Department of Cardiology, Aalborg University Hospital, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark.
Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark; Unit for Clinical Biostatistics, Aalborg University Hospital, Denmark.
Am J Med. 2022 Apr;135(4):493-502.e5. doi: 10.1016/j.amjmed.2021.10.023. Epub 2021 Nov 17.
The purpose of this study was to investigate first trimester anticoagulant exposure and risks of adverse pregnancy-related and fetal outcomes.
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.
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.
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.
本研究旨在探讨妊娠早期抗凝药物暴露与不良妊娠相关和胎儿结局的关系。
我们利用丹麦全国性登记处，确定了 2000 年至 2017 年间所有患有孕前静脉血栓栓塞症的孕妇，并对妊娠期间低分子肝素（LMWH）、维生素 K 拮抗剂（VKA）或非 VKA 口服抗凝剂（NOAC）的暴露情况进行了数据关联。我们评估了与妊娠早期抗凝药物暴露相关的妊娠相关和胎儿结局。
在 4490 例患有孕前静脉血栓栓塞症的孕妇（平均年龄 31 岁，40%为初产妇）的妊娠早期，63.1%未暴露，25.9%暴露于 LMWH，10.4%暴露于 VKA，0.6%暴露于 NOAC。未暴露和 LMWH 暴露组的不良结局最低。与未暴露组相比，VKA 与早产（校正优势比 [OR] 2.26；95%置信区间 [CI]，1.70-2.99）和极早产（校正 OR 3.78；95% CI，1.91-7.49）的风险更高相关，VKA 与较短的平均胎龄相关（-7.5 天；95% CI，-9.1 至-5.9 天）或 NOAC（-2.3 天；95% CI，-8.4 至 3.8 天），VKA 与较低的平均出生体重相关（-55 克；95% CI，-103.1 至-8.5）或 NOAC（-190 克；95% CI，-364.1 至-16.4）。VKA 的小胎龄儿校正 OR 为 1.07（95% CI，0.77-1.50），NOAC 的校正 OR 为 3.29（95% CI，1.26-7.95）。各组的平均 5 分钟 Apgar 评分（9.8）和先天性缺陷发生率（8.4%-10%）差异不大。
未暴露和 LMWH 暴露组的胎儿风险最低，支持妊娠期间使用 LMWH。由于 NOAC 暴露的罕见性，NOAC 在妊娠期间的安全性尚不清楚。
