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

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 http://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.

Prediction and prevention of preeclampsia in women with preexisting diabetes: the role of home blood pressure, physical activity, and aspirin

“…Although prophylactic aspirin in low doses is considered safe for use in pregnancy, its use might increase the risk of bleeding, e.g., epistaxis, small skin bleedings, gastrointestinal discomfort, or postpartum hemorrhage ( 6 , 98 , 106 , 107 ). A few older studies have raised concern for congenital anomalies including gastroschisis and cryptorchidism after fetal exposure to aspirin in analgetic doses in early pregnancy ( 108 – 110 ), but this has not been found in a recent meta-analysis ( 111 ). Prophylactic low-dose aspirin is mainly initiated after the organogenesis and is discontinued around 36–37 gestational weeks, i.e., well before labor normally starts.…”

Low-Dose Aspirin after ASPRE—More Questions Than Answers? Current International Approach after PE Screening in the First Trimester

“…Therefore, it should be explained in detail to every patient why higher doses must be used in her treatment whenever that is necessary. To date, no association of LDA with the development of birth defects, malformations, miscarriages, and premature closure of the ductus arteriosus has been detected [ 58 , 59 , 60 , 61 ]. One study evaluating the use of paracetamol, ibuprofen, and aspirin on 185,617 pregnant patients showed the possibility of increased risk of cerebral palsy in women exposed to aspirin during pregnancy.…”

Effect of low dose aspirin application during pregnancy on fetal congenital anomalies

“…One RCT study enrolling 1,288 women, among whom 615 started using LDA before pregnancy and kept taking the medication throughout the whole pregnancy, suggested that exposure to LDA during pregnancy did not increase the risk of congenital malformations [12]. A recent meta-analysis included 8 RCTs (7564 participants assigned to LDA less than 14 weeks of gestation and 7670 serving as controls) and the results suggested no evidence of safety concerns regarding LDA teratogenicity [13]. However, LDA exposure of less than 14 weeks was selected as the criterion to delineate the first trimester rather than the embryonic period which demonstrates the critical window of teratogenicity.…”