Reproductive safety of direct oral anticoagulants after maternal exposure in early pregnancy: a comparative ENTIS cohort study.

OBJECTIVES

Direct oral anticoagulants (DOAC) are increasingly prescribed to women of childbearing age, making inadvertent first-trimester exposure more likely. We prospectively evaluated the risks of major birth defects and pregnancy loss following first-trimester DOAC exposure.

DESIGN

We conducted a multicenter, observational prospective cohort study comparing pregnancy outcomes in women exposed to a DOAC during the first trimester of pregnancy and a reference group of women exposed to a low molecular weight heparin (LMWH) during the first trimester, between 2008 and 2024.

RESULTS

A total of 343 DOAC-exposed and 698 LMWH-exposed pregnancies were included. DOAC exposure was not associated with an increased risk of major birth defects (DOAC n=8/279, 2.9%; LMWH n=25/586, 4.3%; adjusted OR 0.74, 95%CI 0.33-1.67). In the cumulative incidence analysis (340 DOAC; 688 LMWH), the rates of live birth, pregnancy loss, and pregnancy termination were 73%, 13% and 14% in the DOAC group, and 75%, 20% and 5% in the LMWH reference group. Cox-proportional cause-specific hazard models indicated no increased risks for pregnancy loss after DOAC exposure, but a higher hazard of pregnancy termination.

CONCLUSIONS

First-trimester DOAC exposure was not associated with a substantially increased risk of major birth defects or pregnancy loss, and the observed defects did not suggest a teratogenic pattern, consistent with reported findings in the existing literature. These results offer further reassurance for counselling in case of inadvertent exposure. Larger studies are still warranted to validate these findings due to a limited sample size and window of exposure.