First Trimester Anticoagulant Exposure and Adverse Pregnancy Outcomes in Women with Preconception Venous Thromboembolism: A Nationwide Cohort Study

Am J Med. 2022 Apr;135(4):493-502.e5. doi: 10.1016/j.amjmed.2021.10.023. Epub 2021 Nov 17.

Abstract

Objective: The purpose of this study was to investigate first trimester anticoagulant exposure and risks of adverse pregnancy-related and fetal outcomes.

Methods: Using 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.

Results: Among 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.

Conclusions: Fetal 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.

Keywords: Anticoagulant drug safety; Low-molecular-weight heparin; Non-VKA oral anticoagulant; Pregnancy; Thromboembolic complications; Vitamin K antagonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants / adverse effects
  • Cohort Studies
  • Female
  • Heparin, Low-Molecular-Weight / adverse effects
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, First
  • Premature Birth* / chemically induced
  • Premature Birth* / epidemiology
  • Venous Thromboembolism* / chemically induced
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / epidemiology
  • Vitamin K

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Vitamin K