Patterns of prenatal antidepressant exposure and risk of preeclampsia and postpartum haemorrhage

Background Antidepressant use later in pregnancy has been associated with preeclampsia and postpartum haemorrhage (PPH) in some studies. Objectives To evaluate the association between patterns of prenatal antidepressant dose across gestationand risk of precclampsia and PPH. Methods We utilised OptumLabs (R) Data Warehouse (2012-2016) administrative health care claims, identifying 226 932 singleton liveborn deliveries for this retrospective cohort study. Antidepressant dispensing doses were converted to fluoxetine equivalents. Using k-means longitudinal, we identified women with similar patterns of antidepressant exposure, that is, trajectory groups, during the first 20 and 35 gestational weeks. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between trajectory groups and preeclampisa (20-week groups) and PPH (35-week groups), adjusting for demographics, co-morbidities, and other psychotropic medications. Linear trend tests assessing increasing risk of the outcomes across groups were performed. Results Among 15 041 (6.6%) pregnancies exposed to an antidepressant, the following trajectory groups were identified: A-low exposure, starting pregnancy at similar to 10 mg/d, with 1st trimester reduction/discontinuation, B-low sustained exposure of similar to 20 mg/d, C-moderate exposure (similar to 40 mg/d) with 1st trimester reduction/discontinuation, D-moderate sustained exposure of similar to 40 mg/d, and E-high sustained exposure of similar to 75 mg/d. In the low exposure with reduction/discontinuation trajectory, risks were 8.2% for preeclampsia and 2.7% for PPH. Compared with this group, low, moderate, and high sustained trajectories were associated with preeclampsia (adjusted RR 1.17, 95% CI 1.01, 1.34; RR 1.31, 95% CI 1.12, 1.54; and RR 1.41, 95% CI 1.05, 1.90, respectively) and PPH (RR 1.32, 95% CI 1.05, 1.66; RR 1.35, 95% CI 1.03, 1.78; RR 2.51, 95% CI 1.69, 3.71, respectively);P < .01 for linear trend tests for both outcomes. There was no increased risk for either outcome for moderate exposure with reduction/discontinuation (trajectory C). Conclusions Women with sustained antidepressant exposure, especially at higher doses, were at increased risk for preeclampsia and PPH, but underlying depression and anxiety may contribute to the increased risk.