USPSTF recommends low-dose aspirin for preeclampsia prevention

The use of low-dose aspirin is advisable after 12 weeks of gestation in asymptomatic pregnant women at high risk for developing preeclampsia, according to a recommendation from the U.S. Preventive Services Task Force.

The recommendation, published online Sept. 8 in the Annals of Internal Medicine, is based on a review of new evidence suggesting that the net benefit of low-dose aspirin for preventing preeclampsia is of substantial magnitude. It updates a 1996 recommendation from the USPSTF, which concluded that there was insufficient evidence at that time to recommend for or against the routine use of aspirin for the prevention of preeclampsia.

Louise Koenig/Frontline Medical News

The current evidence – including 15 randomized controlled trials used to assess the health benefits of low-dose aspirin, 13 randomized controlled trials used to evaluate preeclampsia incidence, and 19 randomized controlled trials and 2 good-quality observational studies used to evaluate harms associated with low-dose aspirin use – suggests that women at risk may benefit from low-dose aspirin beginning after 12 weeks of gestation.

Preeclampsia complicates 2%-8% of pregnancies worldwide, and accounts for 15% of preterm births and 12% of maternal deaths in the United States, according to the task force.

"The USPSTF found adequate evidence of a reduction in risk for preeclampsia, preterm birth, and IUGR [intrauterine growth restriction] in women at increased risk for preeclampsia who received low-dose aspirin, thus demonstrating substantial benefit. Low-dose aspirin (range, 60-150 mg/day) reduced the risk for preeclampsia by 24% in clinical trials [pooled relative risk, 0.76] and reduced the risk for preterm birth by 14% and IUGR by 20% [pooled relative risk, 0.86 and 0.80, respectively]," the updated recommendation stated (Ann. Intern. Med. 2014 Sept. 8 [doi:10.7326/m14-1884]).

Adequate evidence also indicates that low-dose aspirin is not associated with any increase in the risk of placental abruption, postpartum hemorrhage, fetal intracranial bleeding, or perinatal mortality.

"Evidence on long-term outcomes in offspring exposed in utero to low-dose aspirin is limited, but no developmental harms were identified by age 18 months in the one study reviewed," the task force wrote, concluding – with moderate certainty – that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, and IUGR in women at high risk.

The decision to initiate low-dose aspirin therapy in this population is typically based on medical history; there are no validated methods for identifying women at high risk based on biomarkers, clinical diagnostic tests, or medical history. However, as part of the recommendation, the USPSTF provided a pragmatic approach that may help identify those at risk.

"Women with one or more risk factors should receive low-dose aspirin. Women with several moderate risk factors may also benefit from low-dose aspirin," the task force noted, adding that the evidence for the latter approach is less certain, and that clinicians should use clinical judgment and discuss the risks and benefits with patients.

The recommendation applies to asymptomatic women at risk in whom low-dose aspirin is not contraindicated, and defines women at high risk as those with a history of preeclampsia, especially those with an adverse outcome; chronic hypertension, renal disease, type 1 or 2 diabetes, or an autoimmune disease; and those with multifetal gestation, according to the updated recommendation.

Moderate risk factors include nulliparity, obesity, a family history of preeclampsia, age greater than or equal to 35 years, African American race, low socioeconomic status, low birth rate or small for gestational age, greater than 10-year pregnancy interval, or previous adverse pregnancy outcome.

As for appropriate dosing, the most common dosage across studies was 100 mg, but the two largest trials contributing to benefit estimates used 60 mg.

An 81-mg dose was not specifically evaluated, but is commonly available in the United States in tablet form, and is a reasonable dosage for preeclampsia prophylaxis, the task force said.

