Time trends in antithrombotic therapy during pregnancy and maternal and perinatal outcomes in the Netherlands (2013–19): a nationwide cohort study

Background: Considering the paucity of data, we aimed to describe nationwide time trends in antithrombotic therapy during pregnancy and risks of maternal and perinatal outcomes in the Netherlands. Methods: In this nationwide cohort study, all female individuals aged 16–45 years with delivery records in the Dutch perinatal registry between Jan 1, 2013, and Dec 31, 2019, and their infants, were included. Individually linked data from Statistics Netherlands on outpatient medication prescriptions, in-hospital diagnoses, and mortality were used to evaluate time trends in antithrombotic therapy during pregnancy, and risks of maternal and perinatal outcomes (including thromboembolism, bleeding, preeclampsia and eclampsia, and low birthweight). Findings: A total of 1 122 711 pregnancies and 1 139 116 infants were included (median maternal age 30·5 years [IQR 27·3–33·7]; 886 085 [78·9%] White; median gravidity 2 (IQR 1–3); and median gestational age at delivery 39 weeks [IQR 38–40]). Low-molecular-weight heparin (LMWH) was the most commonly (more than 99%) prescribed anticoagulants during pregnancy, which slightly increased from 0·7% (1063 of 163 479) in 2013 to 0·9% (1352 of 158 654) in 2019. LMWH was generally started at 5–8 weeks’ gestation when oral anticoagulant prescriptions dropped. Antiplatelet drug prescriptions increased from 0·7% (1129 of 163 479) to 4·8% (7671 of 158 654), which primarily initiated around week 12. Maternal risks of venous and arterial thromboembolism and bleeding remained constant from 2013 to 2019; the risk of preeclampsia and eclampsia gradually increased from 1·70% (95% CI 1·63–1·76) in 2013 to 2·05% (1·98–2·13) in 2017, after which it decreased to 1·83% (1·77–1·90) in 2019. There was a significant decrease (2019 vs 2013) in low birthweight (adjusted odds ratio 0·92 [0·90–0·94]; p<0·0001), whereas 28-day neonatal bleeding risk remained unchanged. Interpretation: Exposure to anticoagulants during pregnancy is not uncommon, and health-care providers and female individuals of reproductive age should be mindful of this to avoid unintended oral anticoagulant exposure. Adhering to guidelines for aspirin use to prevent preeclampsia might lead to a population-level reduction in disease burden and potential improvement in neonatal prognosis. Funding: None. Translation: For the Dutch translation of the abstract see Supplementary Materials section.