NEW YORK (Reuters Health) – By spotting pregnant women at risk for preeclampsia and starting them on low-dose aspirin before 16 weeks’ gestation, physicians can more than halve the risk of preeclampsia, preterm birth and intrauterine growth retardation (IUGR), a meta-analysis shows.

Thus, “women considered at high-risk to develop preeclampsia, mainly those with prior preeclampsia” should receive low-dose aspirin starting by 16 weeks, Dr. Emmanuel Bujold, from Universite Laval, Quebec, told Reuters Health via email.

Preeclampsia and IUGR are related to defective placentation, Dr. Bujold and colleagues explain in the August issue of Obstetrics & Gynecology. As a result, inadequate perfusion and placental ischemia are believed to evoke endothelial dysfunction, with platelet and clotting system activation. If that’s so, then aspirin should prevent vasoconstriction and pathological blood coagulation in the placenta that causes preeclampsia and IUGR.

The problem is that randomized trials of prenatal aspirin have had contradictory results.

Dr. Bujold’s team theorized that starting aspirin too late in pregnancy and including low-risk women in the trials could account for the negative results.

Through a search of Embase, PubMed and the Cochrane database, they identified 34 randomized controlled trials published between 1985 and 2005. The 11,348 subjects had risk factors for preeclampsia including nulliparity; multiple pregnancy; history of preeclampsia, other hypertensive disorders, IUGR, or stillbirth; or an abnormal Doppler ultrasound of the uterine artery.

Those in the treatment group took aspirin 50-150 mg/day, either alone or with dipyridamole less than 300 mg daily, while those in the control group were allocated to placebo or no treatment. The authors stratified the studies according to gestational age at randomization (at or before 16 weeks, 12 studies; after 16 weeks, 22 studies).

Only in studies where women were started on aspirin before 16 weeks were there significant differences between treatment and control groups in rates of preeclampsia, preterm birth, and IUGR.

In the early treatment group, compared with placebo, aspirin significantly lowered the risk of preeclampsia (relative risk 0.47), IUGR less than the 10th centile, (RR 0.47), and preterm birth (RR 0.22), with numbers needed to treat of 8 or 9.

Furthermore, the authors report, early aspirin treatment resulted in gestational age at delivery that was 1.4 weeks greater than in the placebo group.

“We found no increased risk for antepartum bleeding” or risk of early pregnancy loss, Dr. Bujold noted. “However, it is unclear if we should start the aspirin as soon as the pregnancy test is positive or if we should wait until 8-12 weeks.”

Besides their practical implications, the study findings help confirm the mechanism underlying preeclampsia.

“The ‘implantation of the placenta’ or the ‘invasion of the spiral arteries in the uterus by the trophoblasts’ is usually completed by 16-18 weeks,” Dr. Bujold explained. “We believe that aspirin helps this physiological mechanism that can be deficient in some women. In fact, we showed previously that failure of the physiological transformation of the spiral arteries by the trophoblast cells is a hallmark of preeclampsia.”

He and his associates are now planning a randomized controlled trial using low-dose aspirin in women with abnormal first-trimester biochemical markers used for predicting trisomy 21, such as maternal Papp-A, which are associated with preeclampsia.

“It would be great if we can predict and prevent preeclampsia in women at their first pregnancy,” Dr. Bujold concluded.


Prevention of Preeclampsia and Intrauterine Growth Restriction With Aspirin Started in Early Pregnancy: A Meta-Analysis

Obstet Gynecol 2010;116:402-414.