Original Research
Obstetrics
Aspirin use during pregnancy and the risk of bleeding complications: a Swedish population-based cohort study

https://doi.org/10.1016/j.ajog.2020.07.023Get rights and content

Background

Aspirin is offered to pregnant women to prevent preeclampsia, a severe obstetrical complication. Large studies of nonpregnant populations have consistently shown that aspirin prophylaxis increases the risk of hemorrhagic complications. However, there have not been any population-based studies investigating this in a pregnant population.

Objective

This study aimed to investigate whether aspirin use during pregnancy is associated with an increased risk of bleeding complications.

Study Design

We performed a register-based cohort study using the Swedish Pregnancy Register wherein we examined 313,624 women giving birth between January 2013 and July 2017. Logistic regression was used to assess the risk of antepartum, intrapartum, and postpartum hemorrhage. A propensity score and inverse probability treatment weighting was used to generate an odds ratio that corrects for differences in baseline characteristics.

Results

Aspirin use was registered in 4088 (1.3%) women during pregnancy. Compared with women who did not take aspirin, aspirin use was not associated with bleeding complications during the antepartum period (adjusted odds ratio, 1.22; 95% confidence interval, 0.97–1.54). However, aspirin users had a higher incidence of intrapartum bleeding (2.9% aspirin users vs 1.5% nonusers; adjusted odds ratio, 1.63; 95% confidence interval, 1.30–2.05), postpartum hemorrhage (10.2% vs 7.8%; adjusted odds ratio, 1.23; 95% confidence interval, 1.08–1.39), and postpartum hematoma (0.4% vs 0.1%; adjusted odds ratio, 2.21; 95% confidence interval, 1.13–4.34). The risk of a neonatal intracranial hemorrhage was also increased (0.07% vs 0.01%; adjusted odds ratio, 9.66; 95% confidence interval, 1.88–49.48). After stratifying by mode of birth, a higher incidence of bleeding among aspirin users was present for those who had a vaginal birth but not those who had a cesarean delivery.

Conclusion

Using aspirin during pregnancy is associated with increased postpartum bleeding and postpartum hematoma. It may also be associated with neonatal intracranial hemorrhage. When offering aspirin during pregnancy, these risks need to be weighed against the potential benefits.

Introduction

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, 8

AJOG 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.

Section snippets

Design and setting

We performed a register-based cohort study using data obtained from the Swedish Pregnancy Register. During 2013, only Stockholm and Gotland regions were included in the register, representing less than one-third of deliveries. However, since 2014, the Swedish Pregnancy Register covers 16 of 20 regions in Sweden (covering 90% of all deliveries) and 98% of all deliveries within the 16 participating regions. The Swedish Pregnancy Register combines prospectively collected data from the Swedish

Results

Of the 313,624 women included in our study, 4088 (1.3%) reported aspirin use during pregnancy. Women using aspirin were older, more obese, and more frequently parous than women who did not take aspirin. In addition, aspirin users were more likely to have a multiple pregnancy, to have conceived through IVF, and to have had a previous cesarean delivery (Table 1). Aspirin users had a higher rate of preexisting medical conditions (including hypertension and diabetes) and pregnancy complications,

Principal findings

In this population-based register study, the use of aspirin during pregnancy was associated with increased bleeding complications in the postpartum period among women giving birth vaginally. Of possible concern, there may also be an increased risk of neonatal intracranial hemorrhage and maternal postpartum hematoma, although numbers were low.

Results

To our knowledge, this is the first population-based register cohort study investigating aspirin use during pregnancy and bleeding complications. Our

Acknowledgments

The authors thank Jonas Söderling and the Swedish Pregnancy Register for data management.

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  • Cited by (0)

    Drs Hastie and Tong contributed equally to this work and are considered co-first authors.

    Drs Hesselman and Bergman contributed equally to this work and are considered co-senior authors.

    The authors report no conflict of interest.

    This study was approved by the Uppsala Ethics Board on August 15, 2018 (approval number: 2018/287).

    The National Health and Medical Research Council of Australia provided salary support to R.H. (#1176922) and S.T. (#1136418). The Center for Clinical Research provided salary support to S.H. (#CKFUU744551) and L.B. (#CKFUU740361).

    Cite this article as: Hastie R, Tong S, Wikström AK, et al. Aspirin use during pregnancy and the risk of bleeding complications: a Swedish population-based cohort study. Am J Obstet Gynecol 2021;224:95.e1-12.

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