Preeclampsia is characterized by maternal hypertension and end organ injury and affects 3% to 8% of pregnancies. It is a significant contributor to global maternal and neonatal morbidity and mortality.1 Aspirin is one of the world’s most commonly used drugs.2 With antiinflammatory and antiplatelet properties, it was first proposed as a treatment to prevent preeclampsia in 1978.3 Since then, there have been many randomized clinical trials evaluating the effectiveness of aspirin to prevent preeclampsia.4, 5, 6, 7, 8AJOG at a Glance
Aspirin is widely offered to pregnant women to prevent preeclampsia, one of the most severe obstetrical complications. Large studies of nonpregnant populations taking aspirin to prevent cardiovascular events have decisively shown an increased risk of major hemorrhage. However, there have not been large, adequately powered studies to determine whether there is a risk of bleeding in a pregnant population.
In this population-based register cohort study of 313,624 pregnancies, aspirin use was associated with a clear increased risk of bleeding during labor and the postpartum period.
These findings provide clear evidence against more liberal or universal administration of aspirin.
Aspirin is now widely offered to women thought to be at an increased risk of developing preeclampsia, a practice that is recommended by most guidelines.9, 10, 11, 12, 13 These generally recommend that pregnant women at high risk or with more than 1 moderate risk factor for preeclampsia take 75 to 150 mg of aspirin daily, from 12 weeks of gestation until 36 to 37 weeks of gestation,13 or until birth.10,11,14 Sweden has had a conservative approach with regard to aspirin, and only women considered high risk based on medical and obstetrical history have been offered 75 mg of aspirin from 12 to 36 weeks of gestation. The new 2019 Swedish guidelines are very similar to the National Institute for Health and Care Excellence (NICE) guidelines, where 10% of the pregnant population are expected to be classified as high risk and offered aspirin.11
Given the perceived safety of aspirin during pregnancy, there have even been increasing calls to simply administer aspirin universally to all pregnant women.15, 16, 17 A cost-effective analysis published in 2019 theorized that universal administration may prevent 346 cases of preeclampsia and save $8,011,725 compared with the current US Preventative Services Task Force guidelines.18 Notably, this calculation had an underlying assumption that aspirin is safe, where the authors only considered gastrointestinal bleeding and aspirin-exacerbated respiratory disease as possible adverse effects and did not consider the potential for pregnancy-related bleeding complications.18
However, studies of nonpregnant populations have found a consistent association between chronic administration of aspirin and bleeding risk. Recent large randomized trials investigating aspirin for the primary prevention of major cardiovascular events in an older population report an increased risk of bleeding complications.19, 20, 21, 22 A recent meta-analysis of 164,225 participants reported an increased risk for major bleeding complications (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.30–1.56) and intracranial hemorrhage (HR, 1.34; 95% CI, 1.14–1.57) among primary prevention aspirin users,23 which was confirmed in a second meta-analysis.24
To our knowledge, there are no population-based studies addressing whether there is a bleeding risk with aspirin administration during pregnancy (literature search terms presented in Supplemental Table 1). It is a challenging question to examine because aspirin is freely available without a prescription in most countries, but in Sweden, aspirin is a prescribed medication. Sweden also has high-quality national population and quality registers, including the Swedish Pregnancy Register. In the Swedish Pregnancy Register, clinical information is recorded in a uniform manner and medication use is routinely recorded at all trimesters of pregnancy, including aspirin. Therefore, we undertook a population-based register cohort study investigating whether there is an association between aspirin use and bleeding during pregnancy and delivery.