Modern aspects of the use of acetylsalicylic acid in pregnant women


DOI: https://dx.doi.org/10.18565/therapy.2023.8.57-64

Chulkov V.S., Nikolenko E.S., Chulkov Vl.S., Okonenko T.I., Zhmaylova S.V.

1) Institute of Medical Education of Yaroslav the Wise Novgorod State University, Veliky Novgorod; 2) South Ural State Medical University of the Ministry of Healthcare of Russia, Chelyabinsk
Abstract. Low doses of acetylsalicylic acid (ASA) are widely used to prevent preeclampsia and associated pregnancy complications. A common mechanism underlying these pregnancy complications is uteroplacental insufficiency. Since preeclampsia increases both morbidity and mortality, primary prevention is the main goal of optimizing both short-term and long-term health of mother and child. Secondary prevention in women with previous hypertensive disorders during pregnancy is also justified due to the increased risk of relapse during the next pregnancy. Despite the fact that the mechanism of influence of ASA is not definitively known, it is believed that it improves placentation due to its antithrombotic and vasodilating action, as well as restoring the imbalance of thromboxane and prostacyclin in endothelial cells. This review systematizes modern studies devoted to the study of the effect of ASA on the prevention of pregnancy complications from the standpoint of evidence-based medicine.
Keywords: antiphospholipid syndrome, preeclampsia, acetylsalicylic acid, pregnancy, prevention
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Literature

1. Schiff E., Peleg E., Goldenberg M. et al. The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. N Engl J Med. 1989; 321(6): 351–56. https://dx.doi.org/10.1056/NEJM198908103210603.


2. Wallenburg H.C., Dekker G.A., Makovitz J.W. et al. Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae. Lancet. 1986; 1(8471): 1–3. https://dx.doi.org/10.1016/s0140-6736(86)91891-x.


3. Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994; 330(18): 1287–94. https://dx.doi.org/10.1056/NEJM199405053301808.


4. Cadavid A.P. Aspirin: The mechanism of action revisited in the context of pregnancy complications. Front Immunol. 2017; 8: 261. https://dx.doi.org/10.3389/fimmu.2017.00261.


5. Roberts J.M., King T.L., Barton J.R. et al. Care plan for individuals at risk for preeclampsia: shared approach to education, strategies for prevention, surveillance, and follow-up. Am J Obstet Gynecol. 2023; 229(3): 193–213. https://dx.doi.org/10.1016/j.ajog.2023.04.023.


6. Duley L., Meher S., Hunter K.E. et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2019; 2019(10): CD004659. https://dx.doi.org/10.1002/14651858.CD004659.pub3.


7. Henderson J.T., Vesco K.K., Senger C.A. et al. 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): 1192–206. https://dx.doi.org/10.1001/jama.2021.8551.


8. Wright D., Rolnik D.L., Syngelaki A., et al. Aspirin for evidence-based preeclampsia prevention trial: Effect of aspirin on length of stay in the neonatal intensive care unit. Am J Obstet Gynecol. 2018; 218(6): 612.e1–612 e6. https://dx.doi.org/10.1016/j.ajog.2018.02.014.


9. Roberge S., Nicolaides K.H., Demers S. et al. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: A meta-analysis. Ultrasound Obstet Gynecol. 2013; 41(5): 491–99. https://dx.doi.org/10.1002/uog.12421.


10. Coomarasamy A., Honest H., Papaioannou S. et al. Aspirin for prevention of preeclampsia in women with historical risk factors: A systematic review. Obstet Gynecol. 2003; 101(6): 1319–32. https://dx.doi.org/10.1016/s0029-7844(03)00169-8.


11. Стрюк Р.И., Бунин Ю.А., Гурьева В.М. с соавт. Диагностика и лечение сердечно-сосудистых заболеваний при беременности 2018. Национальные рекомендации. Российский кардиологический журнал. 2018; 23(7): 156–200. [Stryuk R.I., Bunin Yu.A., Guryeva V.M. et al. Diagnosis and treatment of cardiovascular diseases during pregnancy 2018. National guidelines. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2018; 23(7): 156–200 (In Russ.)]. https://dx.doi.org/10.15829/1560-4071-2018-7-156-200. EDN: XUZQTZ.


