Am J Perinatol 2023; 40(13): 1390-1397
DOI: 10.1055/a-2096-5199
SMFM Fellowship Series Article

Low-Dose Aspirin during Pregnancy and Postpartum Bleeding

Kelsey J. White
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
,
Moeun Son
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
,
Lisbet S. Lundsberg
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
,
Jennifer F. Culhane
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
,
Caitlin Partridge
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
,
Uma M. Reddy
2   Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York
,
Audrey A. Merriam
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
› Author Affiliations
Funding None.

Abstract

Objective This study aimed to investigate whether aspirin 81 mg daily for preeclampsia prevention is associated with increased risk of postpartum blood loss at the time of delivery.

Study Design This is a retrospective cohort study performed at a tertiary hospital from January 2018 to April 2021. Data were extracted from the electronic medical record. Patients prescribed low-dose aspirin (LDA) were compared with patients who were not. The primary outcome was a composite of postpartum blood loss, defined as: estimated blood loss (EBL) >1,000 mL, documentation of International Classification of Diseases-9/-10 codes for postpartum hemorrhage (PPH), or red blood cell (RBC) transfusion. Bivariate analysis, and unadjusted and adjusted logistic regression modeling were performed.

Results Among 16,980 deliveries, 1,922 (11.3%) were prescribed LDA. Patients prescribed LDA were more likely to be >35 years old, nulliparous, obese, taking other anticoagulants, or have diagnoses of diabetes, systemic lupus erythematosus, fibroids, or hypertensive disease of pregnancy. After adjusting for potential confounders, the significant association between LDA use and the composite did not persist (adjusted odds ratio [aOR]: 1.1, 95% confidence interval [CI]: 1.0–1.3) nor did the association between EBL > 1,000 mL (aOR: 1.0, 95% CI: 0.9–1.3) and RBC transfusion (aOR: 1.3, 95% CI: 0.9–1.7). The association between LDA and PPH remained significant (aOR: 1.3, 95% CI: 1.1–1.6). Patients who discontinued LDA <7 days prior to delivery had an increased risk of the postpartum blood loss composite compared discontinuation ≥7 days (15.0 vs. 9.3%; p = 0.03).

Conclusion There may be an association between LDA use and increased risk of postpartum bleeding. This suggests that use of LDA outside the recommended guidelines should be cautioned and further investigation is needed to determine its ideal dosing and timing of discontinuation.

Key Points

  • There may be an association with LDA and an increased risk of postpartum bleeding.

  • Patients who discontinued LDA less than 7 days prior to delivery had an increased rate of postpartum bleeding.

  • Additional research is need to determine optimal LDA dose and timing of discontinuation.

Presentation

Oral presentation (Abstract no.: 93) at the 42nd Annual Pregnancy Meeting, Society of Maternal Fetal Medicine, held virtually, January 31–February 5, 2022.


