Note: This draft Recommendation Statement is not the final recommendation of the U.S. Preventive Services Task Force. This draft is distributed solely for the purpose of pre-release review. It has not been disseminated otherwise by the USPSTF. It does not represent and should not be interpreted to represent a USPSTF determination or policy.
This draft Recommendation Statement is based on an evidence review that was published on April 8, 2014 (available at http://www.uspreventiveservicestaskforce.org/uspstf14/asprpreg/asprpregart.htm).
The USPSTF makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decisionmaking to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
This draft Recommendation Statement is available for comment from April 8 until May 5, 2014 at 5:00 PM ET. You may wish to read the entire Recommendation Statement before you comment. A fact sheet that explains the draft recommendations in plain language is available here.
Low-Dose Aspirin for the Prevention of Morbidity and Mortality From Preeclampsia: U.S. Preventive Services Task Force Recommendation Statement
Summary of Recommendation and Evidence
The U.S. Preventive Services Task Force (USPSTF) recommends low-dose aspirin (81 mg/day) preventive medication after 12 weeks’ gestation in women who are at high risk for preeclampsia.
This is a B recommendation.
See the Clinical Considerations section for additional information about risk factors, timing, and dosage.
Preeclampsia is one of the most serious health problems affecting pregnant women in the world. It is a complication in 2% to 8% of pregnancies worldwide and contributes to both maternal and infant morbidity and mortality. Preeclampsia also accounts for 15% of preterm births in the United States (1). The disorder is defined by the onset of hypertension (blood pressure of >140/90 mm Hg) and proteinuria (presence of ≥0.3 g of protein in the urine within a 24-hour period) during the second half of pregnancy (>20 weeks). In the absence of proteinuria, preeclampsia is classified as hypertension with any of the following: thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or cerebral or visual disturbances (2).
Recognition of Risk Status
Important risk factors for preeclampsia include preeclampsia in a previous pregnancy (including early-onset preeclampsia), intrauterine growth restriction (IUGR) in a previous pregnancy, preterm birth, placental abruption or fetal death, maternal comorbid conditions (including type 1 or 2 pregestational diabetes, chronic hypertension, renal disease, and autoimmune diseases), and multifetal gestation (1).
Predictive models that combine several risk factors to identify women who will develop preeclampsia, such as serum biomarkers, uterine artery Doppler ultrasonography, and clinical history and measures, are in development (3, 4). None have yet shown sufficient accuracy for clinical use.
Benefits of Preventive Medication
The USPSTF found adequate evidence of a reduction in preeclampsia, preterm birth, and IUGR in women at increased risk for preeclampsia who received low-dose aspirin, thus demonstrating substantial benefit.
Low-dose aspirin (range, 50 to 160 mg/day) reduced the risk for preeclampsia by 24% in clinical trials. It also reduced the risk for preterm birth by 14% and IUGR by 20%.
Harms of Preventive Medication
The USPSTF found adequate evidence that low-dose aspirin preventive medication does not increase the risk for placental abruption, postpartum hemorrhage, or fetal intracranial bleeding. In a meta-analysis of randomized, controlled trials (RCTs) and observational studies of women at low/average or increased risk for preeclampsia, there was no significantly increased risk for these adverse events. In addition, there was no difference in the risk for placental abruption by aspirin dosage.
The USPSTF also found adequate evidence that low-dose aspirin preventive medication in women at increased risk for preeclampsia does not increase the risk for perinatal mortality.
Evidence on long-term outcomes in offspring exposed to low-dose aspirin during pregnancy is limited, but no developmental harms were identified by age 18 months in the one study reviewed.
The USPSTF concludes that the harms of low-dose aspirin use in pregnancy are no greater than small.
The USPSTF concludes 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 for preeclampsia.
Patient Population Under Consideration
This recommendation applies to asymptomatic pregnant women who are at increased risk for preeclampsia and who have no prior adverse effects with or contraindications to low-dose aspirin use.
