First trimester antidepressant use and miscarriage: a population-based cohort study using Clinical Practice Research...

Depression and anxiety during pregnancy is on the rise, thus more pregnant women are being offered antidepressants; however, uncertainties remain surrounding safety.

To investigate the association between first trimester antidepressant use and miscarriage.

Population-based cohort study using the UK Clinical Practice Research Datalink (CPRD) GOLD.

Pregnancies included in the CPRD GOLD Pregnancy Register between 1996 and 2018 were identified. Pregnancies in those with prescriptions for antidepressants overlapping with the first trimester were defined as 'exposed' and compared with pregnancies in those who were unexposed. Cox models, adjusted hazard ratios (aHRs), and absolute risk of miscarriage were calculated adjusted for confounders including depression, anxiety, smoking, and other health, lifestyle, and obstetric factors.

Among the 1 021 384 eligible pregnancies, 73 540 patients were prescribed antidepressants in the first trimester (7.2%); 10 693/73 540 (14.5%) pregnancies ended in miscarriage among those prescribed antidepressants versus 116 641/947 844 (12.3%) in those not prescribed antidepressants. Antidepressant prescription during the first trimester was only modestly associated with miscarriage following adjustment (aHR 1.04, 95% confidence interval [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) for those not prescribed and 13.6% (95% CI = 13.3 to 13.8) for those prescribed antidepressants. Among those prescribed antidepressants in the 3 months before pregnancy and during the first trimester, the risk of miscarriage was the same as among those unexposed (aHR 1.00, 95% CI = 0.98 to 1.03).

First trimester antidepressant use was associated with a small, clinically insignificant increased risk of miscarriage, with no evidence suggesting taking antidepressants before pregnancy and into the first trimester increases the risk of miscarriage.