CRD summary

Based on available evidence, this good-quality review concluded that daily low-dose aspirin had modest but important benefits for preventing preeclampsia and consequent illness in high-risk women during pregnancy, although rare or long-term harms could not be ruled out. The authors identified uncertainties in the evidence and their carefully considered conclusions are likely to be reliable.

Authors' objectives

To review the benefits and harms of low-dose aspirin for preventing morbidity and mortality from preeclampsia in high-risk women.

Searching

MEDLINE, PubMed, DARE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched for studies published from January 2006 up to June 2013. Reference lists from previous reviews and meta-analyses were searched for additional evidence.

Study selection

Randomised controlled trials (RCTs) that compared aspirin (50mg to 150mg) with placebo or no treatment in women at high risk of preeclampsia were eligible for inclusion in the evaluation of benefits. The evaluation of harms also included RCTs or cohort studies in women at any risk level. All included studies had to be of "fair" or "good" quality and published in English.

Among included studies, reported daily doses of aspirin ranged from 50mg to 150mg; 60mg or 100mg were most commonly used. Among RCTs, the time of treatment initiation ranged from 12 to 28 weeks; treatment stopping time ranged from 34 weeks to delivery. Maternal age ranged from 20.3 to 31 years. Four studies included a UK setting.

Two reviewers selected studies for inclusion, with disagreements resolved by a third reviewer.

Assessment of study quality

Two reviewers independently appraised study quality according to the US Preventative Services Task Force (USPSTF) criteria, with disagreements resolved by discussion or consultation with a third reviewer. The authors stated that NICE methodology checklists and the Newcastle-Ottawa scale were used to supplement the USPSTF criteria.

Data extraction

One reviewer extracted the number of cases of preeclampsia, pre-term birth, inter-uterine growth restriction, perinatal death, and placental abruption. A second reviewer checked this extraction. Disagreements were resolved by discussion or consultation with a third reviewer.

Methods of synthesis

Pooled relative risks with 95% confidence intervals and prediction intervals were calculated for each outcome using either a random-effects model (or fixed-effect model where fewer than 10% of participants had an event). Statistical heterogeneity was detected using Ι² and Χ², and explored using meta-regression and visual inspection of forest plots.

Small-study effects were investigated by examining funnel plots and calculating the Begg or Peter statistics. Sensitivity analyses were also conducted.

Results of the review

Fifteen RCTs (eight good quality) of high-risk women were included in the review, along with six RCTs and two observational studies (seven good quality) of average-risk women to assess harms.

Benefits of low-dose aspirin treatment

Data from 10 trials (12,240 participants) suggested a statistically non-significant reduction in perinatal death (RR 0.81, 95% CI 0.65 to 1.01; Ι²=0%).

Pooled data from 10 trials (11,779 participants) suggested a statistically significant reduction in pre-term birth (RR 0.86, 95% CI 0.76 to 0.98; Ι²=33%).

There was evidence of a statistically significant reduction in inter-uterine growth restriction (RR 0.80, 95% CI 0.65 to 0.99; Ι²=36%) from 13 trials (12,504 participants).

Average birthweight was greater in aspirin treated groups (130g, 95% CI 36.2 to 223.3; Ι²=60%) and preeclampsia was reduced (RR 0.76, 95% CI 0.62 to 0.95; Ι²=41%; 13 trials; 12,184 participants).

There was evidence of small-study effects for pre-term birth, inter-uterine growth restriction and preeclampsia; larger studies reported smaller and statistically non-significant effects. Prediction intervals suggested that future studies could shift statistically significant pooled estimates towards non-significance.

Harms of aspirin treatment

No statistically significant harm for perinatal death, placental abruption, postpartum haemorrhage, mean blood loss, or neonatal intracranial haemorrhage was found. However, event rates were generally low, which increased uncertainty.

Details of sensitivity analyses were reported in the paper.

Authors' conclusions

Available evidence indicated modest but important benefits of daily low-dose aspirin for preventing preeclampsia and consequent illness in high-risk women, although rare or long-term harms could not be ruled out.

CRD commentary

This was a clearly reported systematic review that used appropriate methods to identify, summarise and synthesise data on the benefits and harms of daily-low dose aspirin use for preventing morbidity and mortality from preeclampsia. Inclusion was restricted to higher-quality English language publications, so some potentially relevant data may have been excluded. Efforts were made to minimise reviewer errors and bias throughout the review process.

Limitations in the primary research evidence were identified by the authors, specifically the lack of evidence on rare and long-term effects and the potential for small studies to overestimate benefits of aspirin treatment. The authors accurately summarised the findings of the included evidence, acknowledged its limitations, and identified important uncertainties.

The carefully considered conclusions of this review are likely to be reliable.

Implications of the review for practice and research

The authors did not state any implications for practice.

Research: The authors stated that further research was needed to: determine how preeclampsia arising from different risk factors develops and responds to aspirin; allow better risk stratification; and establish more robust findings for African American women.

Funding

Agency for Healthcare Research and Quality, USA.

Bibliographic details

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 Annals of Internal Medicine 2014; 160(10): 695-703. [PubMed: 24711050]

Original Paper URL

http://annals.org/article.aspx?articleid=1859300

Other publications of related interest

Henderson JT, Whitlock EP, O’Conner E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for the prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Rockville, MD, USA: Agency for Healthcare Research and Quality. Evidence Synthesis; 112. 2014

Indexing Status

Subject indexing assigned by CRD

MeSH

Aspirin; Humans; Pre-Eclampsia; Pregnancy; Female; Administration, Oral; Platelet Aggregation Inhibitors

AccessionNumber

12014024712

Database entry date

08/05/2014

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.