12. Meher S., Duley L., Hunter K. et al. Antiplatelet therapy before or after 16 weeks’ gestation for preventing preeclampsia: An individual participant data meta-analysis. Am J Obstet Gynecol. 2017; 216(2): 121–28.e2. https://dx.doi.org/10.1016/j.ajog.2016.10.016.


13. Henderson J.T., Whitlock E.P., O’Connor E. et al. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: A systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2014; 160(10): 695–703. https://dx.doi.org/10.7326/M13-2844.


14. Ходжаева З.С., Холин А.М., Чулков В.С., Муминова К.Т. Ацетилсалициловая кислота в профилактике преэклампсии и ассоциированных акушерских и перинатальных осложнений. Акушерство и гинекология. 2018; (8): 12–19. [Khodzhaeva Z.S., Kholin A.M., Chulkov V.S., Muminova K.T. Acetylsalicylic acid in the prevention of preeclampsia and associated obstetric and perinatal complications. Akusherstvo i ginekologiya = Obstetrics and Gynecology. 2018; (8): 12–19 (In Russ.)]. https://dx.doi.org/10.18565/aig.2018.8.12-18. EDN: SAFJOD.


15. Rolnik D.L., Wright D., Poon L.C. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017; 377(7): 613–22. https://dx.doi.org/10.1056/NEJMoa1704559.


16. US Preventive Services Task Force, Davidson K.W., Barry M.J., Mangione C.M. et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021; 326(12): 1186–91. https://dx.doi.org/10.1001/jama.2021.14781.


17. American College of Obstetricians and Gynecologists’ Practice Advisory: Low-dose aspirin use for the prevention of preeclampsia and related morbidity and mortality. September 2023. URL: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/09/low-dose-aspirin-use-for-the-prevention-of-preeclampsia-and-related-morbidity-and-mortality (date of access – 01.10.2023).


18. Hauspurg A., Sutton E.F., Catov J.M. et al. Aspirin effect on adverse pregnancy outcomes associated with stage 1 hypertension in a high-risk cohort. Hypertension. 2018; 72(1): 202–7. https://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11196.


19. Chaemsaithong P., Cuenca-Gomez D., Plana M.N. et al. Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia? Am J Obstet Gynecol. 2020; 222(5): 437–50. https://dx.doi.org/10.1016/j.ajog.2019.08.047.


20. Tong S., Mol B.W., Walker S.P. Preventing preeclampsia with aspirin: does dose or timing matter? Am J Obstet Gynecol. 2017; 216(2): 95–97. https://dx.doi.org/10.1016/j.ajog.2016.12.003.


21. Roberge S., Nicolaides K., Demers S. et al. 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(2): 110–20.e6. https://dx.doi.org/10.1016/j.ajog.2016.09.076.


22. Roberge S., Bujold E., Nicolaides K.H. Aspirin for the prevention of preterm and term preeclampsia: Systematic review and metaanalysis. Am J Obstet Gynecol. 2018; 218(3): 287–93.e1. https://dx.doi.org/10.1016/j.ajog.2017.11.561.


23. Ayala D.E., Ucieda R., Hermida R.C. Chronotherapy with low-dose aspirin for prevention of complications in pregnancy. Chronobiol Int. 2013; 30(1–2): 260–79. https://dx.doi.org/10.3109/07420528.2012.717455.


24. Hermida R.C., Ayala D.E., Calvo C., et al. Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients. J Am Coll Cardiol. 2005; 46(6): 975–83. https://dx.doi.org/10.1016/j.jacc.2004.08.071.


25. Rolnik D.L., Nicolaides K.H., Poon L.C. Prevention of preeclampsia with aspirin. Am J Obstet Gynecol. 2022; 226(2S): S1108–19. https://dx.doi.org/10.1016/j.ajog.2020.08.045.


26. Navaratnam K., Alfirevic A., Jorgensen A., Alfirevic Z. Aspirin non-responsiveness in pregnant women at high-risk of pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2018; 221: 144–50. https://dx.doi.org/10.1016/j.ejogrb.2017.12.052.


27. Kini V., Ho P.M. Interventions to improve medication adherence: A review. JAMA. 2018; 320(23): 2461–73. https://dx.doi.org/10.1016/j.ejogrb.2017.12.052.


