Early Administration of Low-Dose Aspirin for the Prevention of Severe and Mild Preeclampsia: A Systematic Review and Meta-Analysis

OBJECTIVE To determine whether early administration of aspirin prevents severe and mild preeclampsia. STUDY DESIGN A systematic review and meta-analysis of randomized controlled trials were performed. Studies in which women were randomized at or before 16 weeks' gestation to low-dose aspirin versus placebo or no treatment were included. The outcomes of interest were severe preeclampsia and mild preeclampsia. Pooled relative risks with their 95% confidence intervals (CIs) were calculated. RESULTS Among 7941 citations retrieved, 352 were completely reviewed and four studies (392 women) fulfilled the inclusion criteria and were analyzed. When compared with controls, aspirin started at ≤16 weeks was associated with a significant reduction in severe (relative risk: 0.22, 95% CI: 0.08 to 0.57) but not mild (relative risk: 0.81, 95% CI: 0.33 to 1.96) preeclampsia. CONCLUSION Low-dose aspirin initiated at or before 16 weeks reduces the risk of severe preeclampsia, but not mild preeclampsia.

[1]  A. Seidler,et al.  Antiplatelet agents for preventing pre-eclampsia and its complications. , 2007, The Cochrane database of systematic reviews.

[2]  E. Ruppin,et al.  The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. , 1990, The New England journal of medicine.

[3]  J. Hutcheon,et al.  Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model , 2011, The Lancet.

[4]  R. Collins,et al.  Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre‐eclampsia and its complications , 1998, British journal of obstetrics and gynaecology.

[5]  G. Remuzzi,et al.  Effect of low‐dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy‐induced hypertension , 1990, The New England journal of medicine.

[6]  E. Kujansuu,et al.  Low dose acetylsalicylic acid in prevention of pregnancy‐induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches , 2002, BJOG : an international journal of obstetrics and gynaecology.

[7]  K. Nicolaides,et al.  Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP‐A at 11–13 weeks , 2010, Prenatal diagnosis.

[8]  H. Honest,et al.  Aspirin for Prevention of Preeclampsia in Women With Historical Risk Factors: A Systematic Review , 2003, Obstetrics and gynecology.

[9]  François Audibert,et al.  Prevention of Preeclampsia and Intrauterine Growth Restriction With Aspirin Started in Early Pregnancy: A Meta-Analysis , 2010, Obstetrics and gynecology.

[10]  Argyro Syngelaki,et al.  Prediction of early, intermediate and late pre‐eclampsia from maternal factors, biophysical and biochemical markers at 11–13 weeks , 2011, Prenatal diagnosis.

[11]  ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. , 2002, Obstetrics and gynecology.

[12]  Lelia Duley,et al.  The global impact of pre-eclampsia and eclampsia. , 2009, Seminars in perinatology.

[13]  H. Martikainen,et al.  Low‐dose aspirin reduces uteroplacental vascular impedance in early and mid gestation in IVF and ICSI patients: a randomized, placebo‐controlled double‐blind study , 2008, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[14]  Y. MacNab,et al.  Current CHS and NHBPEP Criteria for Severe Preeclampsia Do Not Uniformly Predict Adverse Maternal or Perinatal Outcomes , 2007, Hypertension in pregnancy.

[15]  A. Flahault,et al.  Effect of aspirin in pregnant women is dependent on increase in bleeding time. , 1999, American journal of obstetrics and gynecology.

[16]  Jean Golding,et al.  Geographic variation in incidence of hypertension in pregnancy , 1988 .

[17]  V. Söderström-Anttila,et al.  Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. , 1997, Human reproduction.

[18]  C. Berg,et al.  Pregnancy‐Related Mortality From Preeclampsia and Eclampsia , 2001, Obstetrics and gynecology.

[19]  F. Légaré,et al.  Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. , 2010, Clinical chemistry.

[20]  W. Fraser,et al.  Prevention of adverse pregnancy outcomes with low-dose ASA in early pregnancy: new perspectives for future randomized trials. , 2011, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[21]  G. Rivard,et al.  Is testing for aspirin response worthwhile in high-risk pregnancy? , 2011, European journal of obstetrics, gynecology, and reproductive biology.

[22]  Jeffrey R. Wilson,et al.  CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women , 1994, The Lancet.

[23]  Bethany J Figg,et al.  National Institute of Child Health and Human Development , 2013 .

[24]  J. Dungan.  Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data , 2008 .

[25]  R. Pijnenborg,et al.  Placental bed spiral arteries in the hypertensive disorders of pregnancy , 1991, British journal of obstetrics and gynaecology.

[26]  J. Golding,et al.  A randomised trial of low dose aspirin for primiparae in pregnancy , 1998, British journal of obstetrics and gynaecology.

[27]  G. Cutter,et al.  Low-dose aspirin therapy to prevent preeclampsia. , 1993, American journal of obstetrics and gynecology.

[28]  Daniel Vaiman,et al.  Prevention of gravidic endothelial hypertension by aspirin treatment administered from the 8th week of gestation , 2011, Hypertension Research.

[29]  E. Ruppin,et al.  The use of aspirin to prevent pregnancy‐induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies , 1989, The New England journal of medicine.

[30]  R. Collins,et al.  ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women , 1996, British journal of obstetrics and gynaecology.

[31]  A. Ebrashy,et al.  Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14-16 weeks pregnancy: randomized controlled clinical trial. , 2005, Croatian medical journal.

[32]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[33]  J. Higgins.  Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[34]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[35]  R. Hermida,et al.  Time-dependent effects of low-dose aspirin administration on blood pressure in pregnant women. , 1997, Hypertension.

[36]  S. Uzan,et al.  PREVENTION OF PRE-ECLAMPSIA BY EARLY ANTIPLATELET THERAPY , 1985, The Lancet.

[37]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[38]  B. Sibai,et al.  The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. , 2003, American journal of obstetrics and gynecology.

[39]  L. Vatten,et al.  Preeclampsia and Fetal Growth , 2000, Obstetrics and gynecology.

[40]  A. Wójtowicz,et al.  Aspirin resistance may be associated with adverse pregnancy outcomes. , 2011, Neuro endocrinology letters.