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® 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 ~10 mg/d, with 1st trimester reduction/discontinuation, B-low sustained exposure of ~20 mg/d, C-moderate exposure (~40 mg/d) with 1st trimester reduction/discontinuation, D-moderate sustained exposure of ~40 mg/d, and E-high sustained exposure of ~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.
(© 2020 John Wiley & Sons Ltd.)