Medicines prescribed in pregnancy: Protocol for a signal detection study using routinely collected data in England

Medication use in pregnancy is common and increasing. Pregnant women are often excluded from drug trials, therefore the safety to mother and baby of many medications used in pregnancy is unknown. Routine health data have been used to look for evidence of harm and safety of specific medications, but not to systematically look across all prescribed medications in pregnancy.

To systematically identify medications prescribed during pregnancy requiring further research into their potential harms to mother or baby.

We will describe trends in primary care prescribing in pregnancy over time, and socio-demographic patterning of prescribing, using data from pregnancies in the Clinical Practice Research Datalink (CPRD). We will identify and categorise maternal, fetal, and infant adverse outcomes reported in the CPRD and linked hospital and mortality data. We will use Bayesian signal detection models to analyse all medication/outcome pairs to identify where an outcome occurs significantly more frequently in mothers prescribed a specific medication than in mothers not prescribed it. Potential confounders will not be accounted for at this stage. Published evidence on the identified medication/outcome pairs will be reviewed and incorporated with the results from trends and signal detection analyses. These data will be used by Patient Involvement and Study Advisory Board workshops to prioritise medications for further research, with medications more commonly prescribed for underserved groups being given precedence. For three prioritised signals, cohort analyses will compare the occurrence of adverse outcomes in those prescribed compared to those not prescribed the medication of interest, adjusting for maternal morbidity, co-medications, and other measured confounders.

This project will provide a list of medications used in pregnancy that should be prioritised for further safety research. Results of three detailed retrospective cohort studies will contribute to informed decision making for patients and clinicians. Study grant number: NIHR207172; CPRD accepted protocol number: 24_004518.