Assessment of Risk for Preeclampsia
There are no validated methods of identifying women at high risk for preeclampsia based on biomarkers, clinical diagnostic tests, or medical history. Most clinicians use medical history to identify women at high risk. These risk factors, based on medical history, can help guide clinicians and their patients in the decision to begin aspirin use.
While clinical risk assessments were not systematically reviewed for this recommendation, a pragmatic approach is described in Table 1. This approach may help identify a patient population with an absolute risk for preeclampsia of at least 8%, which is consistent with the lowest preeclampsia incidence observed in the control group of studies examining aspirin benefits that were included in the USPSTF evidence review (1). Women with one or more high-risk factors should receive low-dose aspirin. Women with several moderate risk factors may also benefit from low-dose aspirin (Table 1). Clinicians should use clinical judgment in assessing preeclampsia risk in their patient population.
Table 1. Preeclampsia Risk Factors Based on Patient Medical History*
|Level of Risk||Risk Factors||Aspirin|
Single risk factors consistently associated with the greatest risk for preeclampsia
||Low-dose aspirin if ≥1 high-risk factors exist|
Presence of multiple moderate risk factors may be used by clinicians to identify women at high risk for preeclampsia
||Low-dose aspirin if several moderate risk factors exist|
|Low risk||Prior uncomplicated term delivery||No aspirin|
* Includes only risk factors that can be obtained from the patient medical history. Clinical measures, such as uterine artery Doppler ultrasonography, are not included.
** Preeclampsia incidence rates would be expected to be approximately ≥8% in pregnant women with ≥1 of these risk factors (1, 5).
† These risk factors are independently associated with moderate preeclampsia risk, some more consistently than others (1).
Assessment of Risk for Adverse Effects
Low-dose aspirin use in women at increased risk for preeclampsia has not been shown to increase the occurrence of placental abruption, postpartum hemorrhage, or fetal harms, such as intracranial bleeding and congenital anomalies.
Use of Preventive Medication
The dosage and timing of initiation of low-dose aspirin varies across studies. However, the beneficial effects and small harms of low-dose aspirin use are consistent across dosages and timing of initiation. It was not possible to determine from the evidence whether a specific dosage or timing of aspirin use conferred greater benefit over other dosages or timing intervals.
Low-dose aspirin use at dosages between 50 and 160 mg has been shown to reduce the occurrence of preeclampsia, preterm birth, and IUGR in women at increased risk for preeclampsia in several randomized trials (1). The most commonly used dosage was 100 mg, but the two largest trials contributing to the estimates of benefit used 60 mg (1, 6, 7). In the United States, low-dose aspirin is available as 81-mg tablets, which is a reasonable dosage for prophylaxis for women at high risk for preeclampsia.
In 15 RCTs, low-dose aspirin was initiated between 12 and 28 weeks' gestation. None of the trials initiated aspirin before 12 weeks. Eight trials initiated low-dose aspirin before 16 weeks' gestation. Evidence did not suggest additional benefit when starting aspirin earlier (12 to 16 weeks) rather than later (≥16 weeks) in pregnancy in women at increased risk for preeclampsia (1).
Research Needs and Gaps
Research to improve our understanding of the effect of low-dose aspirin on the development of preeclampsia and how the magnitude of response to low-dose aspirin may vary with individual or combinations of risk factors for preeclampsia is needed. Research to improve clinicians' ability to identify women at increased risk for preeclampsia, particularly those who would receive the greatest benefit from aspirin preventive medication, is also needed. Efforts to validate the effectiveness of risk assessment tools using clinical history alone or combined with clinical testing hope to better identify high-risk women so that aspirin preventive medication can help reduce the incidence of preeclampsia and its consequent outcomes.
Further research in populations that bear the highest disease burden for preeclampsia, including African American and nulliparous women, who may be at highest risk, is needed. Multivariable risk prediction models that identify healthy nulliparous women who are likely to develop preeclampsia are being developed and tested, but further refinement and validation are needed. Future trials should recruit adequate numbers of women from racial/ethnic populations that are at disproportionate risk, such as African American women, in order to have sufficient power to determine the effectiveness of different aspirin dosages and timing of initiation in these high-risk groups.
