Metaanalyses of randomized controlled trials have reported contradictory results about the effect of aspirin in the prevention of preeclampsia, both in terms of the gestational age at the onset of treatment and the dose of the drug. The controversy may be resolved by a metaanalysis that includes several recently published trials and particularly the large Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention trial and by examination of whether there is a difference of the effect of aspirin on preterm vs term preeclampsia.

We performed a systematic review and metaanalysis that evaluated the prophylactic effect of aspirin during pregnancy.

We completed a literature search through PubMed, Cinhal, Embase, Web of Science, and Cochrane library from 1985 to June 2017. Relative risks with random effect were calculated with their 95% confidence intervals.

Sixteen trials that included 18,907 participants provided data for preterm and term preeclampsia. Eight of the included studies were evaluated as being of good quality, and the other 8 studies were deemed to be of poor or uncertain quality. There was high heterogeneity within studies (I² >50%) for preterm and term preeclampsia, but no heterogeneity was found in the subgroup of preterm preeclampsia when the onset of treatment was ≤16 weeks of gestation and the daily dose of aspirin was ≥100 mg (I²=0%). Administration of aspirin was associated with reduction in the risk of preterm preeclampsia (relative risk, 0.62; 95% confidence interval, 0.45–0.87), but there was no significant effect on term preeclampsia (relative risk, 0.92; 95% confidence interval, 0.70–1.21). The reduction in preterm preeclampsia was confined to the subgroup in which aspirin was initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg (relative risk, 0.33; 95% confidence interval, 0.19–0.57). This effect was also observed in the high-quality studies. The reduction in preterm preeclampsia that was observed in the largest trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention; n=1620; relative risk, 0.38; 95% confidence interval, 0.20–0.72) was similar to that in the 5 smaller trials in which aspirin was initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg (n=639; relative risk, 0.22; 95% confidence interval, 0.07–0.66).

Aspirin reduces the risk of preterm preeclampsia, but not term preeclampsia, and only when it is initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg.