Antidepressant use during pregnancy and the risk of preterm birth – a cohort study

Major depressive disorder and exposure to antidepressants during pregnancy have been previously associated with preterm birth (PTB). However, the reported results are inconsistent. In this study, we aimed to estimate the effects of antidepressants and maternal depression on the risk of PTB using data from electronic health records (EHRs). This is a population-based retrospective cohort study, utilizing data from primary care EHRs. The cohort included 216,070 deliveries of 176,866 patients from the UK between January 1996 and February 2019. We analyzed the effects of antidepressant exposure during pregnancy on the risk of PTB and additional control outcomes in subgroups of patients with a history of depression, and with recent pre-pregnancy treatment. We also assessed the effect of depression alone, in untreated patients. The analysis utilized large-scale propensity score matching that included all demographic and clinical covariates, and effect estimation using a Cox model. The main cohort included 17,615 (8.2%) PTBs. Among patients who were not exposed to antidepressants during pregnancy, a history of depression was associated with an increased risk of PTB (HR 1.10, CI [1.04,1.15], P < 0.01]. Patients exposed to SSRIs during the first 22 weeks of gestation were not at a significantly higher risk of PTB compared to unexposed patients (HR 1.08 CI [0.98,1.18], P = 0.11). Moreover, treatment continuation during pregnancy did not affect the risk of PTB among patients with pre-pregnancy treatment (HR 1.03 CI [0.92,1.15], P = 0.61), and among patients with a history of depression (HR 1.00 CI [0.90,1.11], P = 0.98). Additionally, exposure to antidepressants was associated with a reduced risk of some common medical conditions during the outcome follow-up period. Our findings indicate that the concern of PTB should not affect the clinical decision of medical treatment for pregnant women suffering from depression, since antidepressant treatment by itself does not increase the risk of PTB.