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Thromb Haemost 2017; 117(05): 870-879
DOI: 10.1160/TH16-11-0838
Coagulation and Fibrinolysis
Schattauer GmbH

Pregnancy outcome of first trimester exposure to the vitamin K antagonist phenprocoumon depends on duration of treatment

Eleanor Hüttel
1   Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité - Universitätsmedizin Berlin, Germany
,
Stephanie Padberg
1   Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité - Universitätsmedizin Berlin, Germany
,
Reinhard Meister
2   Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences), Berlin, Germany
,
Evelin Beck   *
1   Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité - Universitätsmedizin Berlin, Germany
,
Christof Schaefer   *
1   Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité - Universitätsmedizin Berlin, Germany
› Author Affiliations Financial support: This work was supported by the German Federal Institute for Drugs and Medical Devices (BfArM). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Further Information

Publication History

Received: 07 November 2016

Accepted after major revision: 02 February 2017

Publication Date:
28 November 2017 (online)

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Summary

The aim of this observational cohort study was to specify the risk of the vitamin K antagonist (VKA) phenprocoumon during first trimester of pregnancy, in particular to estimate the risk of birth defects and spontaneous fetal loss. Four hundred eight pregnancies with phenprocoumon exposure were compared to 1,642 pregnancies neither exposed to VKA nor to other major teratogens or fetotoxicants. There was no typical warfarin embryopathy in our exposed cohort. However, the overall rate of major birth defects was significantly increased (7.4 % vs 2.3 %; adjusted odds ratio [ORadj] 2.14; 95 % confidence interval [CI] 1.4–3.4). With early cessation until five completed gestational weeks the birth defect risk was similar to the comparison cohort (2.4 % vs 2.3 %; ORadj 1.07; 95 % CI 0.2–3.6). With treatment duration exceeding seven gestational weeks the rate of major birth defects increased up to five-fold (10.8 % vs 2.3 %; ORadj 5.18; 95 % CI 2.0–11.6). The overall risk of spontaneous abortion (SAB) was 38.0 % vs 17.5 % in the comparison cohort (adjusted hazard ratio [HRadj] 2.9; 95 % CI 2.2–3.9). The treatment duration had a significant effect on the hazard of SAB (HRadj 1.12; 95 % CI 1.01–1.25 per each additional exposure week). Phenprocoumon and other VKA carry an embryotoxic risk. This risk seems to be time-dependent with a steep risk increase for birth defects and also for fetal loss after week 5. If maternal disease permits, VKA therapy should be switched to safer alternatives such as heparins immediately after early recognition of pregnancy.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Time-dependence - spontaneous abortion - congenital malformation - thrombosis prophylaxis - observational cohort study

* Both authors contributed equally to this article.


 

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