Background: Around 3% of pregnancies in the UK are exposed to antidepressants, mostly in early pregnancy. These medications are not contraindicated during pregnancy, however there is still uncertainty around their safety for the developing fetus. Some studies have indicated a potential small increase in risk of pregnancy loss following exposure to antidepressants during pregnancy.
Objectives: To investigate the association between antidepressant exposure in trimester one and both miscarriage and stillbirth, using the UK Clinical Practice Research Datalink (CPRD).
Methods: CPRD is a repository of UK primary care data, with linkage to Hospital Episode Statistics (HES) secondary care data. We included women who were pregnant between 1996 and 2018 and had been diagnosed prior to their pregnancy with an indication for antidepressants (depression, anxiety or other (including migraine prophylaxis and stress incontinence)). We excluded pregnancies where the outcome was unknown (and unable to be ascertained from HES) or did not have sufficient follow up. We defined antidepressant use during trimester one as having at least one prescription of antidepressants overlapping with or starting between the pregnancy start date and trimester two. Exposed pregnancies were also split into prevalent users (at least one prescription in the 3 months before pregnancy) and incident users (no prescriptions in those 3 months). Miscarriage and stillbirth were defined in the Pregnancy Register or supplemented from HES where outcome was unknown. Multivariable Cox proportional hazards models were used to generate hazard ratios and 95% confidence intervals. Additional analyses are ongoing, including a propensity score analysis, exposure discordant pregnancy analysis, and multiple sensitivity analyses.
Results: Of the 127,826 eligible pregnancies diagnosed with an indication for antidepressants, 24,049 were exposed to antidepressants in trimester one. Among those with depression, antidepressant use was associated with a marginal increase in risk of miscarriage (aHR 1.06 95%CI 1.01–1.11). There was little evidence of an association between antidepressant use during trimester one and stillbirth for any indication. When comparing exposure to antidepressants among prevalent and incident users in trimester one, incident use appeared to be associated with a higher risk of miscarriage for depression and anxiety (aHR 1.23 95%CI 1.10–1.38 and aHR 1.25 95%CI 1.08–1.45, respectively). Results from the additional analyses will be presented.
Conclusions: The preliminary findings suggest that the risk of outcomes may be differential based on whether women were new initiators or already on antidepressants pre-pregnancy. The causal nature and meaning of these observations will be discussed.
