Autoimmune conditions affect around 13% of women in the UK (1) and are often diagnosed during their potentially reproductive years, including conditions like multiple sclerosis and rheumatoid arthritis. These conditions can be managed using monoclonal antibodies, a relatively new category of drug which has grown rapidly over the past two decades and are tailor-made to bind to particular protein targets.

Randomised clinical trials provide the gold-standard of evidence on how effective and how safe drugs are, but since pregnant participants are typically excluded from these trials, there is often a lack of evidence available for clinicians and doctors on how well drugs work and how safe they are for pregnant patients. This is the case for monoclonal antibodies, and particularly since many of these drugs have been developed very recently there is also limited evidence on their safety from observational studies which follow participant’s pregnancies over time. The limited evidence is particularly challenging since having an unmanaged autoimmune condition can increase your risk of an adverse pregnancy outcome, for instance inflammatory bowel disease is linked to increased risk of early pregnancy loss (2).

This project aims to understand how underlying autoimmune conditions and using monoclonal antibodies to treat them may cause adverse pregnancy events such as pregnancy loss, low birth weight, and pre-term birth, by examining natural genetic variation between participants within existing databases including ALSPAC.

First, the genetic variation associated with seven common autoimmune conditions will be used to assess if differences in participant’s genetic predisposition to an autoimmune condition may have a causal effect on adverse pregnancy outcomes. Second, to mimic how monoclonal antibodies work, the same method will be used but this time taking advantage of genetic variation in protein levels in blood to mimic the effects of these drugs which each target very specific proteins involved in the immune response. The project will assess whether variation in these proteins has a causal effect on adverse pregnancy outcomes, to provide evidence on whether monoclonal antibody drugs are safe to be used by pregnant patients to manage their autoimmune conditions.

1. Conrad, N. et al. (2023) ‘Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK’, The Lancet, 401(10391), pp. 1878–1890. Available at: https://doi.org/10.1016/S0140-6736(23)00457-9.
2. Nielsen, O.H. et al. (2022) ‘Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis’, Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 20(1), pp. 74-87.e3. Available at: https://doi.org/10.1016/j.cgh.2020.09.021.