Thirteen trials (13,324 women: 6,694 in the treatment groups and 6,540 in the control groups) were included.
Only 2 studies reported a significant reduction in the odds of intra-uterine growth reduction with aspirin treatment. All other studies showed non significant results. The combined OR was 0.82 (95% CI: 0.72, 0.93, p=0.003), representing a significant risk reduction of 18% with aspirin therapy.
None of the studies showed a significant protective effect of aspirin therapy on perinatal mortality. The combined OR was 0.84 (95% CI: 0.66, 1.08, p=0.18).
Subgroup analysis suggests that aspirin was more effective at higher doses (100 to 150 mg/day) than lower doses (50 to 80 mg/day): ORs for intra-uterine growth reduction were 0.36 (95% CI: 0.22, 0.59) and 0.87 (95% CI: 0.76, 0.99), respectively. In addition, treatment started before 17 weeks' gestation was more effective than that started after: ORs for intra-uterine growth reduction were 0.35 (95% CI: 0.21, 0.58) and 0.87 (95% CI: 0.76, 0.99), respectively.
A sensitivity analysis excluding trials of lower methodological quality did not substantially alter the results.
Funnel plots show that the possibilty of publication bias cannot be dismissed. The tests for heterogeneity for both outcomes yielded non significant results, but given the low power of the test, heterogeneity in the complete set of trials cannot be dismissed.