28. Hirsh J., Guyatt G., Albers G.W. et al. Executive summary: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008; 133(6 Suppl): 71S–109S. https://dx.doi.org/10.1378/chest.08-0693.


29. Mendoza M., Bonacina E., Garcia-Manau P. et al. Aspirin discontinuation at 24 to 28 weeks’ gestation in pregnancies at high risk of preterm preeclampsia: A randomized clinical trial. JAMA. 2023; 329(7): 542–50. https://dx.doi.org/10.1001/jama.2023.0691.


30. Roberge S., Bujold E., Nicolaides K.H. Meta-analysis on the effect of aspirin use for prevention of preeclampsia on placental abruption and antepartum hemorrhage. Am J Obstet Gynecol. 2018; 218(5): 483–89. https://dx.doi.org/10.1016/j.ajog.2017.12.238.


31. Kozer E., Nikfar S., Costei A. et al. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: A meta-analysis. Am J Obstet Gynecol. 2002; 187(6): 1623–30. https://dx.doi.org/10.1067/mob.2002.127376.


32. Naimi A.I., Perkins N.J., Sjaarda L.A. et al. The effect of preconception-initiated low-dose aspirin on human chorionic gonadotropin-detected pregnancy, pregnancy loss, and live birth: Per protocol analysis of a randomized trial. Ann Intern Med. 2021; 174(5): 595–601. https://dx.doi.org/10.7326/M20-0469.


33. 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(8898): 619–29.


34. Landman A.J.E.M.C, van Limburg Stirum E.V.J., de Boer M.A. et al. Long-term health and neurodevelopment in children after antenatal exposure to low-dose aspirin for the prevention of preeclampsia and fetal growth restriction: A systematic review of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol. 2021; 267: 213–20. https://dx.doi.org/10.1016/j.ejogrb.2021.11.010.


35. Navaratnam K., Alfirevic A., Alfirevic Z. Low dose aspirin and pregnancy: how important is aspirin resistance? BJOG. 2016; 123(9): 1481–87. https://dx.doi.org/10.1111/1471-0528.13914.


36. Empson M., Lassere M., Craig J.C., Scott J.R. Recurrent pregnancy loss with antiphospholipid antibody: A systematic review of therapeutic trials. Obstet Gynecol. 2002; 99(1): 135–44. https://dx.doi.org/10.1016/s0029-7844(01)01646-5.


37. Mak A., Cheung M.W., Cheak A.A., Ho R.C. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford) 2010; 49(2): 281–88. https://dx.doi.org/10.1093/rheumatology/kep373.


38. Hamulyak E.N., Scheres L.J.J., Goddijn M., Middeldorp S. Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome – What is the evidence? J Thromb Haemost. 2021; 19(5): 1174–85. https://dx.doi.org/10.1111/jth.15290.


39. Yang Z., Shen X., Zhou C. et al. Prevention of recurrent miscarriage in women with antiphospholipid syndrome: A systematic review and network meta-analysis. Lupus. 2021; 30(1): 70–79. https://dx.doi.org/10.1177/0961203320967097.


40. Erkan D. The relation between antiphospholipid syndrome-related pregnancy morbidity and non-gravid vascular thrombosis: a review of the literature and management strategies. Curr Rheumatol Rep. 2002; 4(5): 379–86. https://dx.doi.org/10.1007/s11926-002-0081-2.


41. Infante-Rivard C., David M., Gauthier R. et al. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss. A case-control study. N Engl J Med. 1991; 325(15): 1063–66. https://dx.doi.org/10.1056/NEJM199110103251503.


42. Soh M.C., Pasupathy D., Gray G. et al. Persistent antiphospholipid antibodies do not contribute to adverse pregnancy outcomes. Rheumatology (Oxford). 2013; 52(9): 1642–47. https://dx.doi.org/10.1093/rheumatology/ket173.


43. Chighizola C.B., de Jesus G.R. Antiphospholipid antibodies and infertility. Lupus. 2014; 23(12): 1232–38. https://dx.doi.org/10.1177/0961203314529171.


