Aspirin During Pregnancy Reduces Pre-Eclampsia Risks

CAMPERDOWN, Australia, May 17 – Aspirin therapy during pregnancy may modestly reduce pre-eclampsia risk, but unknown long-term effects require weighing the decision with each patient, researchers said.

A meta-analysis of patient-level data found that antiplatelet agents were associated with a 10% reduction in relative risk of pre-eclampsia (P=0.004) and preterm birth (P=0.011), said Lisa Askie, Ph.D., M.P.H., of the University of Sydney here, and colleagues.

But even the extensive subgroup and sensitivity analyses yielded no group of women who would clearly benefit more or less than the overall group, they reported online in The Lancet.

"Deciding on the benefit-to-risk ratio is difficult," according to an accompanying editorial by James M. Roberts, M.D., and Janet M. Catov, Ph.D., both of the University of Pittsburgh.

"The decision is one that is probably best made individually in consultation with an informed mother," the editorialists added.

Because part of the damage associated with pre-eclampsia is thought to occur through activation of platelets and the clotting system, antiplatelet agents have been widely tested for primary prevention in randomized trials, the researchers wrote.

Their research, the PARIS (Perinatal Antiplatelet Review of International Studies) Collaboration, consisted of a systematic review and meta-analysis on individual patient data from 32,217 women and their 32,819 babies randomized in 31 trials.

The studies looked at primary prevention using low-dose aspirin (50 to 150 mg per day) or dipyridamole (Persantine) versus a placebo or no antiplatelet agent.

The women were deemed to be at risk of pre-eclampsia, gestational hypertension, or intra-uterine growth restriction based on previous pregnancy history, a pre-existing medical condition, or obstetric risk factors early in the current pregnancy, such as first pregnancy or twins.

Three trials randomized women to a combination of aspirin and dipyridamole and another three, smaller trials randomized women to other antiplatelet agents only, such as dipyridamole, heparin, or ozagrel.

Overall, 8% of the participating women developed pre-eclampsia, similar to the commonly recognized 2% to 8% rate.

The researchers found that 51 women would need to be treated with antiplatelet agents to prevent one serious adverse outcome, defined as maternal death, pre-eclampsia, preterm or small-for-gestational-age birth, or fetal or infant death before discharge from the hospital.

The number needed to treat to prevent one case of pre-eclampsia was 114.

Compared with control subjects, the other results for women who took antiplatelet agents were:

•Significantly lower relative risk of developing pre-eclampsia (RR 0.90, 95% confidence interval 0.84 to 0.97).

•Significantly reduced risk of delivering before 34 weeks (RR 0.90, 95% CI 0.83 to 0.98).

•Significantly lower likelihood of a pregnancy with a serious adverse outcome (RR 0.90, 95% CI 0.85 to 0.96).

•No difference in risk of fetal or infant death before discharge alone (RR 0.91, 95% CI 0.81 to 1.03).

•No difference in risk of an infant being born small for its gestational age (RR 0.90, 95% CI 0.81 to 1.02).

•No difference in bleeding events for either women (antepartum RR 1.02, 95% 0.90 to 1.15, or postpartum RR 1.06, 95% CI 1.00 to 1.13) or their babies (RR 0.93, 95% CI 0.80 to 1.09).

No subgroup was substantially more or less likely to benefit from antiplatelet agents, the researchers reported.

This included the groups traditionally considered to be at high risk, such as women with pre-eclampsia in more than one pregnancy (P=0.56) and women with chronic hypertension and pre-eclampsia in a previous pregnancy (P=0.25).

Dr. Askie and colleagues cautioned, though, that these analyses were based on small numbers of women, because most women in the trials were at low to moderate risk of pre-eclampsia.

"Thus, despite having gathered an extremely large dataset," they wrote, "the evidence base for particular groups of high-risk women remains limited and the most appropriate estimate of relative risk reduction remains the overall estimate of 10%."

They noted, though, that they found no groups for whom withholding antiplatelet therapy would be justified.

From a public-health perspective, they wrote, the moderate benefits they found may argue for more widespread use of antiplatelet agents.

Editorialists Drs. Roberts and Catov added that aspirin is justified as primary prevention for women with pre-eclampsia in more than one pregnancy or women with chronic hypertension and pre-eclampsia in a previous pregnancy.

Despite safety in terms of acute outcomes as seen in the PARIS data, the editorialists cautioned, "as with all therapy in pregnancy, long-range implications (unknown) must be thought about."

Both the researchers and the editorialists suggested using the information to counsel individual women considering aspirin for primary prevention of pre-eclampsia.

"This information should be discussed with women at risk of pre-eclampsia to help them make informed choices about their antenatal care," the investigators concluded. "Whether individual women will choose to take antiplatelet agents might depend on an assessment of their absolute risk."