Low-Dose Aspirin in Early Gestation for Prevention of Preeclampsia and Small-for-Gestational-Age Neonates: Meta-analysis of Large Randomized Trials

 

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Abstract

Objectives Meta-analyses of small to moderate size randomized controlled trials (RCTs) suggested that aspirin started before 17 weeks' gestation reduces the risk of preeclampsia and small-for-gestational-age (SGA) neonates. We evaluated data from large randomized trials originally excluded from meta-analyses.

Methods We performed meta-analyses of RCTs including more than 350 participants that compared aspirin to placebo during pregnancy. Corresponding authors were contacted to obtain data according to gestational age. Outcomes included preeclampsia, severe preeclampsia, and SGA. Relative risks (RRs) with their 95% confidence intervals (CIs) were calculated.

Results Data for women recruited before 17 weeks' gestation were obtained for three (50%) of the six eligible trials for a total of 11,949 participants including 3,293 recruited before 17 weeks' gestation with available data. We observed no impact of low-dose aspirin (60 mg) started before 17 weeks' gestation on the risk of preeclampsia (RR: 0.93; 95% CI: 0.75–1.15), severe preeclampsia (RR: 0.96; 95% CI: 0.71–1.28), or SGA (RR: 0.84; 95% CI: 0.56–1.26) and it was not statistically different than when started at or after 17 weeks' gestation.

Conclusion Data from large randomized trials do not support greater benefits of low-dose aspirin (at 60 mg daily) when started before 17 weeks' gestation for the prevention of preeclampsia or SGA.

• References

• 1 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
  CrossrefPubMedGoogle Scholar
• 2 Roberge S, Nicolaides KH, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol 2013; 41 (5) 491-499
  CrossrefPubMedGoogle Scholar
• 3 Bujold E, Morency AM, Roberge S, Lacasse Y, Forest JC, Giguère Y. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J Obstet Gynaecol Can 2009; 31 (9) 818-826
  PubMedGoogle Scholar
• 4 Roberge S, Giguère Y, Villa P , et al. Early administration of low-dose aspirin for the prevention of severe and mild preeclampsia: a systematic review and meta-analysis. Am J Perinatol 2012; 29 (7) 551-556
  Article in Thieme ConnectPubMedGoogle Scholar
• 5 Roberge S, Villa P, Nicolaides K , et al. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther 2012; 31 (3) 141-146
  CrossrefPubMedGoogle Scholar
• 6 Dickersin K. The existence of publication bias and risk factors for its occurrence. JAMA 1990; 263 (10) 1385-1389
  CrossrefPubMedGoogle Scholar
• 7 Meher S, Alfirevic Z. Aspirin for pre-eclampsia: beware of subgroup meta-analysis. Ultrasound Obstet Gynecol 2013; 41 (5) 479-485
  CrossrefPubMedGoogle Scholar
• 8 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414) 557-560
  CrossrefPubMedGoogle Scholar
• 9 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 (8898) 619-629
  CrossrefPubMedGoogle Scholar
• 10 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 (3) 293-299
  CrossrefPubMedGoogle Scholar
• 11 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 (11) 701-705
  CrossrefPubMedGoogle Scholar
• 12 Sibai BM, Caritis SN, Thom E , et al; The 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) 1213-1218
  CrossrefPubMedGoogle Scholar
• 13 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 (3) 286-292
  CrossrefPubMedGoogle Scholar
• 14 Subtil D, Goeusse P, Puech F , et al; Essai Régional Aspirine Mère-Enfant (ERASME) Collaborative Group. Aspirin (100 mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 1). BJOG 2003; 110 (5) 475-484
  PubMedGoogle Scholar
• 15 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 (9575) 1791-1798
  CrossrefPubMedGoogle Scholar
• 16 Rey E, Rivard GE. Is testing for aspirin response worthwhile in high-risk pregnancy?. Eur J Obstet Gynecol Reprod Biol 2011; 157 (1) 38-42
  CrossrefPubMedGoogle Scholar
• 17 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
  CrossrefPubMedGoogle Scholar
• 18 Caron N, Rivard GE, Michon N , et al. Low-dose ASA response using the PFA-100 in women with high-risk pregnancy. J Obstet Gynaecol Can 2009; 31 (11) 1022-1027
  PubMedGoogle Scholar
• 19 Wójtowicz A, Undas A, Huras H , et al. Aspirin resistance may be associated with adverse pregnancy outcomes. Neuroendocrinol Lett 2011; 32 (3) 334-339
  PubMedGoogle Scholar