The updated recommendation is generally in keeping with those of other organizations, including the American College of Obstetricians and Gynecologists, the World Health Organization, the National Institute for Health and Clinical Excellence, the American Heart Association/American Stroke Association, and the American Academy of Family Physicians. For example, ACOG recommends initiating daily low-dose aspirin during the late first trimester in those with a history of early-onset preeclampsia and preterm delivery, or with a history of preeclampsia in more than one prior pregnancy (<cf number="\"2\"">“</cf>American College of Obstetricians and Gynecologists: Hypertension in Pregnancy [Washington, D.C.: American College of Obstetricians and Gynecologists, 2013]), and WHO recommends daily low-dose aspirin as early as 12 weeks for those at high risk ("WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia" [Geneva: World Health Organization, 2011]).

The review by the USPSTF identified several research needs. For example, additional study is needed on the effects of low-dose aspirin on the development of preeclampsia and how patient response is affected by various risk factors. Research is also needed on how to improve clinicians’ ability to identify those at risk, and particularly those who would benefit most from prophylaxis. Study is needed on risk assessment tools, and on populations at particular risk, such as African American and nulliparous women.

Future trials should recruit adequate numbers of women from racial/ethnic populations that are at disproportionate risk.

"Larger studies on aspirin use in the first or early second trimester may improve the evidence base on optimal timing of low-dose aspirin preventive medication. Other areas of research include optimal therapies that individualize the aspirin dosage and timing of administration (e.g., morning vs. bedtime)," they concluded, noting that research is also needed to explore less-well-established risk factors, and to investigate whether preeclampsia prevention with low-dose aspirin affects long-term risk for cardiovascular disease, and whether there is any benefit to continuing low-dose aspirin after delivery in those at high risk.

The use of low-dose aspirin is advisable after 12 weeks of gestation in asymptomatic pregnant women at high risk for developing preeclampsia, according to a recommendation from the U.S. Preventive Services Task Force.

The recommendation, published online Sept. 8 in the Annals of Internal Medicine, is based on a review of new evidence suggesting that the net benefit of low-dose aspirin for preventing preeclampsia is of substantial magnitude. It updates a 1996 recommendation from the USPSTF, which concluded that there was insufficient evidence at that time to recommend for or against the routine use of aspirin for the prevention of preeclampsia.

Louise Koenig/Frontline Medical News

The current evidence – including 15 randomized controlled trials used to assess the health benefits of low-dose aspirin, 13 randomized controlled trials used to evaluate preeclampsia incidence, and 19 randomized controlled trials and 2 good-quality observational studies used to evaluate harms associated with low-dose aspirin use – suggests that women at risk may benefit from low-dose aspirin beginning after 12 weeks of gestation.

Preeclampsia complicates 2%-8% of pregnancies worldwide, and accounts for 15% of preterm births and 12% of maternal deaths in the United States, according to the task force.

"The USPSTF found adequate evidence of a reduction in risk for preeclampsia, preterm birth, and IUGR [intrauterine growth restriction] in women at increased risk for preeclampsia who received low-dose aspirin, thus demonstrating substantial benefit. Low-dose aspirin (range, 60-150 mg/day) reduced the risk for preeclampsia by 24% in clinical trials [pooled relative risk, 0.76] and reduced the risk for preterm birth by 14% and IUGR by 20% [pooled relative risk, 0.86 and 0.80, respectively]," the updated recommendation stated (Ann. Intern. Med. 2014 Sept. 8 [doi:10.7326/m14-1884]).

Adequate evidence also indicates that low-dose aspirin is not associated with any increase in the risk of placental abruption, postpartum hemorrhage, fetal intracranial bleeding, or perinatal mortality.

"Evidence on long-term outcomes in offspring exposed in utero to low-dose aspirin is limited, but no developmental harms were identified by age 18 months in the one study reviewed," the task force wrote, concluding – with moderate certainty – that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, and IUGR in women at high risk.

The decision to initiate low-dose aspirin therapy in this population is typically based on medical history; there are no validated methods for identifying women at high risk based on biomarkers, clinical diagnostic tests, or medical history. However, as part of the recommendation, the USPSTF provided a pragmatic approach that may help identify those at risk.

"Women with one or more risk factors should receive low-dose aspirin. Women with several moderate risk factors may also benefit from low-dose aspirin," the task force noted, adding that the evidence for the latter approach is less certain, and that clinicians should use clinical judgment and discuss the risks and benefits with patients.

