Volume 51, Issue 10, October 2022

Indications for commencing aspirin for the prevention of pregnancy-induced hypertension and pre-eclampsia spectrum disorders

PDM Pathiraja    Nada Abu Alrub    Gargeswari Sunanda   
doi: 10.31128/AJGP-01-22-6289   |    Download article
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Hypertensive disorders of pregnancy are a leading cause of maternal, fetal and neonatal morbidity.1 Furthermore, they are a leading cause of maternal mortality in countries with developing economies. Evidence suggests there is a reduction in the risk of pre-eclampsia toxaemia when low-dose aspirin (LDA) therapy is initiated in early pregnancy.2 For women diagnosed with pregnancy-induced hypertension, the risk of recurrence is 20% in subsequent pregnancies. Additionally, this risk increases significantly for women diagnosed with pre-eclampsia requiring delivery before 37 weeks’ gestation.1 The indications for starting LDA for prevention of pre-eclampsia are based on the presence of at least one high-risk factor, or two or more moderate-risk factors (Table 1).

Table 1. Clinical risk assessment for pre-eclampsia
High risk factors* Moderate risk factors*
Previous pregnancy complicated with hypertension, pre-eclampsia spectrum disorders or HELLP syndrome1,3,9 Primigravida1,9
Multifetal gestation9 Age ≥40 years1
Age ≥35 years9
Chronic hypertension1,3,9 More than 10-year pregnancy interval1,9
Type 1 or 2 diabetes mellitus1,3,9 BMI >30 kg/m2 at first visit9
BMI >35 kg/m2 at first visit1
Chronic kidney disease1,3,9 Family history of PET (mother or sister)1,9
Autoimmune disease (eg systemic lupus erythematosus, antiphospholipid syndrome, scleroderma)1,3,9 Low socioeconomic status
Personal history of low birth weight
Previous adverse pregnancy outcomes9
Assisted conception with oocyte donation3 Multifetal gestation1
*Recommend low-dose aspirin if the patient has at least one of the high-risk factors or two or more moderate-risk factors
BMI, body mass index; HELLP, haemolysis, elevated liver enzymes and low platelets

The pathophysiology of pre-eclampsia is not fully understood; however, it may be attributed to suboptimal trophoblast invasion during placental formation, which leads to an imbalance of angiogenic and antiangiogenic factors causing endothelial damage and widespread inflammation. Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and primarily acts by inhibiting cyclooxygenase isoenzymes (COX-1 and COX-2) at different dosages. At lower dosages it irreversibly inhibits COX-1, decreasing the platelet synthesis of a vasoconstrictive product of thromboxane A2 without affecting the vascular wall production of vasodilatory substance of prostacyclin.

According to the current best evidence, aspirin 100–150 mg daily is recommended for high-risk groups, ideally before 16 weeks’ gestation and as early as 12 weeks’ gestation,1,3–5 and number needed to treat is approximately 42–70, relative risk: 0.76 (95% confidence interval: 0.62, 0.95).6,7 The 2014 Society of Obstetric Medicine of Australia and New Zealand guideline for the management of hypertensive disorders of pregnancy, endorsed by Australasian Diabetes in Pregnancy Society, recommends LDA for women with moderate to high risk of pre-eclampsia spectrum disorders.8

Moreover, the American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal and Fetal Medicine states that there is still some benefit if aspirin is commenced prior to 28 weeks’ gestation.9 The National Institute for Health and Care Excellence and ACOG recommend prescribing LDA from 12 weeks’ gestation until birth,1 which supersedes their previous statement of continuing until 36 weeks’ gestation, on the basis of new evidence.9,10 Continuation of LDA until birth has not been associated with an increase in haemorrhagic complications6 such as placental abruption or postpartum haemorrhage, nor is it a contraindication for regional anaesthesia.11 Moreover, systematic reviews have not shown an increase in congenital anomalies, neonatal haemorrhage or premature ductal closure associated with LDA.6 Aspirin should be avoided for patients with a history of aspirin-exacerbated respiratory disease (‘Samter’s triad’), gastrointestinal bleeding, genitourinary bleeding, active peptic ulcer disease and/or hepatic dysfunction.12

