Aspirin use during pregnancy associated with lower risk of preeclampsia and perinatal mortality: US Preventive Services Task Force

1. Daily low-dose aspirin use during pregnancy in individuals at increased risk for preeclampsia was associated with a lower risk of preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality.

2. Pooled data on the safety profile of low-dose aspirin use during pregnancy in the prevention of preeclampsia did not reveal any serious harms.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Preeclampsia is a hypertensive disorder of pregnancy characterized by high blood pressure and signs of end-organ dysfunction, posing significant maternal and infant health risks. In 2014, the US Preventive Services Task Force (USPSTF) recommended the use of low-dose (81mg/d) aspirin starting at 12-weeks’ gestation in asymptomatic pregnant women who are at high risk for preeclampsia to prevent the target disease and its sequelae. This current review of the evidence on the efficacy of aspirin therapy in reducing the risk for preeclampsia and adverse maternal, perinatal, and childhood outcomes, along with potential harms of aspirin use, was conducted by the USPSTF as an update to its current recommendation. The main endpoints of the selected studies included prevalence and incidence of preeclampsia diagnosis, adverse pregnancy health outcomes and complications including eclampsia, perinatal mortality, preterm birth, small for gestational age, and potential bleeding harms or infant/child harms from aspirin exposure. Among 23 randomized clinical trials (RCTs) (N = 26,952), daily low-dose aspirin use during pregnancy in individuals at increased risk for preeclampsia was associated with a lower risk of preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality, without evident harms. Overall, the low to moderate statistical heterogeneity and consistency of effects across a range of outcomes supported the conclusion that low-dose aspirin is effective for preventing preeclampsia and related perinatal morbidity and mortality for individuals at increased risk for preeclampsia. A limitation of this study was that the selection criteria was limited to English-language literature and trials conducted in regions with very high Human Development Index scores and thus reducing the generalizability of the study findings in the general population, particularly internationally.

Click to read the study in JAMA

Click to read an accompany editorial in JAMA

Relevant Reading: Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force

In-Depth [systematic review and meta-analysis]: This systematic review as part of an updated evidence report from the USPSTF included studies from the previous review in 2014 as well as new literature published between January 2013 and May 2020 in MEDLINE, PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Selected studies included RCTs of low-dose aspirin use during pregnancy to prevent preeclampsia among individuals with risk factors as well as studies conducted in general populations to evaluate potential harms. In total, 23 RCTs (N = 26,952) were included, 18 of which were conducted in populations at increased risk of preeclampsia, where aspirin dosages ranged from 50mg/d to 150mg/d. The incidence of preeclampsia in at-risk populations ranged from 4% to 30%. Overall, aspirin use was significantly associated with lower risk of preeclampsia (pooled RR, 0.85 [95%CI, 0.75-0.95]; 16 RCTs [n = 14,093]; I² = 0%), perinatal mortality (pooled RR, 0.79 [95%CI, 0.66-0.96]; 11 RCTs [n = 13,860]; I² = 0%), preterm birth (pooled RR, 0.80 [95%CI, 0.67-0.95]; 13 RCTs [n = 13 619]; I² = 49%), and intrauterine growth restriction (pooled RR, 0.82 [95%CI, 0.68-0.99]; 16 RCTs [n = 14,385]; I² = 41%). Aspirin use was not significantly associated with risk of postpartum hemorrhage (pooled RR, 1.03 [95%CI, 0.94-1.12]; 9 RCTs [n = 23,133]; I2 = 0%) and other bleeding-related harms, or with rare perinatal or longer-term harms. In RCTs with greater than 300 participants, absolute risk reductions for preeclampsia associated with aspirin use ranged from -1% to -6% and were higher in RCTs with lower enrollment. Among 3 RCTs with the highest enrollment, absolute risk reductions for perinatal mortality ranged from 0.5% to 1.1%.

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