The recommendation applies to asymptomatic women at risk in whom low-dose aspirin is not contraindicated, and defines women at high risk as those with a history of preeclampsia, especially those with an adverse outcome; chronic hypertension, renal disease, type 1 or 2 diabetes, or an autoimmune disease; and those with multifetal gestation, according to the updated recommendation.

Moderate risk factors include nulliparity, obesity, a family history of preeclampsia, age greater than or equal to 35 years, African American race, low socioeconomic status, low birth rate or small for gestational age, greater than 10-year pregnancy interval, or previous adverse pregnancy outcome.

As for appropriate dosing, the most common dosage across studies was 100 mg, but the two largest trials contributing to benefit estimates used 60 mg.

An 81-mg dose was not specifically evaluated, but is commonly available in the United States in tablet form, and is a reasonable dosage for preeclampsia prophylaxis, the task force said.

The updated recommendation is generally in keeping with those of other organizations, including the American College of Obstetricians and Gynecologists, the World Health Organization, the National Institute for Health and Clinical Excellence, the American Heart Association/American Stroke Association, and the American Academy of Family Physicians. For example, ACOG recommends initiating daily low-dose aspirin during the late first trimester in those with a history of early-onset preeclampsia and preterm delivery, or with a history of preeclampsia in more than one prior pregnancy (<cf number="\"2\"">“</cf>American College of Obstetricians and Gynecologists: Hypertension in Pregnancy [Washington, D.C.: American College of Obstetricians and Gynecologists, 2013]), and WHO recommends daily low-dose aspirin as early as 12 weeks for those at high risk ("WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia" [Geneva: World Health Organization, 2011]).

The review by the USPSTF identified several research needs. For example, additional study is needed on the effects of low-dose aspirin on the development of preeclampsia and how patient response is affected by various risk factors. Research is also needed on how to improve clinicians’ ability to identify those at risk, and particularly those who would benefit most from prophylaxis. Study is needed on risk assessment tools, and on populations at particular risk, such as African American and nulliparous women.

Future trials should recruit adequate numbers of women from racial/ethnic populations that are at disproportionate risk.

"Larger studies on aspirin use in the first or early second trimester may improve the evidence base on optimal timing of low-dose aspirin preventive medication. Other areas of research include optimal therapies that individualize the aspirin dosage and timing of administration (e.g., morning vs. bedtime)," they concluded, noting that research is also needed to explore less-well-established risk factors, and to investigate whether preeclampsia prevention with low-dose aspirin affects long-term risk for cardiovascular disease, and whether there is any benefit to continuing low-dose aspirin after delivery in those at high risk.

The use of low-dose aspirin is advisable after 12 weeks of gestation in asymptomatic pregnant women at high risk for developing preeclampsia, according to a recommendation from the U.S. Preventive Services Task Force.

The recommendation, published online Sept. 8 in the Annals of Internal Medicine, is based on a review of new evidence suggesting that the net benefit of low-dose aspirin for preventing preeclampsia is of substantial magnitude. It updates a 1996 recommendation from the USPSTF, which concluded that there was insufficient evidence at that time to recommend for or against the routine use of aspirin for the prevention of preeclampsia.

Louise Koenig/Frontline Medical News

The current evidence – including 15 randomized controlled trials used to assess the health benefits of low-dose aspirin, 13 randomized controlled trials used to evaluate preeclampsia incidence, and 19 randomized controlled trials and 2 good-quality observational studies used to evaluate harms associated with low-dose aspirin use – suggests that women at risk may benefit from low-dose aspirin beginning after 12 weeks of gestation.

Preeclampsia complicates 2%-8% of pregnancies worldwide, and accounts for 15% of preterm births and 12% of maternal deaths in the United States, according to the task force.