Prophylactic LDA is not indicated for prevention of unexplained stillbirths or fetal growth restriction alone without other risk factors for pre-eclampsia.6,13 Cochrane and systematic reviews report that a low dose of daily calcium (500 mg) started in early pregnancy may reduce the risk of pre-eclampsia, especially for women at high risk and women with low dietary calcium intake.14 Supplements such as magnesium, vitamin C and vitamin E do not help prevent hypertensive disorders in pregnancy.1,3,9

It has been observed in clinical practice that aspirin is often not commenced until later in pregnancy in Australia; that is, until the second or early third trimester when the patient is seen in secondary care by an obstetric specialist. This is contrary to evidence-based best practice. Further, we do understand if the general practitioners (GPs) experience some barriers to early commencement of medicine for various reasons until the patient is seen by an obstetric specialist. However, we emphasise that GPs in Australia should consider and screen all pregnant women for risk factors of pre-eclampsia at early antenatal visits and commence aspirin early to achieve optimum results in preventing pre-eclampsia.

Competing interests: None.
Provenance and peer review: Not commissioned, externally peer reviewed.
Funding: None.
Correspondence to:
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  1. National Institute for Health and Care Excellence. Hypertension in pregnancy: Quality standard. Manchester, UK: NICE, 2019. Available at [Accessed 15 August 2022]. Search PubMed
  2. Rolnik DL, Wright D, Poon LC, et al. Aspirin vs placebo in pregnancies with high risk for preterm pre-eclampsia. N Engl J Med 2017;377(7):613–22. doi: 10.1056/NEJMoa1704559. Search PubMed
  3. New Zealand College of Midwives. Guidance regarding the use of low dose aspirin in the prevention of pre-eclampsia in high-risk women. Christchurch, NZ: NZCOM, 2018. Search PubMed
  4. Rolnik DL, Wright D, Poon LC, et al. ASPRE trial: Performance of screening for preterm pre-eclampsia. Ultrasound Obstet Gynecol 2017;50(4):492–95. doi: 10.1002/uog.18816. Search PubMed
  5. Sentilhes L, Azria E, Schmitz T. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017;377(24):2399–400. doi: 10.1056/NEJMc1713798. Search PubMed
  6. Henderson JT, Whitlock EP, O’Connor E, Senger CA, Thompson JH, Rowland MG. 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):695–70. doi: 10.7326/M13-2844. Search PubMed
  7. Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens 2014;4(2):97–104. doi: 10.1016/j.preghy.2014.02.001. Search PubMed
  8. Lowe SA, Bowyer L, Lust K, et al. SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust N Z J Obstet Gynaecol 2015;55(5):e1–e29. doi: 10.1111/ajo.12399. Search PubMed
  9. ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstet Gynecol 2018;132(1):e44–e52. doi: 10.1097/AOG.0000000000002708. Search PubMed
  10. Schisterman EF, Silver RM, Lesher LL, et al. preconception low dose aspirin and pregnancy outcomes results from the EAGeR randomised trial. Lancet 2014;384(9937):29–36. doi: 10.1016/S0140-6736(14)60157-4. Search PubMed
  11. Narouze S, Benzon HT, Provenzano DA, et al. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: Guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Reg Anesth Pain Med 2015;40(3):182–212. doi: 10.1097/AAP.0000000000000223. Search PubMed
  12. The Australian Medicines Handbook. Australian Medicines Handbook online 2022 [online]. Adelaide, SA: Australian Medicines Handbook, 2022. Search PubMed
  13. Askie LM, Duley L Henderson-Smart DJ, Stewert LA, PARIS Collaborative Group. Antiplatelets agents for prevention of preeclampsia: A metanalysis of individual patient data. Lancet 2007;369(9575):1971–98. doi: 10.1016/S0140-6736(07)60712-0. Search PubMed
  14. Hofmeyr GJ, Betrán AP, Singata-Madliki M, et al. Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2019;393(10169),330–39. doi: 10.1016/S0140-6736(18)31818-X. Search PubMed

AspirinPre-eclampsiaPregnancyPregnancy-induced hypertension

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