44. Levine A.B., Lockshin M.D. Assisted reproductive technology in SLE and APS. Lupus. 2014; 23(12): 1239–41. https://dx.doi.org/10.1177/0961203314527370.


45. Del Ross T., Ruffatti A., Visentin M.S. et al. Treatment of 139 pregnancies in antiphospholipid-positive women not fulfilling criteria for antiphospholipid syndrome: a retrospective study. J Rheumatol. 2013; 40(4): 425–29. https://dx.doi.org/10.3899/jrheum.120576.


46. Вереина Н.К., Чулков В.С., Чулков Вл.С., Мовчан Т.В. Взаимосвязь длительной персистенции антифосфолипидных антител с клиническим и лабораторным профилем риска у женщин. Терапия. 2020; 6(1): 52–58. [Vereina N.K., Chulkov V.S., Chulkov Vl.S., Movchan T.V. Relationship of long-term persistence of antiphospholipid antibodies with clinical and laboratory risk profile in women. Terapiya = Therapy. 2020; 6(1): 52–58 (In Russ.)]. https://dx.doi.org/10.18565/therapy.2020.1.52-58. EDN: FXXFFI.


47. Tincani A., Branch W., Levy R.A. et al. Treatment of pregnant patients with antiphospholipid syndrome. Lupus. 2003; 12(7): 524–29. https://dx.doi.org/10.1191/0961203303lu393oa.


48. Fishman P., Falach-Vaknin E., Sredni B. et al. Aspirin modulates interleukin-3 production: additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome. J Rheumatol. 1995; 22(6): 1086–90.


49. Вереина Н.К., Чулков В.С. Ацетилсалициловая кислота – «палитра возможностей» в профилактике и лечении сердечно-сосудистых заболеваний. РМЖ. 2015; 23(5): 288–292. [Vereina N.K., Chulkov V.S. Acetylsalicylic acid – «palette of possibilities» in the prevention and treatment of cardiovascular diseases. Rossiyskiy meditsinskiy zhurnal = Russian Medical Journal. 2015; 23(5): 288–292 (In Russ.)]. EDN: UBGVLP.


50. Amengual O., Fujita D., Ota E. et al. Primary prophylaxis to prevent obstetric complications in asymptomatic women with antiphospholipid antibodies: A systematic review. Lupus. 2015; 24(11): 1135–42. https://dx.doi.org/10.1177/0961203315578765.


About the Autors

Vasily S. Chulkov, MD, professor of the Department of internal diseases of the Institute of Medical Education, Yaroslav the Wise Novgorod State University. Address: 173003, Veliky Novgorod, 41 Bol`shaya Sankt-Peterburgskaya St.
E-mail: vschulkov@rambler.ru
ORCID: https://orcid.org/0000-0002-0952-6856
Ekaterina S. Nikolenko, senior laboratory assistant at the Department of faculty therapy, South Ural State Medical University of the Ministry of Healthcare of Russia. Address: 454092, Chelyabinsk, 64 Vorovskogo St.
E-mail: nikolenkokate@yandex.ru
ORCID: https://orcid.org/0000-0003-4958-4695
Vladislav S. Chulkov, PhD in Medical Sciences, associate professor of the Department of faculty therapy, South Ural State Medical University of the Ministry of Healthcare of Russia. Address: 454092, Chelyabinsk, 64 Vorovskogo St.
E-mail: vlad.chulkov.1989@mail.ru
ORCID: https://orcid.org/0000-0002-1948-8523
Tatyana I. Okonenko, MD, head of the Department of general pathology of the Institute of Medical Education, Yaroslav the Wise Novgorod State University. Address: 173003, Veliky Novgorod, 41 Bol`shaya Sankt-Peterburgskaya St.
E-mail: Tatiana.okonenko@novsu.ru
ORCID: https://orcid.org/0000-0002-7431-3777
Svetlana V. Zhmaylova, MD, head of the Department of additional professional education and polyclinic therapy of the Institute of Medical Education, Yaroslav the Wise Novgorod State University. Address: 173003, Veliky Novgorod, 41 Bol`shaya Sankt-Peterburgskaya St.
E-mail: svetlana.zhmaylova@novsu.ru
ORCID: https://orcid.org/0000-0002-7754-5338


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