Background: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. Antiplatelet agents might prevent the development of pre-eclampsia. Objectives: to assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia. Subgroup analyses by maternal risk, gestation at entry (<20>weeks), use of placebo and dose of aspirin (<75mg>) were pre-specified.
Methods: of the Cochrane Collaboration and its Pregnancy and Childbirth Group were used. All randomised trials comparing antiplatelet agents (predominantly aspirin) with either placebo or no antiplatelet agent in pregnant women considered to be at risk of developing pre-eclampsia were eligible. Results are expressed as relative risk (RR) and number needed to treat (NNT) with 95% confidence intervals.
Results: The use of antiplatelet agents is associated with; 1) a 15% reduction in the risk of pre-eclampsia (32 trials with 29,331 women; RR 0.85, 0.78-0.92; NNT 89, 59 - 167). This reduction is regardless of risk status at trial entry but appears to be greater when a placebo is not used, when the dose of aspirin is greater or gestation at randomisation earlier. 2) A 7% reduction in the risk of delivery before 37 completed weeks (23 trials with 28,268 women, RR 0.92, 0.88-0.97, NNT 72, 44 - 200); 3) a 14% reduction in fetal or neonatal deaths (30 trials with 30,093 women, RR 0.86, 0.75- 0.99). This reduction in death seemed greatest amongst high risk women (4134 women; RR 0.73, 0.56-0.96). There are no significant differences between treatment and control groups in the incidence of small for gestational age babies (25 trials 20,235 women, RR 0.91, 0.83-1.00), placental abruption, induction of labour or caesarean section. Funnel plots indicate a marked skew towards small positive trials, which might be due to publication bias or a different effect in women at higher baseline risk.
Conclusions: Despite the potential benefits overall, it is not possible to make clear recommendations for clinical practice from this review. Safety has only been documented for low dose aspirin. Many of these unresolved questions about baseline risk and timing of treatment could be most efficiently answered by a review pooling the individual patient data. Interested collaborators are invited to contact either Lelia Duley (email@example.com) or David Henderson-Smart (firstname.lastname@example.org)