Authors of a recent Cochrane review concluded that low-dose aspirin treatment of 1,000 pregnant women at risk of developing preeclampsia resulted in 16 fewer cases of preeclampsia, 16 fewer preterm births, 7 fewer cases of small-for-gestational age newborns, and 5 fewer fetal or neonatal deaths.1
The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend treatment with 81 mg of aspirin daily, initiated before 16 weeks of pregnancy to prevent preeclampsia in women with one major risk factor (personal history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal or autoimmune disease) or at least two moderate risk factors (nulliparity; obesity; mother or sister with preeclampsia; a sociodemographic characteristic such as African American race or low socioeconomic status; age ≥35 years; personal history factors such as prior low birth weight infant, previous adverse pregnancy outcome, or >10-year interpregnancy interval).2,3 Healthy pregnant women with a previous uncomplicated full-term delivery do not need treatment with low-dose aspirin.2,3
However, evolving data and expert opinion suggest that expanding the indications for aspirin treatment and increasing the recommended dose of aspirin may be warranted.
Nulliparity
Nulliparity is the single clinical characteristic that is associated with the greatest number of cases of preeclampsia.4 Hence, from a public health perspective, reducing the rate of preeclampsia among nulliparous women is a top priority.
ACOG and USPSTF do not recommend aspirin treatment for all nulliparous women because risk factors help to identify those nulliparous women who benefit from aspirin treatment.
However, a recent cost-effectiveness analysis compared the health care costs and rates of preeclampsia for 4 prevention strategies among all pregnant women in the United States (nulliparous and parous)5:
- no aspirin use
- use of aspirin based on biomarker and ultrasound measurements
- use of aspirin based on USPSTF guidelines for identifying women at risk
- prescription of aspirin to all pregnant women.
Health care costs and rates of preeclampsia were lowest with the universal prescription of aspirin to all pregnant women in the United States. Compared with universal prescription of aspirin, the USPSTF approach, the biomarker-ultrasound approach, and the no aspirin approach were associated with 346, 308, and 762 additional cases of preeclampsia per 100,000 women. In sensitivity analyses, universal aspirin was the optimal strategy under most assumptions.
Another cost effectiveness analysis concluded that among nulliparous pregnant women, universal aspirin treatment was superior to aspirin treatment based on biomarker-ultrasound identification of women at high risk.6
In a recent clinical trial performed in India, Guatemala, Pakistan, Democratic Republic of Congo, Kenya, and Zambia, 14,361 nulliparous women were randomly assigned to placebo or 81 mg of aspirin daily between 6 and 14 weeks of gestation.7 Preterm birth (<37 weeks’ gestation) occurred in 13.1% and 11.6% of women treated with placebo or aspirin (relative risk [RR], 0.89; 95% confidence interval [CI], 0.81 to 0.98, P = .012). Most of the decrease in preterm birth appeared to be due to a decrease in the rate of preeclampsia in the aspirin-treated nulliparous women. The investigators also noted that aspirin treatment of nulliparous women resulted in a statistically significant decrease in perinatal mortality (RR, 0.86) and early preterm delivery, <34 weeks’ gestation (RR, 0.75).
Universal prescription of low-dose aspirin to nulliparous women in order to prevent preeclampsia and preterm birth may become recognized as an optimal public health strategy. As a step toward universal prescription of aspirin to nulliparous women, an opt-out rather than a screen-in strategy might be considered.8
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