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- Mette Søgaard, Flemming Skjøth, Peter Brønnum Nielsen, Jan Beyer-Westendorf, and Torben Bjerregaard Larsen.
- Department of Cardiology, Aalborg University Hospital, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark. Electronic address: mette.soegaard@rn.dk.
- Am. J. Med. 2022 Apr 1; 135 (4): 493-502.e5.
ObjectiveThe purpose of this study was to investigate first trimester anticoagulant exposure and risks of adverse pregnancy-related and fetal outcomes.MethodsUsing Danish nationwide registries, we identified all pregnant women with preconception venous thromboembolism, 2000-2017, and linked data on exposure to low-molecular-weight heparin (LMWH), vitamin K antagonist (VKA), or non-VKA oral anticoagulant (NOAC) during pregnancy. We assessed pregnancy-related and fetal outcomes associated with first trimester anticoagulant exposure.ResultsAmong 4490 pregnancies in women with preconception venous thromboembolism (mean age 31 years, 40% nulliparous) during the first trimester, 63.1% were unexposed, 25.9% were exposed to LMWH, 10.4% VKA, and 0.6% NOAC. Adverse outcomes were lowest in unexposed and LMWH exposed. Compared with unexposed, VKA was associated with higher risks of preterm (adjusted odds ratio [OR] 2.26; 95% confidence interval [CI], 1.70-2.99) and very preterm birth (adjusted OR 3.78; 95% CI, 1.91-7.49), shorter mean gestational age was associated with VKA (-7.5 days; 95% CI, -9.1 to -5.9 days) or NOAC (-2.3 days; 95% CI, -8.4-3.8), and lower mean birthweight with VKA (-55 g; 95% CI, -103.1 to -8.5) or NOAC (-190 g; 95% CI, -364.1 to -16.4). Adjusted ORs for small-for-gestational-age infants were 1.07 (95% CI, 0.77-1.50) with VKA, and 3.29 (95% CI, 1.26-7.95) with NOAC. Mean 5-minute Apgar score (9.8) and congenital defect prevalence (8.4%-10%) varied little across exposure groups.ConclusionsFetal risk was lowest in unexposed and LMWH-exposed pregnancies, supporting the recommendation of LMWH during pregnancy. NOAC safety during pregnancy is unclear due to the rarity of NOAC exposure.Copyright © 2021 Elsevier Inc. All rights reserved.
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