OAA Large Project Grants

This proposal has been written in partnership with a mixed group of women with varied personal experiences of pregnancy and pregnancy complications, in accordance with INVOLVE guidelines on public and patient engagement.

Background: 200 in every 1000 women who choose to have an epidural to make their labour less painful develop a fever. If women develop a fever during labour, it prompts obstetric doctors to worry that there may be an infection causing the fever, which can cause problems for the baby. Our work suggests that the main drug used in epidurals may cause this fever, rather than infection. The drug used for epidurals is called bupivacaine. We think that the drug stops the body releasing an "anti-fever" protein called interleukin-1 receptor antagonist [ from circulating white blood cells. This protein is important as it suppresses fever in the body. In some women, the level of this protein is naturally low due to a genetic change in the IL-1Ra "anti-fever" gene. When these women are given an epidural with bupivacaine in it, they may be more likely to develop a fever. This might affect up to 30,000 women per year. Fever in labour is usually considered to be due to infection. Because of concern about fever in labour these women are more likely to have surgery to deliver their baby, and to receive antibiotics, when they may not need them. Antibiotics are associated with side effects in mothers and/or babies.
Aims: the project aims to identify women who may be genetically programmed to have a fever if they choose an epidural during labour. By identifying this group of women, we may be able to make their labours more comfortable and less stressful by knowing they have a higher chance of developing a fever.
Methodology: this is a laboratory and clinical study where we will measure the oral temperature of labouring women after their epidurals are started. We will also use blood or saliva samples to determine whether women have this specific gene change, which may predispose them to epidural fever. We will compare how many women get a fever after epidural in relation to their genetic differences for the "anti-fever" gene. We will also see whether alternative drugs that can be used in epidurals stop the anti-fever protein leaving white blood cells obtained from women in active labour before they receive their epidural for pain relief.
Expected outcomes: First, we will see if we can predict before labour those women who may develop fever after having an epidural in labour. Second, if we discover an alternative drug to bupivacaine that does not affect the release of the "anti-fever" protein from white blood cells, this will offer a sensible alternative pain killer to women who may be at increased risk of having a fever in labour if they choose to have an epidural with bupivacaine.
Implications: The practical implications of our study results will enable doctors and midwives to advise women about their best options for pain relief during labour.

Expectant mothers commonly require obstetric surgery. This may include: Caesarean Section (delivery of the baby through a cut in the lower abdomen); operative vaginal delivery (e.g. using forceps to help deliver the baby) and surgery after the baby is born (e.g. to repair a vaginal tear).

Most women requiring anaesthesia for obstetric surgery have an epidural or spinal anaesthetic (collectively known as neuraxial anaesthesia). These are injections in the back which are intended to completely numb the abdomen and pelvis, while the patient remains awake. We do not know how well neuraxial anaesthesia performs for obstetric surgery (defined as the need for additional pain relief or conversion to another form of anaesthesia). Nor do we know the variation in how anaesthetists manage failed neuraxial anaesthesia, and how or if this affects the mother in the short or longer term.

Our proposed programme of work contains 3 inter-related studies.

Study 1 is a survey of every NHS obstetric anaesthetic department, to help us learn about local guidance on how pain should be managed under neuraxial anaesthesia.

Study 2 is designed to estimate the rate and help understand reasons and risk factors for pain under neuraxial anaesthesia. We will ask anaesthetists to collect data on every patient having an obstetric operation which started under neuraxial anaesthesia for a period of 4 weeks in every participating NHS hospital. We will collect information about the patient, the circumstances (e.g. if it was a planned or emergency operation) and the care provided.

In Study 3, on the day after surgery, we will seek consent from women who had an obstetric operation which started under neuraxial anaesthesia to complete two questionnaires - one the day after surgery, and one 6 weeks later. The first questionnaire will ask about women's experiences of the procedure and their short-term recovery (e.g., when they were able to walk about, feed their baby and go to the toilet). For women who felt pain or discomfort during their procedure, we will ask about how effective additional pain relief was, and explore how communication was with the anaesthetist and broader obstetric team. The 6-week questionnaire will ask about symptoms of post-natal depression and post-traumatic stress. We will compare the responses of women who did and did not have pain or discomfort during their procedure, and compare responses based on characteristics of the mother (e.g. age, health) and of the operation (e.g. the type of operation and anaesthetic technique).

Our team includes international experts in large-scale research and in obstetric anaesthesia. We plan to include patient representation in every stage of the design and delivery of the study. At the end of this project, we will be able to define how often pain occurs in obstetric surgery, understand any risk factors for this happening, and what the longer-term implications are for new mothers. This will allow us to address this important issue in future research, and provide better information for future patients, their families and the doctors and midwives who care for them.