OBJECTIVE
The association between aspirin use during pregnancy and the risk of postpartum hemorrhage
remains unclear. This study aimed to explore the incidence of postpartum hemorrhage
and the amount of postpartum blood loss among women who used aspirin during pregnancy.
DATA SOURCES
From inception to October 2022, this study searched the following databases: MEDLINE,
Web of Science, Embase, and the Cochrane Central Register of Controlled Trials.
STUDY ELIGIBILITY CRITERIA
Studies comparing pregnancy outcomes that covered the incidence of postpartum hemorrhage
or the amount of postpartum blood loss in pregnancies with aspirin vs placebo (or
no aspirin) were included.
METHODS
Reviewers separately ascertained studies, obtained data, and gauged study quality.
The meta-analysis was conducted using a random effects model owing to the probable
heterogeneity of the included studies. The rates of postpartum hemorrhage or the mean
amounts of postpartum blood loss were compared, and the odds ratios or mean differences
with 95% confidence intervals were estimated. Of note, 2 parts performed both a pooled
analysis of randomized controlled trials and cohort studies and a separate analysis
of randomized controlled trials.
RESULTS
Overall, 21 studies with 373,926 women were included in the postpartum hemorrhage
part, and 7 studies with 10,163 women were included in the postpartum blood loss part.
The results suggested that aspirin (dose 60-150mg a day) use during pregnancy was
associated with an increased incidence of postpartum hemorrhage (odds ratio, 1.20;
95% confidence interval, 1.07–1.34). When only randomized controlled trials were retained,
the results remained significant (odds ratio, 1.12; 95% confidence interval, 1.00–1.25).
In the second part, higher total blood loss after delivery was obtained (mean difference,
12.85 mL; 95% confidence interval, 3.28–22.42), and the result was unaltered when
cohort studies were eliminated (mean difference, 13.72 mL; 95% confidence interval,
4.63–22.81). The conclusions are more likely to be obtained in developed countries.
CONCLUSION
Low-dose aspirin use during pregnancy is a potential risk of postpartum hemorrhage
and does slightly increase the amount of postpartum blood loss. Without denying the
combined value of aspirin, our conclusions raised an alarm for clinicians about postpartum
hemorrhage in women using aspirin during pregnancy.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & Gynecology MFMAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global causes of maternal death: a WHO systematic analysis.Lancet Glob Health. 2014; 2 (e323–33)
- Postpartum hemorrhage.N Engl J Med. 2021; 384: 1635-1645
- Practice Bulletin No. 183: postpartum hemorrhage.Obstet Gynecol. 2017; 130 (e168–86)
- Postpartum hemorrhage: a comprehensive review of guidelines.Obstet Gynecol Surv. 2022; 77: 665-682
- How should we diagnose and assess the severity of PPH in clinical trials?.Best Pract Res Clin Obstet Gynaecol. 2019; 61: 41-54
- Quantitative blood loss in obstetric hemorrhage: ACOG Committee Opinion, Number 794.Obstet Gynecol. 2019; 134: e150-e156
- Prevention and management of postpartum hemorrhage: a comparison of 4 national guidelines.Am J Obstet Gynecol. 2015; 213 (76.e1–10)
- The mechanism of action of aspirin.Thromb Res. 2003; 110: 255-258
- Mechanism of the irreversible inhibition of human cyclooxygenase-1 by aspirin as predicted by QM/MM calculations.J Mol Graph Model. 2013; 40: 99-109
- Aspirin for prevention of preeclampsia.Drugs. 2017; 77: 1819-1831
- Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.Lancet. 2020; 395: 285-293
- The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.Am J Obstet Gynecol. 2017; 216 (110–120.e6)
- Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.N Engl J Med. 2017; 377: 613-622
- Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.N Engl J Med. 1993; 329: 1213-1218
- Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement.JAMA. 2021; 326: 1186-1191
- Aspirin for primary prevention of cardiovascular events.J Am Coll Cardiol. 2019; 73: 2915-2929
- Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial.Gut. 2021; 70: 717-724
- Effect of nabumetone and aspirin on colonic mucosal bleeding time.Aliment Pharmacol Ther. 2001; 15: 539-542
- Ischemic benefit and hemorrhage risk of ticagrelor-aspirin versus aspirin in patients with acute ischemic stroke or transient ischemic attack.Stroke. 2021; 52: 3482-3489
- 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)
- Effects of low-dose aspirin on the prevention of preeclampsia and pregnancy outcomes: a randomized controlled trial from Shanghai, China.Eur J Obstet Gynecol Reprod Biol. 2020; 248: 156-163
- Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis.JAMA. 2019; 321: 277-287
- Meta-analysis on the effect of aspirin use for prevention of preeclampsia on placental abruption and antepartum hemorrhage.Am J Obstet Gynecol. 2018; 218: 483-489
- The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ. 2021; 372: n71
- RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019; 366: l4898
Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2021. Available at: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed November 15, 2020.
