Twenty-two studies were included: 1 RCT, 6 cohort studies and 15 case-control studies (the number of participants was not reported for all studies).
Overall rates of malformation (1 RCT, 5 cohort and 2 case-control studies; 16,138 exposed participants and 49,890 control participants).
The overall risk of congenital malformation was not statistically significantly higher in the offspring of women exposed to aspirin in the first trimester of pregnancy compared with control participants (OR 1.33, 95% CI: 0.94, 1.89). There was statistically significant heterogeneity (P=0.016); the authors reported separate analyses of the case-control studies alone and the cohort studies together with the RCT.
CNS defects (3 case-control and 1 cohort study).
The risk of congenital CNS defects was not statistically significantly higher in the offspring of women exposed to aspirin compared with control participants (OR 1.39, 95% CI: 0.89, 2.16). There was statistically significant heterogeneity P=0.054); the authors reported a separate analysis of the case-control studies only.
Neural tube defects (3 case-control studies).
The risk of neural tube defects was not statistically significantly higher in the offspring of women exposed to aspirin compared with control participants (OR 2.2, 95% CI: 0.93, 5.17). There was statistically significant heterogeneity (P=0.002). The analysis was repeated after excluding one atypical study.
Congenital heart defects (4 case-control and 2 cohort studies). The risk of congenital heart defects was not statistically significantly higher in the offspring of women exposed to aspirin compared with control participants (OR 1.01, 95% CI: 0.91, 1.12).
Gastroschisis (5 case-control studies).
The risk of gastroschisis was significantly increased in the offspring of women exposed to aspirin compared with control participants (OR 2.37, 95% CI: 1.44, 3.88).
The authors reported further data on congenital anomalies that were reported in only single studies or in only two studies.