ABSTRACT
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 ClinicalTrials.gov 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, I2 = 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.