- How to perform a meta-analysis with R: a practical tutorial.Evid Based Ment Health. 2019; 22: 153-160
- CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group.Lancet. 1994; 343: 619-629
- ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA (Estudo Colaborativo para Prevencao da Pre-eclampsia com Aspirina) Collaborative Group.Br J Obstet Gynaecol. 1996; 103: 39-47
- A randomized controlled trial of low-dose aspirin in women at risk from pre-eclampsia.Int J Gynaecol Obstet. 1998; 60: 129-135
- Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.N Engl J Med. 1998; 338: 701-705
- A randomised trial of low dose aspirin for primiparae in pregnancy. The Jamaica Low Dose Aspirin Study Group.Br J Obstet Gynaecol. 1998; 105: 293-299
- Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications.Br J Obstet Gynaecol. 1998; 105: 286-292
- Aspirin (100 mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Regional Aspirine Mere-Enfant study (Part 1).BJOG. 2003; 110: 475-484
- Randomized controlled trial using low-dose aspirin in the prevention of pre-eclampsia in women with abnormal uterine artery Doppler at 23 weeks’ gestation.Ultrasound Obstet Gynecol. 2003; 22: 233-239
- Prevention of gravidic endothelial hypertension by aspirin treatment administered from the 8th week of gestation.Hypertens Res. 2011; 34: 1116-1120
- Chronotherapy with low-dose aspirin for prevention of complications in pregnancy.Chronobiol Int. 2013; 30: 260-279
- Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.Ultrasound Obstet Gynecol. 2017; 49: 435-441
- Trial of feasibility and acceptability of routine low-dose aspirin versus Early Screening Test indicated aspirin for pre-eclampsia prevention (TEST study): a multicentre randomised controlled trial.BMJ Open. 2018; 8e022056
- Role of aspirin in high pulsatility index of uterine artery: a consort study.J Obstet Gynaecol India. 2018; 68: 382-388
- Aspirin and pre-eclampsia prevention in women with pre-existing diabetes: a retrospective study.Intern Med J. 2021; 51: 1673-1680
- Low-dose aspirin for primary prevention of adverse pregnancy outcomes in twin pregnancies: an observational cohort study based on propensity score matching.BMC Pregnancy Childbirth. 2021; 21: 786
- Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): a multicentre, randomised, double-blinded, placebo-controlled trial.PLoS Med. 2022; 19e1003892
- A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.Am J Obstet Gynecol. 2022; 226 (251.e1–12)
- Low dose aspirin for preeclampsia prevention and postpartum blood loss.Am J Obstet Gynecol. 2022; (S75–6)
- Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy-induced hypertension. Italian study of aspirin in pregnancy.Lancet. 1993; 341: 396-400
- Low dose aspirin treatment in late pregnancy differentially inhibits cyclo-oxygenase in maternal platelets.Prostaglandins. 1987; 34: 717-722
- The angiotensin sensitivity test and low-dose aspirin are ineffective methods to predict and prevent hypertensive disorders in nulliparous pregnancy.Am J Obstet Gynecol. 1995; 173: 865-872
- Low-dose aspirin therapy and hypertensive pregnancy complications in unselected IVF and ICSI patients: a randomized, placebo-controlled, double-blind study.Hum Reprod. 2010; 25: 2972-2977
- Risk factors for atonic postpartum hemorrhage: a systematic review and meta-analysis.Obstet Gynecol. 2021; 137: 305-323
- Systemic erythematosus lupus and pregnancy outcomes in a Colombian cohort.Lupus. 2021; 30: 2310-2317
- The role of aspirin dose and initiation time in the prevention of preeclampsia and corresponding complications: a meta-analysis of RCTs.Arch Gynecol Obstet. 2022; 305: 1465-1479
- Aspirin use to prevent preeclampsia and related morbidity and mortality: updated evidence report and systematic review for the US Preventive Services Task Force.JAMA. 2021; 326: 1192-1206
- Low-dose aspirin at ≤16 weeks of gestation for preventing preeclampsia and its maternal and neonatal adverse outcomes: a systematic review and meta-analysis.Exp Ther Med. 2018; 15: 4361-4369
- Antiplatelet agents for preventing pre-eclampsia and its complications.Cochrane Database Syst Rev. 2019; 2019CD004659
- Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches.BJOG. 2002; 109: 161-167
- Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14-16 weeks pregnancy: randomized controlled clinical trial.Croat Med J. 2005; 46: 826-831
- Neonatal intracranial hemorrhage and maternal use of aspirin.Obstet Gynecol. 1981; 58: 52S-56S
- The risks and benefits of taking aspirin during pregnancy.Epidemiol Rev. 1990; 12: 108-148
- Impact of low-dose aspirin on adverse perinatal outcome: meta-analysis and meta-regression.Ultrasound Obstet Gynecol. 2020; 55: 157-169
Article info
Publication history
Published online: January 24, 2023
Accepted:
January 18,
2023
Received in revised form:
January 14,
2023
Received:
January 10,
2023
Footnotes
The authors report no conflict of interest.
This work was supported by the National Key Research and Development Program of China (grant number 2021YFC2701502).
This study was registered with the International Prospective Register of Systematic Reviews (registration number CRD42022373254).
This paper has not been presented at any meetings.
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
