will give a better understanding of further predictive tests as well as the best approaches to prevent preterm birth.
One of our PhD students is studying the make up of the cervix (neck of the womb) and how this alters in mums more likely to deliver early. This work fits in nicely with a national study we are part of which is trying to determine which type of suture material we should use to reinforce the cervix to prevent it happening in these mums (C-STICH). These studies were highlighted in a recent NIHR online course which explained the importance of clinical research studies. One of our other PhD students, using unique digital imaging techniques pioneered here in Leeds, has been understanding the mechanisms causing the placenta to fail in pregnancy and lead to later problems like low birthweight babies.
In addition to these large international studies we have continued to look carefully at our local mums to understand how lifestyle can affect pregnancy outcome. Unsurprisingly, it is clear that a balanced diet, together with healthy lifestyle and regular midwife visits are very important for healthy outcomes – although not totally protective for all complications.
All of this knowledge and experience helps us deliver more effective care for the mums coming through our maternity unit. Leeds was one of the first hospitals in the country to set up a preterm birth prevention clinic, which now looks after over 300 at-risk mums each year. Our rate of preterm birth has fallen in Leeds (in distinction to national and international trends), and we have been encouraging the development of other clinics in different UK cities through a national network, offering training, research, and practical advice to clinicians and midwives.
Working in partnership with Cerebra has helped us achieve these goals, and we trust, will help us achieve more in the years to come”.
Mr Nigel Simpson is a Consultant Obstetrician and Gynaecologist at the Leeds Teaching Hospital NHS Trust and Associate Professor at the University of Leeds. He is also a National Lead for the NIHR Clinical Research Network
for Reproductive Health & Childbirth.
You can find out more about the work of our Leeds research team here.