Between 2020 and 2022 in the United Kingdom (UK), there were 45 maternal deaths from venous thromboembolism (VTE), out of more than 2 million maternities. This occurred despite extensive risk assessment and prescribing of low molecular weight heparin (LMWH) thromboprophylaxis, alongside clinicians' overestimate of risk and commitment to the cause. Whilst every maternal death is a tragedy, the challenge ahead is immense—to identify, in an efficient and consistent way, those few women at risk of life‐threatening thrombosis, and then minimise that risk with a cost‐effective therapy that is acceptable to pregnant and postpartum women, and does not do more harm than good. We propose a way forward.

Women who are pregnant or in the postpartum period have a fourfold to fivefold increased risk of thromboembolism compared with nonpregnant women (1, 2). Approximately 80% of thromboembolic events in pregnancy are venous (3), with a prevalence of 0.5–2.0 per 1,000 pregnant women (4–9). Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the United States, accounting for 9.3% of all maternal deaths (10).

To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).Randomised controlled trial.Specialist clinic for recurrent miscarriages.90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation.Rate of live births with the two treatments.There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%).Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.

This study aimed to investigate the reporting association between aspirin use and pregnancy-related adverse events (AEs), and to explore potential disproportionality signals for congenital disorders. A disproportionality analysis was performed using the Food and Drug Administration Adverse Event Reporting System data from Q1 2004 to Q3 2024. Four statistical approaches were applied: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean (EBGM). In addition, 2 sensitivity analyses were performed to verify the robustness of the results by excluding certain confounders. The analysis identified 1647 reports documenting aspirin-associated AEs related to pregnancy and congenital disorders. Eighty-nine high-level term signals were detected, including 19 significant disproportionality signals, with the strongest signals in each category being “fetal growth complications” (n = 139, ROR = 9.89, PRR = 9.88, EBGM = 9.67, information component = 3.27) and “vascular anomalies congenital NEC” (n = 282, ROR = 39.68, PRR = 39.6, EBGM = 36.10, information component = 5.17). At the preferred term level, 269 signals were identified, with 47 significant disproportionality signals. The strongest signals in their respective categories were peripartum hemorrhage (n = 3, ROR = 41.11) and cyclopia (n = 5, ROR = 662.32). Sensitivity analyses, including adjustments for healthcare professional reports and the exclusion of patients with hypertension or gestational hypertension, confirmed the robustness of these signals. In conclusion, this large-scale pharmacovigilance study identified significant disproportionality signals for several pregnancy-related AEs and congenital disorders reported with aspirin use. While these findings provide preliminary signals for further investigation, they cannot establish causality. Clinical decisions should continue to be guided by established guidelines and evidence from randomized controlled trials.