"The USPSTF found adequate evidence of a reduction in risk for preeclampsia, preterm birth, and IUGR [intrauterine growth restriction] in women at increased risk for preeclampsia who received low-dose aspirin, thus demonstrating substantial benefit. Low-dose aspirin (range, 60-150 mg/day) reduced the risk for preeclampsia by 24% in clinical trials [pooled relative risk, 0.76] and reduced the risk for preterm birth by 14% and IUGR by 20% [pooled relative risk, 0.86 and 0.80, respectively]," the updated recommendation stated (Ann. Intern. Med. 2014 Sept. 8 [doi:10.7326/m14-1884]).

Adequate evidence also indicates that low-dose aspirin is not associated with any increase in the risk of placental abruption, postpartum hemorrhage, fetal intracranial bleeding, or perinatal mortality.

"Evidence on long-term outcomes in offspring exposed in utero to low-dose aspirin is limited, but no developmental harms were identified by age 18 months in the one study reviewed," the task force wrote, concluding – with moderate certainty – that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, and IUGR in women at high risk.

The decision to initiate low-dose aspirin therapy in this population is typically based on medical history; there are no validated methods for identifying women at high risk based on biomarkers, clinical diagnostic tests, or medical history. However, as part of the recommendation, the USPSTF provided a pragmatic approach that may help identify those at risk.

"Women with one or more risk factors should receive low-dose aspirin. Women with several moderate risk factors may also benefit from low-dose aspirin," the task force noted, adding that the evidence for the latter approach is less certain, and that clinicians should use clinical judgment and discuss the risks and benefits with patients.

The recommendation applies to asymptomatic women at risk in whom low-dose aspirin is not contraindicated, and defines women at high risk as those with a history of preeclampsia, especially those with an adverse outcome; chronic hypertension, renal disease, type 1 or 2 diabetes, or an autoimmune disease; and those with multifetal gestation, according to the updated recommendation.

Moderate risk factors include nulliparity, obesity, a family history of preeclampsia, age greater than or equal to 35 years, African American race, low socioeconomic status, low birth rate or small for gestational age, greater than 10-year pregnancy interval, or previous adverse pregnancy outcome.

As for appropriate dosing, the most common dosage across studies was 100 mg, but the two largest trials contributing to benefit estimates used 60 mg.

An 81-mg dose was not specifically evaluated, but is commonly available in the United States in tablet form, and is a reasonable dosage for preeclampsia prophylaxis, the task force said.

The updated recommendation is generally in keeping with those of other organizations, including the American College of Obstetricians and Gynecologists, the World Health Organization, the National Institute for Health and Clinical Excellence, the American Heart Association/American Stroke Association, and the American Academy of Family Physicians. For example, ACOG recommends initiating daily low-dose aspirin during the late first trimester in those with a history of early-onset preeclampsia and preterm delivery, or with a history of preeclampsia in more than one prior pregnancy (<cf number="\"2\"">“</cf>American College of Obstetricians and Gynecologists: Hypertension in Pregnancy [Washington, D.C.: American College of Obstetricians and Gynecologists, 2013]), and WHO recommends daily low-dose aspirin as early as 12 weeks for those at high risk ("WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia" [Geneva: World Health Organization, 2011]).

The review by the USPSTF identified several research needs. For example, additional study is needed on the effects of low-dose aspirin on the development of preeclampsia and how patient response is affected by various risk factors. Research is also needed on how to improve clinicians’ ability to identify those at risk, and particularly those who would benefit most from prophylaxis. Study is needed on risk assessment tools, and on populations at particular risk, such as African American and nulliparous women.

Future trials should recruit adequate numbers of women from racial/ethnic populations that are at disproportionate risk.

"Larger studies on aspirin use in the first or early second trimester may improve the evidence base on optimal timing of low-dose aspirin preventive medication. Other areas of research include optimal therapies that individualize the aspirin dosage and timing of administration (e.g., morning vs. bedtime)," they concluded, noting that research is also needed to explore less-well-established risk factors, and to investigate whether preeclampsia prevention with low-dose aspirin affects long-term risk for cardiovascular disease, and whether there is any benefit to continuing low-dose aspirin after delivery in those at high risk.