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

Stéphanie Roberge; Yves Giguère; Pia Villa; Kypros Nicolaides; Merja Vainio; Jean-Claude Forest; Peter von Dadelzen; Daniel Vaiman; Sylvie Tapp; Emmanuel Bujold

doi:10.1055/s-0032-1310527

American Journal of Perinatology, Table of Contents

Am J Perinatol 2012; 29(07): 551-556
DOI: 10.1055/s-0032-1310527

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Authors

Stéphanie Roberge

¹Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec, Canada
Yves Giguère

²Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Quebec, Canada
Pia Villa

³Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Kypros Nicolaides

⁴Harris Birthright Research Centre of Fetal Medicine, King's College Hospital, London, United Kingdom
Merja Vainio

⁵Kanta-Häme Central Hospital, Hämeenlinna, Finland
Jean-Claude Forest

²Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Quebec, Canada
Peter von Dadelzen

⁶Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
Daniel Vaiman

⁷Genomics and Epigenetics of Human Reproduction, Institut Cochin, Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes, Paris, France
Sylvie Tapp

¹Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec, Canada
Emmanuel Bujold

⁸Department of Obstetrics and Gynecology, Faculty of Medecine, Université Laval, Quebec, Canada

Abstract

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.

Keywords

pregnancy - preeclampsia - aspirin - systematic review - meta-analysis

Full Text

References

References
1 World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet Gynecol 1988; 158: 80-83
2 Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33: 130-137
3 Magee LA, Helewa M, Moutquin JM, von Dadelszen P. ; Hypertension Guideline Committee; Strategic Training Initiative in Research in the Reproductive Health Sciences (STIRRHS) Scholars. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. J Obstet Gynaecol Can 2008; 30 (3, Suppl) S1-S48
4 Moldenhauer JS, Stanek J, Warshak C, Khoury J, Sibai B. The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. Am J Obstet Gynecol 2003; 189: 1173-1177
5 Odegård RA, Vatten LJ, Nilsen ST, Salvesen KA, Austgulen R. Preeclampsia and fetal growth. Obstet Gynecol 2000; 96: 950-955
6 von Dadelszen P, Payne B, Li J , et al; PIERS Study Group. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet 2011; 377: 219-227
7 MacKay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 2001; 97: 533-538
8 Bujold E, Roberge S, Lacasse Y , et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010; 116 (2 Pt 1) 402-414
9 Schiff E, Peleg E, Goldenberg M , 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. N Engl J Med 1989; 321: 351-356
10 Haapsamo M, Martikainen H, Räsänen J. Low-dose aspirin reduces uteroplacental vascular impedance in early and mid gestation in IVF and ICSI patients: a randomized, placebo-controlled double-blind study. Ultrasound Obstet Gynecol 2008; 32: 687-693
11 Vainio M, Kujansuu E, Iso-Mustajärvi M, Mäenpää J. Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. BJOG 2002; 109: 161-167
12 Askie LM, Duley L, Henderson-Smart DJ, Stewart LA ; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007; 369: 1791-1798
13 Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007; (2) CD004659
14 Coomarasamy A, Honest H, Papaioannou S, Gee H, Khan KS. Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review. Obstet Gynecol 2003; 101: 1319-1332
15 Moher D, Liberati A, Tetzlaff J, Altman DG ; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097
16 Higgins JPT, Green S (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available at: www.cochrane-handbook.org
17 ACOG Committee on Obstetric Practice; American College of Obstetricians and Gynecologists. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Int J Gynaecol Obstet 2002; 77: 67-75
18 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
19 Chevalier P, van Driel M, Vermeire E. Hétérogénité dans les synthèses méthodiques et méta-analyses. Minerva 2007; 6: 160
20 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
21 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
22 August P, Helseth G, Edersheim TG, Hutson JM, Druzin M. Sustained relase, low-dose aspirin ameliorates but does not prevent preeclampsia (PE) in a high risk population. Proceedings of 9th International Congress, International Society for the Study of Hypertension. Sydney, Australia: Hypertension in Pregnancy; 1994: 72 .
