Low-dose aspirin use in the first trimester of pregnancy and odds of congenital anomalies: A meta-analysis of randomized controlled trials

Background Daily low-dose aspirin (LDA) is recommended in high-risk pregnancies. However, its safety profile in the first trimester has not been well documented. Objectives To determine if LDA exposure during the first trimester of pregnancy is associated with higher odds of congenital structural anomalies. Search Strategy PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and were systematically searched. Selection Criteria Randomized controlled trials (RCTs) that assigned participants to LDA (<= 150 mg) or placebo/no intervention at less than 14 weeks of pregnancy were eligible. Data Collection and Analysis Random-effects models were performed using the inverse-variance method to calculate pooled effect sizes. Quality of evidence was appraised according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Main Results Eight RCTs that included 7564 participants assigned to receive daily LDA and 7670 participants that served as controls were analyzed. Low-certainty evidence showed no significant difference in the odds of congenital anomalies (odds ratio 0.87, 95% confidence interval 0.62-1.23, I-2 = 0%). Conclusions In this meta-analysis, there is no evidence to suggest safety concerns regarding LDA teratogenicity. However, given the overall low quality of evidence, further research (e.g. individual participant data meta-analysis) is needed to confirm LDA safety profile.