A brief overview and latest evidence of the application of Aspirin in pregnancy-related complications

1. Low-Dose Aspirin Use During Pregnancy
The application of Aspirin in pregnancy‐related complications
Presenter: Clerk 楊 憶
Supervisor: VS 王彥筑 醫師

2. Indications for LDA during pregnancy ?
Current Guidelines
• ACOG 2018
...Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be
initiated between 12–28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery...
• NICE 2019
...Advise pregnant women at high risk of pre-eclampsia to take 75–150 mg of aspirin daily from 12 weeks until the
birth of the baby...
• ACC/AHA 2020
...Low-dose aspirin, in addition to anticoagulation, may be used to prevent thrombosis in pregnant patients with a
mechanical heart valve...
• AHA/ASA 2014
...Low-dose aspirin may also be used after the first trimester in patients with low-risk conditions requiring
antiplatelet therapy...
• ACOG 2012
...In women with APS and a history of stillbirth or recurrent fetal loss but no prior thrombotic history, prophylactic
doses of heparin and low-dose aspirin during pregnancy and 6 weeks of postpartum should be considered...
• KDIGO 2012
...Systemic lupus and pregnancy...We suggest administration of low-dose aspirin during pregnancy to decrease the
risk of fetal loss... (2C)

3. • ACOG 2018: Preeclampsia : 1 high risk factor, >1 moderate risk factors
* Not recommended in:
Prior unexplained stillbirth
FGR
Spontaneous preterm birth
Early pregnancy loss
• NICE 2019: 1 high risk factor, >1 moderate risk factors

4. Indications for LDA during pregnancy ?
Current Guidelines
• ACOG 2018
...Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be
initiated between 12–28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery...
• NICE 2019
...Advise pregnant women at high risk of pre-eclampsia to take 75–150 mg of aspirin daily from 12 weeks until the
birth of the baby...
• ACC/AHA 2020
...Low-dose aspirin, in addition to anticoagulation, may be used to prevent thrombosis in pregnant patients with a
mechanical heart valve...
• AHA/ASA 2014
...Low-dose aspirin may also be used after the first trimester in patients with low-risk conditions requiring
antiplatelet therapy...
• ACOG 2012
...In women with APS and a history of stillbirth or recurrent fetal loss but no prior thrombotic history, prophylactic
doses of heparin and low-dose aspirin during pregnancy and 6 weeks of postpartum should be considered...
• KDIGO 2012
...Systemic lupus and pregnancy...We suggest administration of low-dose aspirin during pregnancy to decrease the
risk of fetal loss... (2C)
1. Preeclampsia prophylaxis (patients at high risk)
2. Mechanical heart valve thrombosis prevention
3. Stroke or TIA prevention
4. APS
5. SLE

5. Proposed pathogenesis of preeclampsia

6. Aspirin mechanisms of action in preventing preeclampsia
Loussert, Lola, et al. “Aspirin for Prevention of Preeclampsia and Fetal Growth Restriction.” Prenatal Diagnosis, vol. 40, no. 5, Wiley, Feb. 2020, pp. 519–527.

7. Aspirin mechanisms of action in preventing preeclampsia
Loussert, Lola, et al. “Aspirin for Prevention of Preeclampsia and Fetal Growth Restriction.” Prenatal Diagnosis, vol. 40, no. 5, Wiley, Feb. 2020, pp. 519–527.
Improve disordered placentation →
FGR
Preterm birth
PPROM
Spontaneous abortion
...
May benefit ?

8. Aspirin for the prevention of FGR ?
• In a meta-analysis of 45 RCTs of LDA for prevention of preeclampsia and FGR in
women at high risk, aspirin prophylaxis before 16 weeks of gestation markedly reduced
the incidence of FGR (relative risk [RR] 0.56, 95% CI 0.44-0.70) compared with
placebo/no treatment.
• The reduction was dose dependent
- 75 mg aspirin: RR 0.48, 95% CI: 0,32–0.72
- 150 mg aspirin: RR 0.29, 95% CI: 0.10–0.82
• Low-dose aspirin may be effective when FGR is secondary to preeclampsia since
aspirin appears to reduce the risk of developing preeclampsia in women at moderate to
high risk of developing the disorder.
Am J Obstet Gynecol. 2017 Feb; 216(2):110-120.e6.

9. Aspirin for the prevention of sPTB ?
Berger, Richard et al. “Spontaneous Preterm Birth: Is Prevention with Aspirin Possible?.” Geburtshilfe und Frauenheilkunde vol. 81,3 (2021): 304-310.

10. Aspirin for the prevention of sPTB ?
• The APRIL study (registered in 2017)
• Investigate the impact of 80 mg aspirin on the spontaneous preterm birth rate of women
with a prior history of sPTB
• Primary outcome: Reduction in recurrent preterm birth
Secondary outcome: Poor neonatal outcome

11. Aspirin to reduce risk of pregnancy loss ?
• ...no difference in live births when 1,078 women with one or two prior pregnancy losses
were given low-dose aspirin or placebo before pregnancy (58% versus 53%, P=0.0984).
Lancet. 2014 Jul;384(9937):29-36
• ↑ the trial was subject to nonadherence → per protocol analysis
• ...adhering to LDA for 5 of 7 days per week led to 8 more hCG-detected pregnancies
(95% CI, 4.64 to 10.96 pregnancies), 15 more live births (CI, 7.65 to 21.15 births), and
6 fewer pregnancy losses (CI, -12.00 to -0.20 losses) for every 100 women in the trial.
• Results suggest that preconception use of LDA at least 4 days per week may improve
reproductive outcomes for women who have had 1 or 2 pregnancy losses.
Ann Intern Med. 2021 Jan 26.
doi: 10.7326/M20-0469. Online ahead of print.

12. Aspirin for prevention of stillbirth ?
• When LDA was commenced≤ 16 weeks' gestation, it was associated with a significant
reduction in the risk of perinatal death (RR, 0.47; 95% CI, 0.25-0.88; P = 0.02; number
needed to treat, 92)
• …this risk reduction was only seen when a daily dose of ≥ 100 mg was administered.
• Meta-regression confirmed that the effect of LDA on perinatal death was independent
of any reduction in the rate of PE and preterm birth.
• Limitation: none of the trials were designed to evaluate the impact of aspirin on
perinatal outcome
Ultrasound Obstet Gynecol. 2020;55(2):157.

13. Thank you