Larger studies investigating aspirin use in the early second trimester may help to 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).
In addition, studies that explore less well-established risk factors that might better identify women at high risk for preeclampsia are needed. Further research should also investigate whether preeclampsia prevention with low-dose aspirin affects women's long-term risk for cardiovascular disease and whether there are benefits to continuing low-dose aspirin after delivery in women with one or more high-risk factors.
Burden of Disease
Preeclampsia is a multisystem inflammatory syndrome with an unclear etiology and natural history. It is one of the leading causes of maternal and perinatal morbidity and is the second-leading cause of maternal mortality worldwide (1).
In 2010, preeclampsia affected 3.8% of deliveries in the United States (8). The rate of severe preeclampsia has increased over the past three decades. In the United States, 12% of maternal deaths are directly attributable to preeclampsia and eclampsia. However, morbidity is more common than mortality, and it is estimated that more than one third of severe obstetric morbidities are related to preeclampsia (1).
Preeclampsia accounts for 15% of preterm births in the United States and is a leading cause of medically indicated preterm birth. Delivery is the only cure for preeclampsia (1). Early-onset preeclampsia is usually more severe and often requires preterm delivery. Preterm infants (≤37 weeks' gestation) are at increased risk for morbidity and mortality, and complications increase with earlier delivery. Additional important threats to the fetus from preeclampsia include IUGR, being small for gestational age, placental abruption, neonatal intensive care unit admission, and neonatal death. It is estimated that perinatal mortality is about two times higher in pregnancies affected by preeclampsia (1).
There are racial/ethnic disparities in the prevalence of and mortality from preeclampsia. NonHispanic black women are at greater risk for developing preeclampsia and bear a greater burden of maternal and infant morbidity and perinatal mortality. In the United States, maternal death from preeclampsia is higher in nonHispanic black women than in nonHispanic white women. Disparities in risk factors for preeclampsia, limited access to early prenatal care, and obstetrical interventions may account for some of the differences seen in prevalence and clinical outcomes (1).
Scope of Review
In 1996, the USPSTF reviewed the effectiveness of low-dose aspirin use to prevent preeclampsia (9). The current systematic review focused on new evidence on the effectiveness of low-dose aspirin in preventing preeclampsia in women at increased risk, decreasing adverse maternal and perinatal health outcomes, and assessing the maternal and fetal harms of low-dose aspirin use during pregnancy.
Effectiveness of Preventive Medication
Fifteen RCTs (eight good-quality) were assessed in the evaluation of maternal and perinatal health benefits. Thirteen RCTs (eight good-quality) were reviewed to evaluate preeclampsia incidence. RCTs of women at increased risk for preeclampsia were used to evaluate benefits. All RCTs were placebo-controlled (1).
Generally, women in the RCTs were young (mean age range, 20.3 to 31 years) and white. Only one RCT of women at increased risk and two RCTs included for harms included majority populations of black women. None of the trials initiated low-dose aspirin before 12 weeks' gestation and eight trials initiated prophylaxis before 16 weeks. The most common discontinuation date was upon delivery, but six RCTs stopped aspirin use before delivery. Aspirin dosages ranged from 60 to 150 mg/day, with the majority of trials using 60 mg (six RCTs) or 100 mg (eight RCTs) (1).
Two large RCTs, the Maternal-Fetal Medicine Units (MFMU) trial and the Collaborative Low-dose Aspirin Study in Pregnancy (CLASP), provided the majority of the data for pooled estimates of benefit (6, 7). The MFMU trial was a U.S. trial conducted at 13 study sites in women at increased risk for preeclampsia (n=2,503). The treatment group received 60 mg of aspirin but was instructed to stop taking the medication if preeclampsia developed. Women were at 13 to 26 weeks' gestation and belonged to one of the following predefined preeclampsia risk categories: pregestational diabetes mellitus (n=471), chronic hypertension (n=744), current multifetal gestation (n=688), or preeclampsia in a prior pregnancy (n=606) (6).