Supplementary Material



Publication History

Received: 27 October 2022

Accepted: 19 May 2023

Accepted Manuscript online:
21 May 2023

Article published online:
19 June 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Kuklina EV, Ayala C, Callaghan WM. Hypertensive disorders and severe obstetric morbidity in the United States. Obstet Gynecol 2009; 113 (06) 1299-1306
  • 2 Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2019; 124 (07) 1094-1112
  • 3 ACOG Committee Opinion No. ACOG Committee Opinion No. 743: low-dose aspirin use during pregnancy. Obstet Gynecol 2018; 132 (01) e44-e52
  • 4 Combs CA, Montgomery DM. SMFM Patient Safety and Quality Committee. Electronic address: smfm@smfm.org. Society for Maternal-Fetal Medicine Special Statement: checklists for preeclampsia risk-factor screening to guide recommendations for prophylactic low-dose aspirin. Am J Obstet Gynecol 2020; 223 (03) B7-B11
  • 5 Davidson KW, Barry MJ, Mangione CM. et al; US Preventive Services Task Force. Aspirin use to prevent preeclampsia and related morbidity and mortality: US preventive services task force recommendation statement. JAMA 2021; 326 (12) 1186-1191
  • 6 Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V. Aspirin for prevention of preeclampsia. Drugs 2017; 77 (17) 1819-1831
  • 7 Rolnik DL, Wright D, Poon LC. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017; 377 (07) 613-622
  • 8 Hastie R, Tong S, Wikström AK, Sandström A, Hesselman S, Bergman L. Aspirin use during pregnancy and the risk of bleeding complications: a Swedish population-based cohort study. Am J Obstet Gynecol 2021; 224 (01) 95.e1-95.e12
  • 9 Caritis S, Sibai B, Hauth J. et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Low-dose aspirin to prevent preeclampsia in women at high risk. N Engl J Med 1998; 338 (11) 701-705
  • 10 CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet 1994; 343 (8898): 619-629
  • 11 Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007; 369 (9575): 1791-1798
  • 12 Henderson JT, O'Connor E, Whitlock EP. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia. Ann Intern Med 2014; 161 (08) 613-614
  • 13 Henderson JT, Vesco KK, Senger CA, Thomas RG, Redmond N. 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 (12) 1192-1206
  • 14 Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2019; 2019 (10) CD004659
  • 15 Mone F, Mulcahy C, McParland P. et al. 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; 8 (07) e022056
  • 16 US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA 2022;327(16):15777#x2013;1584
  • 17 Guirguis-Blake J, Evans C, Perdue L, Bean S, Senger CUS. Preventive Services Task Force evidence syntheses, formerly systematic evidence reviews. In: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: An Evidence Update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality (US); 2021
  • 18 Dehmer S, O'Keefe L, Grossman E, Maciosek M. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: An Updated Decision Analysis for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality (US); 2021
  • 19 Ikeda Y, Shimada K, Teramoto T. et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA 2014; 312 (23) 2510-2520
  • 20 Bowman L, Mafham M, Wallendszus K. et al; ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018; 379 (16) 1529-1539
  • 21 McNeil JJ, Wolfe R, Woods RL. et al; ASPREE Investigator Group. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018; 379 (16) 1509-1518
  • 22 Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA 2019; 321 (03) 277-287
  • 23 Mahmoud AN, Gad MM, Elgendy AY, Elgendy IY, Bavry AA. Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J 2019; 40 (07) 607-617
  • 24 De Berardis G, Lucisano G, D'Ettorre A. et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA 2012; 307 (21) 2286-2294
  • 25 de Groot NL, Hagenaars MP, Smeets HM, Steyerberg EW, Siersema PD, van Oijen MG. Primary non-variceal upper gastrointestinal bleeding in NSAID and low-dose aspirin users: development and validation of risk scores for either medication in two large Dutch cohorts. J Gastroenterol 2014; 49 (02) 245-253
  • 26 Gaziano JM, Brotons C, Coppolecchia R. et al; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018; 392 (10152): 1036-1046
  • 27 Devereaux PJ, Mrkobrada M, Sessler DI. et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370 (16) 1494-1503
  • 28 Gerstein NS, Carey MC, Cigarroa JE, Schulman PM. Perioperative aspirin management after POISE-2: some answers, but questions remain. Anesth Analg 2015; 120 (03) 570-575
  • 29 Koenig-Oberhuber V, Filipovic M. New antiplatelet drugs and new oral anticoagulants. Br J Anaesth 2016; 117 (Suppl. 02) ii74-ii84
  • 30 Wolff G, Navarese EP, Brockmeyer M. et al. Perioperative aspirin therapy in non-cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Int J Cardiol 2018; 258: 59-67
  • 31 Werner EF, Hauspurg AK, Rouse DJ. A cost-benefit analysis of low-dose aspirin prophylaxis for the prevention of preeclampsia in the United States. Obstet Gynecol 2015; 126 (06) 1242-1250
  • 32 Mallampati D, Grobman W, Rouse DJ, Werner EF. Strategies for prescribing aspirin to prevent preeclampsia: a cost-effectiveness analysis. Obstet Gynecol 2019; 134 (03) 537-544