Foetal risk low in LMWH-exposed women during pregnancy

Pregnant women with preconception venous thromboembolism (VTE) who have no exposure to any anticoagulant and those on low-molecular-weight heparin (LMWH) have the lowest risk of foetal adverse outcomes, reveals a study, which supports the recommendation of LMWH during pregnancy.

“Few women in our cohort were exposed to non-vitamin K antagonist (VKA) oral anticoagulant (NOAC) during pregnancy, and the safety of NOACs during pregnancy cannot be substantiated with the current level of evidence,” the researchers said. “Thus, our study also serves as a call for future research on the benefits and harms of anticoagulation during pregnancy.”

Danish nationwide registries were used to identify all pregnant women with preconception VTE from 2000 to 2017 and linked data on exposure to LMWH, VKA, or NOAC during pregnancy. The researchers assessed pregnancy-related and foetal outcomes associated with first trimester anticoagulant exposure.

A total of 4,490 women were identified (mean age 31 years, 40-percent nulliparous), of whom 63.1 percent were unexposed, 25.9 percent were exposed to LMWH, 10.4 percent VKA, and 0.6 percent NOAC. Unexposed and LMWH-exposed women had the lowest risk of adverse outcomes. [Am J Med 2022;135:493-502.E5]

Compared with unexposed, VKA correlated with greater risks of preterm (adjusted odds ratio [aOR], 2.26, 95 percent confidence interval [CI], 1.70‒2.99) and very preterm birth (aOR, 3.78, 95 percent CI, 1.91‒7.49); shorter mean gestational age correlated with VKA (‒7.5 days, 95 percent CI, ‒9.1 to ‒5.9) or NOAC (‒2.3, 95 percent CI, ‒8.4 to 3.8); and lower mean birthweight was associated with VKA (‒55 g, 95 percent CI, ‒103.1 to ‒8.5) or NOAC (‒190 g, 95 percent CI, ‒364.1 to ‒16.4).

Among small for gestational age infants, the aORs were 1.07 (95 percent CI, 0.77‒1.50) with VKA and 3.29 (95 precent CI, 1.26‒7.95) with NOAC. Additionally, mean 5-minute Apgar score (9.8) and congenital defect prevalence (8.4‒10 percent) had little variation across exposure groups.

Of note, “[the] current knowledge of maternal and foetal risks of anticoagulation in pregnant women with preconception VTE is based on a relatively small number of observational studies that include limited numbers of pregnant women,” the researchers said.

Although several systematic and narrative reviews have been performed previously, they include the same small studies with very few data on foetal outcomes. [Blood 2005;106:401-407; J Thromb Haemost 2013;11:270-281]

Alternative treatment

The International Society for Thrombosis and Haemostasis (ISTH) recommends switching any NOAC treatment to an alternative anticoagulant prior to conception in women who want to be pregnant due to the potential for placental transfer and foetal toxicity. Specifically, ISTH recommends switching either to VKA or to LMWH. [J Thromb Haemost 2016;14:1673-1676]

“In accordance with this recommendation, in our cohort, NOAC was essentially not used following the first antenatal general practitioner pregnancy interview,” the researchers said.

“Importantly, our findings raise questions about the ISTH recommendation of preconceptionally switching from NOAC to VKA, because VKA exposure in early pregnancy was associated with higher risks of unfavourable pregnancy-related and foetal outcomes,” they added.