CLASP was a multinational trial (n=9,364) that included 16 sites (such as the United Kingdom, United States, Canada, Germany, Spain, and Hong Kong). Women were enrolled to prevent or treat preeclampsia and IUGR based on medical history. Risk factors for preeclampsia were prior IUGR or preeclampsia, chronic hypertension, renal disease, age, family history of preeclampsia, and multifetal gestation. Women were eligible for study participation if their clinician was unsure whether or not they should receive low-dose aspirin. Two thirds of participants began taking aspirin before 20 weeks' gestation. Low-dose aspirin (60 mg) was continued until delivery (7).
The USPSTF found evidence of a 14% reduction in risk for preterm birth (pooled relative risk [RR], 0.86 [95% CI, 0.76 to 0.98]; k=10; n=11,779; I2=33.2%) in women at increased risk for preeclampsia who were randomized to receive low-dose aspirin. This reduction in preterm birth was because of a decrease in the number of women with preeclampsia, as well as the delay in the development of preeclampsia. Pooled estimates provided evidence of a 20% reduction in IUGR with low-dose aspirin (RR, 0.80 [95% CI, 0.65 to 0.99]; k=13; n=12,504; I2=36.0%) in women at increased risk for preeclampsia. Low-dose aspirin increased the mean birth weight of infants by a pooled weighted mean difference of 130.0 g (95% CI, 36.2 to 223.3; n=10,712; I2=60%). In the pooled analysis (k=10; n=12,240) of aspirin, there was no statistically significant reduction in perinatal mortality (RR, 0.81 [95% CI, 0.65 to 1.01]; I2=0%) in women at increased risk (1).
A pooled estimate of trials reviewed by the USPSTF (k=13; n=12,184) showed a 24% reduction (RR, 0.76 [95% CI, 0.62 to 0.95]) in preeclampsia with low-dose aspirin in women at increased risk. Heterogeneity was moderate across studies (I2=40.5%). Stratified comparisons did not yield evidence that the timing of aspirin initiation (<16 weeks) or dosage had an effect on preeclampsia prevention (1).
Maternal complications of preeclampsia (e.g., HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome, organ system failure, eclampsia, or mortality) rarely occurred in studies and could not be evaluated. Pooled analysis of the Caesarean delivery outcome (k=10 studies; n=10,419) indicated no difference in the Caesarean delivery rate for women taking aspirin compared with placebo (RR, 0.92 [95% CI, 0.79 to 1.08]; I2=24.9%) (1).
The number needed to treat was calculated from the event rate in the trial data at the lowest level of risk for the outcome. The number needed to treat to prevent one diagnosis of preeclampsia was 42 (95% CI, 26 to 200), 71 (95% CI, 41 to 1,429) for IUGR, and 65 (95% CI, 38 to 455) for preterm birth. Absolute risk estimates based on observed event rates ranged from 2% to 5% for preeclampsia, 1% to 5% for IUGR, and 2% to 4% for preterm birth (1).
Potential Harms of Preventive Medication
Nineteen RCTs (12 good-quality) and two good-quality observational studies were assessed to evaluate maternal, perinatal, and developmental harms. Studies of low- or average-risk pregnant women were added to the trials of women at increased risk to evaluate harms (1).
Low-dose aspirin use appears to have no short-term harms during pregnancy. Eleven RCTs (n=23,332) reported on the outcome of placental abruption (six trials in women with increased preeclampsia risk and five trials in women with low/average risk). Pooled analyses showed no statistically significant increase in abruption associated with aspirin (RR, 1.17 [95% CI, 0.93 to 1.48]; I2=36.4%).
