First trimester antidepressant use and miscarriage: a comprehensive analysis in the UK Clinical Practice Research Datalink

ObjectivesTo investigate the risk of miscarriage associated with first trimester antidepressant use. DesignPopulation-based cohort study. SettingUK Clinical Practice Research Datalink (CPRD) GOLD. Participants661 825 individuals who had 1 021 384 pregnancies in CPRD GOLD between 1996 and 2018. Main outcome measuresMiscarriage defined as a pregnancy loss prior to 24 weeks gestation. ResultsAmong the eligible pregnancies, 73 540 were prescribed antidepressants in trimester one (7.2%); 14.7% antidepressant prescribed pregnancies ended in miscarriage, as opposed to 12.4% of those not prescribed antidepressants. Antidepressant use during trimester one was associated with miscarriage in the unadjusted models (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.19 to 1.23), which attenuated following adjustment for covariates (aHR 1.04, 95% CI 1.02 to 1.06). These findings translated to an absolute risk adjusted for confounders of 13.1% (95% CI 13.0 to 13.2) in the unexposed compared to 13.6% (95% CI 13.3 to 13.8) in the first trimester antidepressant exposed. The propensity score matched model showed similar results (aHR 1.09, 95% CI 1.02 to 1.17, respectively). In those with depression or anxiety in the 12 months before pregnancy, our estimate didnt change (aHR 1.04, 95% CI 1.01 to 1.08). ConclusionFirst trimester antidepressant use was associated with a small yet clinically insignificant increase in risk of miscarriage, with no evidence suggesting taking antidepressants before pregnancy and into first trimester increases the risk of miscarriage. The conclusions are less clear for incident antidepressant use in trimester one, however issues including gestational dating in early pregnancy and probable residual confounding prohibit us from interpreting this observation as causal.