TY - JOUR
T1 - First trimester anticoagulant exposure and adverse pregnancy outcomes in women with preconception venous thromboembolism
T2 - a nationwide cohort study
AU - Søgaard, Mette
AU - Skjøth, Flemming
AU - Nielsen, Peter Brønnum
AU - Beyer-Westendorf, Jan
AU - Larsen, Torben Bjerregaard
N1 - Copyright © 2021 Elsevier Inc. All rights reserved.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
KW - Anticoagulant drug safety
KW - Low-molecular-weight heparin
KW - Non-VKA oral anticoagulant
KW - Pregnancy
KW - Thromboembolic complications
KW - Vitamin K antagonist
UR - http://www.scopus.com/inward/record.url?scp=85127317336&partnerID=8YFLogxK
U2 - 10.1016/j.amjmed.2021.10.023
DO - 10.1016/j.amjmed.2021.10.023
M3 - Journal article
C2 - 34798098
SN - 0002-9343
VL - 135
SP - 493-502.E5
JO - The American Journal of Medicine
JF - The American Journal of Medicine
IS - 4
ER -