Eighteen trials reported on perinatal mortality (with four smaller studies reporting no events). Pooled analyses (k=14; n=22,848) on perinatal mortality (RR, 0.92 [95% CI, 0.76 to 1.11]; I2=0%) suggested no harm from low-dose aspirin. When limited to women at increased risk for preeclampsia, the estimate approached statistical significance for a benefit (RR, 0.81 [95% CI, 0.65 to 1.01]; k=10; n=12,240; I2=0%) (1).
Nine trials (n=22,760) (six trials in women with increased preeclampsia risk and three trials in women with low risk) reported on postpartum hemorrhage. There was no evidence of a treatment effect (RR, 1.02 [95% CI, 0.96 to 1.09]). Five trials (one good-quality) (n=2,748) reported mean blood loss. No evidence demonstrated that low-dose aspirin affected mean blood loss. Studies found slightly lower mean blood loss or equivalent amounts of blood loss between study groups (1).
The pooled relative risk for intracranial hemorrhage in neonates (k=6; n=22,158) was 0.84 (95% CI, 0.61 to 1.16), with low heterogeneity (I2=27.1%; p=0.23). Maternal mortality was a rare outcome and could not be evaluated (1).
Limited evidence was found on long-term outcomes from in utero low-dose aspirin exposure for offspring. One observational study of birth defects resulting from aspirin exposure showed that the rate of cryptorchidism did not differ in male infants exposed and unexposed to aspirin in utero (10). Another observational study on aspirin use during pregnancy had null findings for miscarriage (11). Followup data from the largest trial, CLASP, reported no differences in physical or mental developmental outcomes (e.g., gross motor development, height, weight, or hospital visits) of infants at age 18 months (12).
Adverse events were reported in seven trials; however, most of the events were determined to be unrelated to treatment. Two studies reported women withdrawing from treatment because of itching of the throat and epigastric pain (1).
Estimate of Magnitude of Net Benefit
The USPSTF found adequate evidence that daily low-dose aspirin use in women at high risk for preeclampsia is associated with improved health outcomes through the reduction of preeclampsia, preterm birth, and IUGR. The USPSTF found adequate evidence that low-dose aspirin use does not increase the risk for placental abruption, postpartum hemorrhage, fetal intracranial bleeding, or perinatal mortality. No evidence of harms on long-term outcomes in offspring was identified; however, evidence was limited. Overall, the harms of low-dose aspirin use in pregnancy are considered to be no greater than small.
Therefore, the USPSTF concludes with moderate certainty that the magnitude of net benefit from low-dose aspirin use to prevent morbidity and mortality from preeclampsia in women at high risk is substantial.
How Does Evidence Fit With Biological Understanding?
Preeclampsia is a complex, multisystem inflammatory syndrome that can originate from multiple causes. It is thought to evolve from changes in placental development that result in placental ischemia. Poor placental perfusion may produce inflammation and oxidative stress. Preeclampsia may also develop as a result of overactive inflammatory responses to normal placentation. Preexisting inflammatory conditions are also thought to trigger systemic inflammatory and oxidative stress processes. The anti-inflammatory, antiangiogenesis, and antiplatelet properties of low-dose aspirin are believed to account for its effect on prevention of preeclampsia.
Update of Previous USPSTF Recommendation
In 1996, the USPSTF concluded that there was insufficient evidence to recommend for or against the routine use of aspirin for the prevention of preeclampsia or IUGR. Although a significant reduction in preterm birth suggested benefits to infants, there was inadequate evidence that aspirin provided benefits to women at increased risk for preeclampsia. In addition, the studies available at that time indicated that aspirin use was associated with risk for placental abruption. As a result, the USPSTF concluded that the evidence was insufficient to assess the balance of benefits and harms of aspirin use to prevent preeclampsia in pregnant women at increased risk for preeclampsia (9).
This recommendation updates the 1996 recommendation on aspirin use to prevent preeclampsia. It differs from the previous recommendation in that new evidence on the effectiveness and harms of low-dose aspirin on maternal and perinatal health outcomes now allows the USPSTF to recommend low-dose aspirin for women at high risk for preeclampsia. This recommendation also differs from the 1996 recommendation in that it discusses in more detail the issues of defining high preeclampsia risk in pregnant women.
