USPSTF updates guidelines preeclampsia prophylaxis

The US Preventive Services Task Force (USPSTF) has issued a new report supporting prophylaxis with low-dose aspirin (81 mg/d) after 12 weeks’ gestation in women at high risk of preeclampsia. Published in the Annals of Internal Medicine, the recommendation is similar to one from the American Congress of Obstetricians and Gynecologists but the latter specifies 60 to 80 mg/d of aspirin during the late first trimester in women with a history of early-onset preeclampsia and delivery <34 weeks or a history of preeclampsia in more than one previous pregnancy.

The USPSTF recommends administration of low-dose aspirin for women with one or more of the following high-risk factors for preeclampsia: history of preeclampsia, especially when accompanied by an adverse outcome; multifetal gestation; chronic hypertension; type 1 or 2 diabetes; renal disease; and autoimmune disease (i.e., systemic lupus erythematosus, antiphospholipid syndrome)

Based on a review of 13 studies, the USPSTF found a 24% reduction in risk of preeclampsia (pooled risk ratio [RR], 0.79; 95% confidence interval [CI], 0.62 to 0.95) in women at increased risk (n = 12,184) who used low-dose aspirin. Heterogeneity was moderate across studies (I² = 40.5%). Complications of preeclampsia in mothers, such as hemolysis and development of eclampsia, were rare in the studies and couldn’t be evaluated. No difference in cesarean delivery rate was found among women who received low-dose aspirin and those who received a placebo in a pooled analysis of 10 studies (n = 10,419), (RR, 0.92; 95% CI, 0.79 to 1.08; I²= 24.9%).

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In order to prevent one diagnosis of preeclampsia, the researchers found that the number needed to treat was 42 (95% CI, 26 to 200); for intrauterine growth restriction (IUGR), it was 71 (95% CI, 41 to 1429) and for preterm birth, it was 65 (95% CI, 38 to 455). Based on observed event rates, the absolute risk estimates ranged from 3% to 5% for preeclampsia, to 1% to 5% for IUGR, and 2% to 4% for preterm birth. The results from USPSTF’s reviews were consistent overall with findings from a Cochran Collaboration systemic review and the Perinatal Review of International Studies.

When comparing dosage effects, a significant difference was seen with 1 outcome, preterm birth, when using a cut-point of 75 mg/d. A dosage over the cut-point was associated with a greater reduction in risk, but dosage analyses were confounded by an unequal distribution of sample sizes using different dosages because the 2 largest studies used 60 mg/d of aspirin. None of the studies showed evidence of dose-response relationships. 

Regarding the timing of prophylaxis, in 15 trials, low-dose aspirin was given at 12 to 28 weeks’ gestation; in 8 trials it was started before 16 weeks’ gestation. In no studies was the drug begun before 12 weeks’ gestation. In addition, no evidence was found to support the benefit of beginning an aspirin regimen at 12 to 16 weeks versus 16 weeks or later in pregnancy.

To evaluate maternal, perinatal, and developmental harms, the USPSTF reviewed 19 randomized control trials (RCTs), of which 12 were considered good quality, and 2 good-quality observational studies. Overall, they found, low-aspirin does not appear to produce short-term harm during pregnancy. Eleven RCTs (n = 23,332), including 6 with women at increased risk of preeclampsia, looked at the outcome of placental abruption and pooled analyses showed no statistically significant increase in abruption with aspirin (RR, 1.17 [95% CI, 0.93 to 1.48]; I² = 36.4%). Similarly 18 trials (n = 22,848) reporting on perinatal mortality suggest no harm from low-dose aspirin RR, 0.92 [95% CI, 0.76 to 1.11]; 14 studies; I² = 0%). Most of the adverse events reported in the trials were determined to be unrelated to use of the prophylaxis.

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