Antiplatelet therapy in pregnancy: A systematic review

Objective: To systematically review contemporary data on the safety of clopidogrel and newer antiplatelet agents in pregnant women, with particular attention to maternal and neonatal complications. Methods: The review protocol was published via PROSPERO (ID 42020165235) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Databases were searched using MeSH and free text terms encompassing the included antiplatelets, relevant indications, and pregnancy. Included studies reported the drug dose, the stage of pregnancy at which it was administered, and at least one primary or secondary outcome relating to pregnancy. The primary outcome was reporting of complications associated with antiplatelet use in pregnancy. Results: The search yielded 5271 results. 39 publications were included, incorporating 42 live births. The mean age of women was 34.6 years. Seven different antiplatelet agents were described, clopidogrel being most frequent (n = 37). 14 women received antiplatelet therapy in the first trimester. 14 women had regional anaesthesia (12 while taking clopidogrel), all without complication. Two women developed bleeding post caesarean section. There were no recorded neonatal delivery complications. Two neonates had congenital anomalies not felt to be related to maternal antiplatelet use. Conclusions: This systematic review describes outcomes for both mothers and neonates when exposed to clopidogrel at varying durations throughout gestation, and does not suggest higher than acceptable risk, with a congenital anomaly rate comparable to background risk. Evidence for other antiplatelet agents remains limited. Regional anaesthesia should be offered, with recommendation to stop prior to delivery in line with national guidance and in the context of individualised decision making.

Automated summary

This systematic review examines the safety of clopidogrel and newer antiplatelet agents in pregnant women, finding that there is no higher than acceptable risk for maternal and neonatal complications, with a congenital anomaly rate comparable to background risk. Evidence for other antiplatelet agents is limited. Regional anaesthesia is recommended, with advice to stop prior to delivery based on national guidance and individualized decision making.