Recommendations of Others
The American College of Obstetricians and Gynecologists recommends initiating daily low-dose aspirin (60 to 80 mg) during the late first trimester to prevent preeclampsia in women with a medical history of early-onset preeclampsia and preterm delivery before 34 weeks' gestation or history of preeclampsia in more than one previous pregnancy (2). The World Health Organization (WHO) recommends daily low-dose aspirin (75 mg) starting as early as 12 to 20 weeks' gestation for high-risk women. WHO defines high risk as having a history of preeclampsia, diabetes, chronic hypertension, renal or autoimmune disease, or multiple pregnancies. Its recommendations state that there is limited evidence regarding the benefits of low-dose aspirin in other subgroups of high-risk women (13). The National Institute for Health and Clinical Excellence recommends that women at high risk for developing preeclampsia (i.e., women with a history of hypertension in a previous pregnancy, chronic kidney disease, autoimmune disease, type 1 or 2 diabetes, or chronic hypertension) take 75 mg of aspirin daily from 12 weeks until delivery. It also recommends that women with more than one moderate risk factor (first pregnancy, age ≥40 years, pregnancy interval of >10 years, body mass index of ≥35 kg/m2, family history of preeclampsia, or multiple pregnancies) take 75 mg of aspirin daily from 12 weeks until delivery (14). The American Heart Association and the American Stroke Association recommend that women with chronic primary or secondary hypertension or previous pregnancy-related hypertension begin low-dose aspirin from 12 weeks until delivery (15).
Table 2: What the Grades Mean and Suggestions for Practice
Table 3: Levels of Certainty Regarding Net Benefit
|Level of Certainty*||Description|
|High||The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies.|
|Moderate||The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.
|Low||The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
More information may allow an estimation of effects on health outcomes.
*The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.
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2. American College of Obstetricians and Gynecologists. Hypertension in Pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013. Accessed at http://www.acog.org/Resources_And_Publications/Task_Force_and_Work_Group_Reports/Hypertension_in_Pregnancy on 25 March 2014.
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5. Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2014 [In press].
6. Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. N Engl J Med. 1993;329(17):1213-18.
7. Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebanoff M, Thom E, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Low-dose aspirin to prevent preeclampsia in women at high risk. N Engl J Med. 1998;338(11):701-5.
8. Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980–2010: age-period-cohort analysis. BMJ. 2013;347:f6564.
9. U.S. Preventive Services Task Force. Aspirin prophylaxis in pregnancy. In: Guide to Clinical Preventive Services. 2nd ed. Washington, DC: U.S. Department of Health and Human Services; 1996.
10. Jensen MS, Rebordosa C, Thulstrup AM, Toft G, Sørensen HT, Bonde JP, et al. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology. 2010;21(6):779-85.
11. Keim SA, Klebanoff MA. Aspirin use and miscarriage risk. Epidemiology. 2006;17(4):435-9.
12. Bower SJ, Harrington KF, Schuchter K, McGirr C, Campbell S. Prediction of pre-eclampsia by abnormal uterine Doppler ultrasound and modification by aspirin. Br J Obstet Gynaecol. 1996;103(7):625-9.
13. World Health Organization. WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia. Geneva, Switzerland: World Health Organization; 2011. Accessed at http://whqlibdoc.who.int/publications/2011/9789241548335_eng.pdf on 25 March 2014.
14. Redman CW. Hypertension in pregnancy: the NICE guidelines. Heart. 2011;97(23):1967-9.
15. Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, et al; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Council for High Blood Pressure Research. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Feb 6. [Epub ahead of print]
AHRQ Publication No. 14-05207-EF-2
Current as of April 2014
U.S. Preventive Services Task Force. Low-Dose Aspirin for the Prevention of Morbidity and Mortality From Preeclampsia: Draft Recommendation Statement. AHRQ Publication No. 14-05207-EF-2. http://www.uspreventiveservicestaskforce.org/draftrec.htm