1. Low-dose aspirin is not significantly associated with congenital anomalies even when started in the first trimester.
2. Other factors found to be associated with congenital anomalies include history of previous fetal abnormalities and history of previous spontaneous abortions
Evidence Rating Level: 2 (Good)
Low-dose aspirin (LDA) has been used effectively in the treatment of pre-eclampsia, as well as in patients undergoing recurrent pregnancy loss due to thrombophilia. Previous animal studies have found that high-dose aspirin in the first and second trimester was associated with a variety of congenital anomalies. Human studies have also found a possible association between aspirin and fetal gastroschisis and cryptorchidism, as well as concerns regarding premature closure of ductus arteriosus. This retrospective cohort study sought to further expand upon this literature with collected data from 2736 patients and 2856 fetuses, of which 1684 of these patients took LDA, with an average daily dose of 67.6mg. The patients in the LDA group were older, with a higher primipara rate and more previous spontaneous abortions, as well as were more likely to have chronic hypertension and rheumatic disease. Starting at the 12th week of gestation congenital anomalies were screened for every 4 weeks using ultrasound or MRI, karyotype analysis and postpartum examinations. Neonatal examinations were also conducted at birth. The rate of fetal abnormalities in the LDA group was found to be 3.3% and the rate of fetal abnormalities in the control group was found to be 2.8%, this difference was not significant (P=0.421). Many of these patients also started taking LDA in their first trimester which is a critical time for most congenital anomalies, suggesting that even at the most critical period there is no significant negative impact from the use of LDA. This study did find that previous spontaneous abortions (OR = 1.15, 95% CI: 1.01–1.31, P = 0.040) and a history of fetal malformations (OR = 3.22, 95% CI: 1.12–9.20, P = 0.029) were associated with a risk of fetal congenital abnormalities. This study was done in the Chinese population, thus further studies on the effects of LDA in different ethnic populations are needed to generalize these results. Congenital anomalies are thought to have a multifactorial and complex pathogenesis, with two of the factors found by this study to be a history of fetal abnormalities and a history of spontaneous abortions. This study does show however, that in the Chinese population LDA was not found to be associated with congenital anomalies and is likely safe to use in pregnancy for prophylaxis and treatment of other conditions.
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