Contributor: Kacey Eichelberger, MD
Last update: 10/4/2017
Hypertensive disorders of pregnancy affect about 10% of all pregnant women around the world. This group of diseases and conditions includes preeclampsia, eclampsia, gestational hypertension, and chronic hypertension. Hypertensive disorders of pregnancy are an important cause of severe acute morbidity, long-term disability and death among mothers and babies.
The pathogenesis of preeclampsia is only partially understood and is related to disturbances in placentation at the beginning of pregnancy, followed by generalized inflammation and progressive endothelial damage.
Primary prevention of preeclampsia is controversial and the subject of active research, particularly with regard to the use of anti-inflammatory agents and micronutrients including calcium, vitamin D, and antioxidant vitamin C and E supplements. The only definitive treatment for preeclampsia is termination of pregnancy with delivery of the fetus and placenta, though some women with preeclampsia also present with transient aggravation of the disease in the postpartum period.
The primary source of evidence for creation of the WHO recommendations for the prevention and treatment of preeclampsia and eclampsia was a Cochrane review of randomized control trials. The Cochrane review of 60 randomized control trials including 37,720 women was utilized for the recommendations regarding the use of low-dose aspirin for the treatment of preeclampsia in high-risk groups. This review revealed that there was a statistically significant risk reduction in the development of preeclampsia among women who received antiplatelet agents compared with placebo; this reduction risk was shown to be more marked in high-risk groups.
In trials in which the gestational age at recruitment was specified, the above findings were consistent between women who commenced treatment before and after 20 weeks of pregnancy for gestational hypertension, preeclampsia and placental abruption. For fetal, neonatal or infant death, the use of antiplatelet agents was associated with a statistically significant reduction in risk among women who commenced treatment before 20 weeks, although the reduction in risk remain statistically insignificant.
More recent studies listed in the references below suggest that timing of aspirin administration and dose also play an important role in preeclampsia prevention. In an expert editorial commentary from the February 2017 issue of the American Journal of Obstetrics and Gynecology, Drs. Tong, Moi and Walker suggest the following: “The dose-response data in the report of Roberge et al for the outcome of severe preeclampsia looked pretty convincing and suggests that the aspirin dose to prevent preeclampsia should not be less than 100 mg. Until this is assessed in IPD or head-to-head comparative studies, clinicians should prescribe aspirin at a dose of at least 100 mg.”
Given the structural limitations in aspirin dosing in the United States (offered in 81 mg and 325 mg tablets), and until such time as head-to-head dosing studies are conducted, we suggest clinicians consider dosing prophylactic aspirin therapy for eligible women at 162 mg (two 81 mg tablets) daily at bedtime.
To identify eligible women, we continue to recommend use of the USPSTF’s Clinical Risk Assessment for Preeclampsia tool, as pictured below.
- WHO Recommendations for Prevention and Treatment of Preeclampsia and Eclampsia, 2011.
- Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017 Feb;216(2):110-120.e6
- Tong S, Mol BW, Walker SP. Preventing preeclampsia with aspirin: does dose or timing matter? Am J Obstet Gynecol. 2017 Feb;216(2):95-97. doi: 10.1016/j.ajog.2016.12.003.
- https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication. Acccessed on May 23, 2017.