Low-dose aspirin treatment in pregnancy

July 30, 2010 — Low-dose aspirin treatment of pregnant women at risk for preeclampsia can more than halve the risk of preeclampsia, preterm birth and intrauterine growth retardation (IUGR), a meta-analysis shows.

"Women considered at high-risk to develop preeclampsia, mainly those with prior preeclampsia" should take low-dose aspirin every day, starting by 16 weeks, lead author Dr. Emmanuel Bujold, from Universite Laval, Quebec, told Reuters Health via email.

"However," he added, "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."

Preeclampsia and IUGR are related to defective placentation, he and his colleagues explain in the August issue of Obstetrics & Gynecology. It's believed that as a result, inadequate perfusion and placental ischemia lead to 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. The research 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 trials included 11,348 women with risk factors for preeclampsia, e.g., nulliparity, multiple pregnancy, abnormal Doppler ultrasound of the uterine artery, or a history of preeclampsia, other hypertensive disorders, IUGR, or stillbirth.

Treatment groups received aspirin 50-150 mg/day, either alone or with dipyridamole less than 300 mg daily; control groups received placebo or no treatment. The authors stratified the studies according to gestational age at randomization (through 16 weeks, 12 studies; after 16 weeks, 22 studies).

Only when treatment started before 16 weeks did the researchers see significant differences 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, gestational age was 1.4 weeks greater with aspirin treatment than with placebo, the authors report.

"We found no increased risk for antepartum bleeding" or risk of early pregnancy loss, Dr. Bujold noted.

Besides their practical implications, the findings help confirm the mechanism of 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."

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

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.

Obstet Gynecol. 2010;116:402-414.

Reuters Health Information 2010. © 2010 Reuters Ltd.