Preeclampsia Prevention

Pathophysiology

Preeclampsia is primarily caused by poor placentation, characterized by inadequate trophoblastic invasion of the myometrium, poor remodeling of spiral arteries, and reduced uteroplacental perfusion, leading to restricted blood flow to the placenta 1
Two waves of trophoblastic invasion occur: decidual invasion at 8-10 weeks and myometrial invasion at 16-18 weeks, which is crucial for proper placentation 1
Aspirin prevents preeclampsia through its anti-inflammatory, antiangiogenesis, and antiplatelet properties that counteract the pathophysiological processes of endothelial dysfunction and imbalance between thromboxane A2 and prostacyclin 2

Aspirin reduces systemic inflammation associated with preeclampsia and enhances vasodilation, improving endothelial function 2
Aspirin may modulate inflammatory factors that affect the endometrium and uterine/ovarian vasculature prior to pregnancy, potentially improving implantation rates 1

Aspirin is most effective when started before 16 weeks of gestation, ideally between 12-16 weeks, with higher doses (≥100 mg) appearing more effective in reducing preeclampsia 1
Most guidelines recommend a daily dose of 81 mg (US) or 75-162 mg (Canadian/ISSHP) 3
Preconception initiation of 75-100 mg aspirin is safe in pregnancy and may be beneficial for conception benefits 1

Obesity and chronic hypertension may limit aspirin effectiveness due to altered pharmacokinetics, limited absorption, and preexisting vascular damage 1
Low-dose aspirin may be most beneficial for women with previous pregnancy losses, women with infertility undergoing IVF, women with conditions affecting placentation, and women with risk factors for preeclampsia who are trying to conceive 1, 2, 4
Aspirin should be used with caution in the last trimester due to potential bleeding risks 3
A systematic review showed a significant decrease in preterm birth <37 weeks (5.3% vs. 10%, RR 0.52, CI: 0.27-0.97, p=0.04) with low-dose aspirin initiated prior to conception or before 11 weeks in women with infertility or recurrent pregnancy loss 1
Low-dose aspirin increases blood flow velocity in uterine and ovarian arteries, which can enhance the implantation environment, and is associated with improved implantation rates in women undergoing in vitro fertilization 1
The American College of Obstetricians and Gynecologists recommends low-dose aspirin for women with risk factors for preeclampsia or those with infertility/recurrent pregnancy loss 2