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Low-dose aspirin to prevent preeclampsia

Serena Williams

Recently in the media, Beyoncé (singer) and Serena Williams (professional tennis player) opened up about their experience with a potentially fatal pregnancy complication – preeclamsia.

So, what do these women have in common apart from being famous? They are both African American, both recently have given birth, and both had to deliver earlier then their due date via emergency C-section since their health, and their babies’ was in danger. They experienced difficult pregnancies, long recoveries, as well as the extra monitoring and care required for their babies post-delivery.

What is preeclampsia (PE)?

PE, also known as toxaemia in the US, is a disorder characterised by the onset of hypertension/high blood pressure (?140/90mmHg) after 20 weeks of pregnancy, and in some cases can persist up to 6 weeks after birth.

To be classified as PE, hypertension must be associated with either proteinuria (protein excreted by kidneys), and/ accompanied by an evidence of damage to other organs such as kidney, liver, brain and eyes. 

How common is PE and what are its complications?

PE is one of the top causes of maternal death (end organ damage, blood clot formation, stroke) and fetal complications (preterm delivery, placenta detachment from the uterine wall, fetal growth restriction) and occurs in around 10% of pregnancies. 

Symptoms and signs of PE

Some women may not have any symptoms, whilst others may experience some of the following with varying severity:

  • epigastric pain
  • headache
  • seizures
  • blurry vision
  • oedema in the legs, face and hands
  • cough, shortness of breath

Some of the signs that your obstetrician may discover during routine tests are:

  • Hemolysis – Red blood cell destruction
  • Elevated liver enzymes
  • Low platelets
  • Protein in the urine
  • Low urine production

Who is more likely to have PE?

Certain women are at higher risk then others to develop PE. Your obstetrician will assess your family history and clinical markers to determine your individual risk.

Some of the factors that are considered are:

  • First pregnancy
  • Multiple pregnancy
  • Race: African
  • Mothers > 35 years
  • Family history of PE
  • Hypertension
  • Diabetes
  • Obesity (BMI >30)

Why do these complications occur?

No one knows for sure why PE occurs in some women. But the key feature that has been identified in affected women is the development of the abnormal placenta.

Normally during pregnancy, the arteries to the placenta are well formed and significantly dilated, to ensure plentiful blood supply to the growing fetus. In PE these placental arteries become fibrous, narrow, and limit blood flow.  The outcome is poorly perfused placenta, which is associated with fetal intrauterine growth restriction (IUGR) and in severe cases fetal death.

Furthermore, this under-perfused placenta starts releasing pro-inflammatory proteins called antiangiogenic factors. These proteins then get into the mother’s circulation and alter the endothelial cells function that line her blood vessels.

This means that the woman’s vascular function is less able to adapt to the required physiological pregnancy changes leading to: narrowing of the blood vessels and reduced blood supply to vital organs. Endothelial cell damage also causes increased blood clotting around the sites of injury, oedema, and leads kidney to retain more salt. All these factors combined contribute to hypertension that is observed in PE and its complications.

PE prevention – low-dose aspirin (LDA)

Once PE develops, apart from managing hypertension in pregnancy and close monitoring, the only other treatment is delivery of the fetus and placenta. One of the preventative measures for PE that has been studied in depth is LDA prophylaxis in at risk women.

There are no definite screening tests that predict the development of PE, but women with moderate to high risk of PE may be identified. Taking preventative LDA in the early of the second trimester, may reduce incidence of PE in this subgroup of women.

It is thought that aspirin assists in prevention of PE by reduced clotting action of platelets, dilating blood vessels and decreasing inflammation. 

Aspirin’s evidence in reducing PE frequency and its complications

Evidence shows:

  • LDA is best to be started early, ? 16 week of pregnancy.
  • Optimum aspirin dose range: 100-150mg daily.
  • Continue daily until 36 weeks of gestation.
  • Best benefit in moderate-high risk women and PE incidence reduced by 10-20%.
  • Fetal complications are also reduced (preterm birth, IUGR)
  • If PE develops LDA will no longer be useful and best to be stopped.
  • Universal LDA is not recommended to all pregnant women due to small risk of bleeding.

Conclusion

There are no screening tests for pregnant women that can definitely predict the development of PE, but moderate to high risk women can be identified. Preventative measures for PE are a continuously researched and guidelines are updated. LDA has the strongest evidence to date for prevention of PE. Your obstetrician is in the best position to assess your individual risk criteria for PE and make suitable recommendations. 

References:

  1. Rolnik DL et al. (2017) Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. New England Journal of Medicine. 377 (7): 613.
  2. Roberge S et al. (2017) The role of aspirin dose on the prevention of preeclamsia and fetal growth restriction; systematic review and meta-analysis. American Journal of Obstetrics and Gynaecology. 216 (2): 110.
  3. Roberge S et al. (2018) Aspirin for the prevention of preterm and term preeclamsia: systematic review and meta-analysis. American Journal of Obstetrics and Gynaecology. 218 (3): 287.
  4. Meta-analysis. (1993) Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy induced hypertension. Italian study of aspirin in pregnancy. Lancet. 342 (8842): 396
  5. Caritis S et al. (1998) Low-dose aspirin to prevent preeclamsia in women at high risk. New England Journal of Medicine. 338 (11): 701.
  6. Collaborative group. (1994) CLASP: a randomized trial of low-dose aspirin for the prevention and treatment of pre-eclampsia amount 9364 pregnant women. Lancet. 343 (8898): 619.
  7. Henderson JT et al. (2014) Low-dose aspirin for prevention of morbidity and mortality from preeclamsia: a systematic evidence review for the US Preventive Services Task Force. Annals of Internal Medicine. 160 (10): 695.
  8. Brown MA et al. (2018) The hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Pregnancy Hypertension. 13: 291.
  9. Lowe SA et al. (2014) Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) regarding the Management of Hypertensive Disorders of Pregnancy. Available from: https://www.somanz.org/documents/HTPregnancyGuidelineJuly2014.pdf Accessed: 28 September 2018.
  10. Mone F et al. (2017) Should we recommend universal aspirin for all pregnant women? American Journal of Obstetrics & Gynecology. 216 (2): 141.