Pharmacoepidemiology in pregnancy: analysis protocol for an observational cohort study in the UK Clinical Practice Research Datalink.

Large numbers of women take prescription and over-the-counter medications during pregnancy. However, there is very little definitive evidence about the potential effects of these drugs on the mothers and offspring. We will investigate the risks and benefits of continuing prescriptive drug use for chronic pre-existing maternal conditions such as diabetes, hypertension and thyroid related conditions throughout pregnancy. If left untreated, these conditions are established risk factors for adverse neonatal and maternal outcomes. However, some treatments for these conditions are associated with adverse neonatal outcomes. Our primary aims are twofold. Firstly, we aim to estimate the beneficial effect on the mother of continuing treatment during pregnancy. Second, we aim to determine whether there is an associated detrimental impact on the neonate of continuation of maternal treatment during pregnancy. To establish this evidence, we will investigate the relationship between maternal drug prescriptions and adverse and beneficial offspring outcomes to provide evidence to guide clinical decisions. We will conduct a hypothesis testing observational intergenerational cohort study using data from the UK Clinical Practice Research Datalink (CPRD). We will apply four statistical methods: multivariable adjusted regression, propensity score regression, instrumental variables analysis and negative control analysis. These methods should account for potential confounding when estimating the association between the drug exposure and maternal or neonatal outcome. In this protocol we describe the aims, motivation, study design, cohort and statistical analyses of our study to aid reproducibility and transparency within research.