Thirty-four RCTs were included in the review. Sample sizes ranged from 33 to 6,275 women. Data were reported on women enrolled prior to 16 weeks gestation in 12 trials. Twenty-two trials reported data collected from women who were enrolled after 16 weeks completed gestation. Twenty-three trials adequately reported randomisation methods. Intention-to-treat analyses were used in 14 trials. Double-blinding was reported in 16 trials and single blinding in two trials. There was no blinding in five trials and blinding was not reported in six trials.
Twenty-seven RCTs (n=11,348) assessed the incidence of pre-eclampsia. There were statistically significant decreases in incidence across trials that included women who commenced treatment with low-dose aspirin both before and after 16 completed weeks gestation (RR 0.68, 95% CI 0.54 to 0.86, I2=52%). There was a slightly statistically significant reduction in IUGR across 24 trials (n=8,733) that examined this outcome (RR 0.85, 95% CI 0.72 to 1.00, I2=28%).
Statistically significant benefits were observed for women who commenced treatment with low-dose aspirin prior to 16 weeks gestation. There was less risk of pre-eclampsia (RR 0.47, 95% CI 0.34 to 0.65; nine trials, n=764), severe pre-eclampsia (RR 0.09, 95% CI 0.02 to 0.37; three trials, n=278), IUGR (RR 0.44, 95% CI 0.30 to 0.65; nine trials, n=853), IUGR less than the 10th centile (RR 0.47, 95% CI 0.30 to 0.74; five trials n=414), gestational hypertension (RR 0.62 95% CI 0.45 to 0.84; seven trials, n=548) and preterm birth (RR 0.22, 95% CI 0.10 to 0.49; four trials, n=387). There were no differences between the low-dose aspirin and control groups in the risk of placental abruption. No statistical heterogeneity was reported for risks of pre-eclampsia and IUGR, but I2 values were not reported for the other outcomes.
For the women who started treatment with low-dose aspirin after 16 weeks completed gestation, there were significant reductions in risk of gestational hypertension (RR 0.63, 95% CI 0.47 to 0.85; 14 trials, n=4,303) and preterm birth (RR 0.90, 95% CI 0.83 to 0.97; 16 trials, n=10,398). There were no statistically significant differences in risks of pre-eclampsia, IUGR and placental abruption.
Visual appraisal of the funnel plot suggested a possibility of publication bias with an absence of small studies that showed no benefits in groups of women enrolled prior to 16 weeks completed gestation; the result of the Egger's test confirmed this (p=0.03) for this group of women.