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

Abstract

Abstract Background Major depressive disorder and exposure to antidepressants during pregnancy have been previously associated with preterm birth (PTB). However, the reported results are difficult to interpret due to the inherent confounding by indication bias. We aimed to estimate the disentangled effects of antidepressants and maternal depression on the risk of PTB using data from electronic health records (EHRs). Methods This is a population-based retrospective cohort study, utilizing data from a primary care EHR. The cohort included 216,070 deliveries of 176,866 patients from the United Kingdom between January 1996 and February 2019. We analyzed the effects of antidepressant exposure, in particular selective serotonin reuptake inhibitors (SSRI), 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 a subgroup of untreated patients. The analysis utilized large-scale propensity score matching that included all demographic and clinical covariates (conditions, drug prescriptions, observations, and procedures), and effect estimation using a Cox model. Results The main cohort included 17,615 (8.2%) PTBs of 16,946 mothers. 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 at a marginally higher risk of PTB (during weeks 23 to 37) compared to unexposed patients (HR 1.08, CI [0.98,1.18], P = 0.11). However, subgroup analysis demonstrated that among patients with pre-pregnancy use of SSRIs, treatment continuation during pregnancy did not affect the risk of PTB (HR 1.03 [0.92,1.15], P = 0.61), as well as among patients with history of depression (HR 1.00 [0.90,1.11], P = 0.98). Additionally, in these subgroups exposure to antidepressants was associated with a reduced risk of some common medical conditions during the PTB follow-up window. These conditions, which are otherwise increased by depression, included upper respiratory infection, constipation, and headache. Conclusion Depression is associated with a higher risk of PTB, while exposure to antidepressants during pregnancy does not affect the observed risk. The clinical decision regarding antidepressant treatment during pregnancy should therefore consider the patient-specific risk-benefit potential, regardless of the concern of PTB.