23 Villa P, Taipale P, Räikkönen K , et al. PREDO trial—acetylsalicylic acid in preventing pre-eclampsia in high-risk women. 17th ISSHP World Congress at Melbourne, Australia in October 2010, Pregnancy Hypertension: 2010: S1-S41
24 Ebrashy A, Ibrahim M, Marzook A, Yousef D. Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14–16 weeks pregnancy: randomized controlled clinical trial. Croat Med J 2005; 46: 826-831
25 Azar R, Turpin D. Effect of Antiplatelet Therapy in Women at High Risk for Pregnancy-Induced Hypertension. Perugia, Italy: Proceedings of 7th World Congress of Hypertension in Pregnancy; 1990: 257
26 Bakhti A, Vaiman D. Prevention of gravidic endothelial hypertension by aspirin treatment administered from the 8th week of gestation. Hypertens Res 2011; 34: 1116-1120
27 Beaufils M, Uzan S, Donsimoni R, Colau JC. Prevention of pre-eclampsia by early antiplatelet therapy. Lancet 1985; 1: 840-842
28 Benigni A, Gregorini G, Frusca T , et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med 1989; 321: 357-362
29 Hermida RC, Ayala DE, Iglesias M , et al. Time-dependent effects of low-dose aspirin administration on blood pressure in pregnant women. Hypertension 1997; 30 (3 Pt 2) 589-595
30 Mesdaghinia E, Talari H, Zolfagharpour A, Abedzadeh M, Rezapourian P ; Focused Conference Group. P15—Endothelium in health and disease aspirin may prevent preeclampsia and its complications in women with abnormal uterine artery Doppler ultrasound. Basic Clin Pharmacol Toxicol 2010; 107: 453
31 Michael C, Walters B. Low-dose aspirin in the prevention of pre-eclampsia: current evaluation. In: Teoh ESR, Macnaughton MC, eds. Maternal physiology and pathology. The current status of gynaecology and obstetrics serie. Carnforth, England: Parthenon; 1992: 183-189
32 Tulppala M, Marttunen M, Söderstrom-Anttila V , 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. Hum Reprod 1997; 12: 1567-1572
33 Yu CK, Khouri O, Onwudiwe N, Spiliopoulos Y, Nicolaides KH ; Fetal Medicine Foundation Second-Trimester Screening Group. Prediction of pre-eclampsia by uterine artery Doppler imaging: relationship to gestational age at delivery and small-for-gestational age. Ultrasound Obstet Gynecol 2008; 31: 310-313
34 Pijnenborg R, Anthony J, Davey DA , et al. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol 1991; 98: 648-655
35 Menzies J, Magee LA, Macnab YC , et al. Current CHS and NHBPEP criteria for severe preeclampsia do not uniformly predict adverse maternal or perinatal outcomes. Hypertens Pregnancy 2007; 26: 447-462
36 CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet 1994; 343: 619-629
37 Caritis S, Sibai B, Hauth J , 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: 701-705
38 ECPPA. ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA (Estudo Colaborativo para Prevenção da Pré-eclampsia com Aspirina) Collaborative Group. Br J Obstet Gynaecol 1996; 103: 39-47
39 Golding J ; The Jamaica Low Dose Aspirin Study Group. A randomised trial of low dose aspirin for primiparae in pregnancy. Br J Obstet Gynaecol 1998; 105: 293-299
40 Rotchell YE, Cruickshank JK, Gay MP , et al. Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications. Br J Obstet Gynaecol 1998; 105: 286-292
41 Hauth JC, Goldenberg RL, Parker Jr CR , et al. Low-dose aspirin therapy to prevent preeclampsia. Am J Obstet Gynecol 1993; 168: 1083-1091 ; discussion 1091–1093
42 Bujold E, Tapp S, Audibert F , et al. Prevention of adverse pregnancy outcomes with low-dose ASA in early pregnancy: new perspectives for future randomized trials. J Obstet Gynaecol Can 2011; 33: 480-483
43 Poon LC, Stratieva V, Piras S, Piri S, Nicolaides KH. Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP-A at 11–13 weeks. Prenat Diagn 2010; 30: 216-223
44 Giguère Y, Charland M, Bujold E , et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin Chem 2010; 56: 361-375
45 Akolekar R, Syngelaki A, Sarquis R, Zvanca M, Nicolaides KH. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11–13 weeks. Prenat Diagn 2011; 31: 66-74
46 Dumont A, Flahault A, Beaufils M, Verdy E, Uzan S. Effect of aspirin in pregnant women is dependent on increase in bleeding time. Am J Obstet Gynecol 1999; 180 (1 Pt 1) 135-140
47 Rey E, Rivard GE. Is testing for aspirin response worthwhile in high-risk pregnancy?. Eur J Obstet Gynecol Reprod Biol 2011; 157: 38-42
48 Wójtowicz A, Undas A, Huras H , et al. Aspirin resistance may be associated with adverse pregnancy outcomes. Neuroendocrinol Lett 2011; 32: 334-339