Thirty-eight RCTs (n=30,349) were included in the review.
Prematurity.
When the results of all 22 studies were pooled, women taking aspirin had a lower risk of pre-term delivery than women receiving a placebo (RR 0.92, 95% CI: 0.86, 0.98). A subgroup analysis of 14 studies evaluating the risk of pre-term delivery in women exposed to aspirin before 24 weeks' gestation was less conclusive. Two studies reported a significantly lower risk of pre-term delivery in women taking aspirin compared with placebo, but when all 14 studies were pooled the RR was 0.92 (95% CI: 0.84, 1.00).
A subgroup analysis of 6 studies evaluating the risk of pre-term delivery in women exposed to aspirin after 24 weeks' gestation showed no significant reduction in pre-term delivery in women taking aspirin compared with placebo (RR 0.66, 95% CI: 0.41, 1.04).
Birth weight.
When the results of all 29 studies were pooled, women who took aspirin gave birth to heavier babies than women who took a placebo (WMD 43 g, 95% CI: 18, 67).
A subgroup analysis in women exposed to 75 mg/day aspirin also showed a significantly higher birth weight for babies born of women taking aspirin compared with offspring of women taking a placebo (WMD 43 g 95% CI: 15, 71). However, unlike the other analyses undertaken, the studies in this analysis were statistically heterogeneous (chi-squared P=0.021).
A subgroup analysis in women exposed to more than 75 mg/day aspirin showed no significant difference in birth weight between babies born of women taking aspirin and those of women taking a placebo.
Twelve studies reported on the incidence of small for gestational age. There was no statistically significant difference between babies born of women taking aspirin and those of women taking a placebo. A subgroup analysis of 6 studies where women started taking aspirin before 24 weeks' gestation showed similar results (i.e. no significant difference) in the incidence of small for gestational age.
Miscarriage.
Seven RCTs reported no difference in the risk of miscarriage between women taking aspirin in their first or second trimester, compared with women taking a placebo.
Still birth or perinatal death.
One of the 20 studies reported a statistically significant reduction in risk of perinatal mortality in women taking aspirin compared with placebo. When the results of the 20 studies were pooled, there was no significant effect of aspirin exposure on perinatal mortality.
No statistically significant effect of aspirin exposure on perinatal mortality was found in the subgroup analysis of women taking aspirin before 24 weeks' gestation, women taking up to 75 mg/day of aspirin compared with placebo, higher doses of aspirin compared with placebo, or when still birth and perinatal death were analysed separately.
Apgar score.
There was no statistically significant difference in the risk of an Apgar score lower than 7, five minutes after delivery, in babies born of women taking aspirin compared with those of women taking a placebo (7 RCTs).
Neonatal asphyxia.
There was no significant difference in neonatal asphyxia in babies born of women taking aspirin compared with those of women taking a placebo (3 RCTs).
Bleeding in the neonate.
There was no significant difference in neonatal bleeding between women taking aspirin and women taking a placebo (12 RCTs).