Low-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Henderson, Jillian T. PhD, MPH
Whitlock, Evelyn P. MD, MPH
O'Connor, Elizabeth PhD
Senger, Caitlyn A. MPH
Thompson, Jamie H. MPH
Rowland, Maya G. MPH

From Kaiser Permanente Northwest, Portland, Oregon.

Note: This review was conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center under contract to AHRQ. AHRQ staff provided oversight for the project and assisted in the external review of the companion draft evidence synthesis.

Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by AHRQ or the U.S. Department of Health and Human Services.

Acknowledgment: The authors thank the AHRQ staff; members of the USPSTF; James M. Roberts, MD, Lisa M. Askie, MD, Emmanuel Bujold, MD, MSc, Aaron B. Caughey, MD, MPH, Maurice Druzin, MD, Ramon Hermida, PhD, Baha M. Sibai, MD, Helen J. Barr, MD, Yuling Hong, MD, PhD, MSc, Uma M. Reddy, MD, MPH, Caroline Signore, MD, MPH, and Catherine Y. Sprong, MD, for providing expert and federal partner review of the report; and Carrie Patnode, Kevin Lutz, Smyth Lai, and Keshia Bigler at the Kaiser Permanente Center for Health Research.

Financial Support: By contract HHS-290-2012-00015-I, task order 3, from AHRQ.

Disclosures: Dr. Whitlock reports being paid by contract to conduct the systematic review independently for use by the U.S. Preventive Services Task Force. Dr. O'Connor reports grants from the Agency for Healthcare Research and Quality during the conduct of the study. Ms. Senger reports grants from the Agency for Healthcare Research and Quality during the conduct of the study. Ms. Rowland reports grants from the Agency for Healthcare Research and Quality outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2844.

Requests for Single Reprints: Reprints are available from the AHRQ Web site (www.ahrq.gov).

Current author addresses and author contributions are available at www.annals.org.

For author affiliations, see end of text.

This article was published online first at www.annals.org on 8 April 2014.

Current Author Addresses: Drs. Henderson, Whitlock, and O'Connor; Ms. Senger; Ms. Thompson; and Ms. Rowland: Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227.

Author Contributions: Conception and design: J.T. Henderson, E.P. Whitlock.

Analysis and interpretation of the data: J.T. Henderson, E.P. Whitlock, E. O'Connor, C.A. Senger, J.H. Thompson.

Drafting of the article: J.T. Henderson, E.P. Whitlock.

Critical revision of the article for important intellectual content: J.T. Henderson, E.P. Whitlock, E. O'Connor, C.A. Senger, J.H. Thompson.

Final approval of the article: J.T. Henderson, E.P. Whitlock, E. O'Connor, C.A. Senger, J.H. Thompson, M.G. Rowland.

Provision of study materials or patients: C.A. Senger, J.H. Thompson, M.G. Rowland.

Statistical expertise: E. O'Connor.

Obtaining of funding: E.P. Whitlock.

Administrative, technical, or logistic support: C.A. Senger, J.H. Thompson, M.G. Rowland.

Collection and assembly of data: C.A. Senger, J.H. Thompson, M.G. Rowland.

Annals of Internal Medicine 160(10):p 695-703, May 20, 2014.

Background:

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality.

Purpose:

To systematically review benefits and harms of low-dose aspirin for preventing morbidity and mortality from preeclampsia.

Data Sources:

MEDLINE, Database of Abstracts of Reviews of Effects, PubMed, and Cochrane Central Register of Controlled Trials (January 2006 to June 2013); previous systematic reviews, clinical trial registries, and surveillance searches for large studies (June 2013 to February 2014).

Study Selection:

Randomized, controlled trials (RCTs) to assess benefits among women at high preeclampsia risk and RCTs or large cohort studies of harms among women at any risk level. English-language studies of fair or good quality were included.

Data Extraction:

Dual quality assessment and abstraction of studies.

Data Synthesis:

Two large, multisite RCTs and 13 smaller RCTs of high-risk women (8 good-quality) were included, in addition to 6 RCTs and 2 observational studies of average-risk women to assess harms (7 good-quality). Depending on baseline risk, aspirin use was associated with absolute risk reductions of 2% to 5% for preeclampsia (relative risk [RR], 0.76 [95% CI, 0.62 to 0.95]), 1% to 5% for intrauterine growth restriction (RR, 0.80 [CI, 0.65 to 0.99]), and 2% to 4% for preterm birth (RR, 0.86 [CI, 0.76 to 0.98]). No significant perinatal or maternal harms were identified, but rare harms could not be ruled out. Evidence on long-term outcomes was sparse, but 18-month follow-up from the largest trial found no developmental harms.

Limitations:

Benefits may have been overestimated due to small-study effects. Predictive intervals were not statistically significant. Future studies could shift findings toward the null.

Conclusion:

Daily low-dose aspirin beginning as early as the second trimester prevented clinically important health outcomes. No harms were identified, but long-term evidence was limited.

Primary Funding Source:

Agency for Healthcare Research and Quality.