Context
Low-dose aspirin is used for pre-eclampsia prophylaxis during pregnancy, but a study
that comprehensively investigates both maternal and perinatal outcomes from aspirin
administration utilizing stratification methods is lacking. The aim of this study
is to comprehensively investigate the maternal and neonatal outcomes related to aspirin
prophylaxis during pregnancy in relation to dose and therapy initiation by utilizing
a stratification method.
Evidence acquisition
Placebo-controlled randomized trials investigating the effect of low-dose aspirin
on maternal or perinatal outcomes with sufficient raw data and published in English
from inception to August 2020 were searched for from PubMed, Embase, Cochrane Library,
and Google Scholar in accordance with PRISMA guidelines. Review articles, editorials,
case reports, conference abstracts, and nonplacebo-controlled studies were excluded.
Evidence synthesis
A total of 35 placebo-controlled randomized trials with 46,568 pregnant women were
included in this meta-analysis. Aspirin prophylaxis substantially lowered the risk
of pre-eclampsia, preterm birth, perinatal mortality, and intrauterine growth retardation
without elevated bleeding risks. Low-dose aspirin considerably enhanced neonatal birth
weight but did not decrease the risk of gestational hypertension. The subgroup analysis
revealed substantially reduced pre-eclampsia risk and enhanced birth weight and gestational
age at delivery in women who initiated aspirin before 20 weeks of gestation (RR=0.76,
95% CI=0.64, 0.90, p=0.001). However, the effect of aspirin dose on pregnancy outcomes was insignificant
and requires further evaluation.
Conclusions
Initiation of low-dose aspirin administration before 20 weeks of gestation considerably
decreases the incidence of pre-eclampsia and related neonatal outcomes without increasing
bleeding risk.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Preventive MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
REFERENCES
- Pre-eclampsia.Lancet. 2010; 376: 631-644https://doi.org/10.1016/S0140-6736(10)60279-6
- Epidemiology of preeclampsia: impact of obesity.Nutr Rev. 2013; 71: S18-S25https://doi.org/10.1111/nure.12055
- The global impact of pre-eclampsia and eclampsia.Semin Perinatol. 2009; 33: 130-137https://doi.org/10.1053/j.semperi.2009.02.010
- Peripartum intensive care.J Matern Fetal Neonatal Med. 2010; 23: 1136-1138https://doi.org/10.3109/14767058.2010.490890
- Prevention of premature birth.N Engl J Med. 1998; 339: 313-320https://doi.org/10.1056/NEJM199807303390506
- Preeclampsia prevention: lessons from the low-dose aspirin therapy trials.Am J Obstet Gynecol. 2000; 183: 523-528https://doi.org/10.1067/mob.2000.106757
- The developmental origins of chronic adult disease.Acta Paediatr Suppl. 2004; 93: 26-33https://doi.org/10.1111/j.1651-2227.2004.tb00236.x
- Impact of low-dose aspirin on adverse perinatal outcome: meta-analysis and meta-regression.Ultrasound Obstet Gynecol. 2020; 55: 157-169https://doi.org/10.1002/uog.20859
- Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis.Obstet Gynecol. 2010; 116 (Pt 1): 402-414https://doi.org/10.1097/AOG.0b013e3181e9322a
- Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis.Am J Obstet Gynecol. 2018; 218: 287-293.e1https://doi.org/10.1016/j.ajog.2017.11.561
- Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis.Ultrasound Obstet Gynecol. 2013; 41: 491-499https://doi.org/10.1002/uog.12421
- Bleeding risk with long-term low-dose aspirin: a systematic review of observational studies.PLoS One. 2016; 11e0160046https://doi.org/10.1371/journal.pone.0160046
- CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group.Lancet. 1994; 343: 619-629https://doi.org/10.1016/S0140-6736(94)92633-6
- Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.Ann Intern Med. 2009; 151 (W64): 264-269https://doi.org/10.7326/0003-4819-151-4-200908180-00135
- Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation [published correction appears in BMJ. 2016;354:i4086].BMJ. 2015; 350: g7647https://doi.org/10.1136/bmj.g7647
- Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial [published correction appears in Lancet. 2020;395(10228):e53].Lancet. 2020; 395: 285-293https://doi.org/10.1016/S0140-6736(19)32973-3
- Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.N Engl J Med. 2017; 377: 613-622https://doi.org/10.1056/NEJMoa1704559
- Aspirin (100 mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional aspirine Mère–Enfant study (part 1).BJOG. 2003; 110: 475-484https://doi.org/10.1046/j.1471-0528.2003.02096.x
- Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial.Aust N Z J Obstet Gyanecol. 1995; 35: 370-374https://doi.org/10.1111/j.1479-828x.1995.tb02144.x
- Low-dose aspirin in primigravidae with positive roll-over test.Gynecol Obstet Invest. 1992; 34: 146-150https://doi.org/10.1159/000292748
- 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: 286-292https://doi.org/10.1111/j.1471-0528.1998.tb10088.x
- 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: 39-47https://doi.org/10.1111/j.1471-0528.1996.tb09513.x
- Effects of low-dose aspirin on the prevention of preeclampsia and pregnancy outcomes: a randomized controlled trial from Shanghai, China.Eur J Obstet Gynecol Reprod Biol. 2020; 248: 156-163https://doi.org/10.1016/j.ejogrb.2020.03.038
- A prospective randomized placebo-controlled trial of low-dose aspirin for prevention of intra-uterine growth retardation.Chin Med J (Engl). 1996; 109: 238-242https://journals.lww.com/cmj/pages/default.aspxDate accessed: August 12, 2020
- Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials.BJOG. 2013; 120: 64-74https://doi.org/10.1111/j.1471-0528.2012.03493.x
- 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: 1567-1572https://doi.org/10.1093/humrep/12.7.1567
- Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches.BJOG. 2002; 109: 161-167https://doi.org/10.1111/j.1471-0528.2002.01046.x
- Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo-controlled, double-blind trial.Ultrasound Obstet Gynecol. 2000; 15: 19-27https://doi.org/10.1046/j.1469-0705.2000.00009.x
- Aspirin and preeclampsia prevention in patients with abnormal uterine artery blood flow.Iran Red Crescent Med J. 2014; 16: e17175https://doi.org/10.5812/ircmj.17175
- Prevention of pregnancy-induced hypertension in twins by early administration of low-dose aspirin: a preliminary report.Am J Repord Immunol. 1994; 31: 19-24https://doi.org/10.1111/j.1600-0897.1994.tb00842.x
- Low-dose aspirin does not influence the clinical course of women with mild pregnancy-induced hypertension.Obstet Gynecol. 1990; 76 (Pt 1): 742-744https://doi.org/10.1097/00006250-199011000-00002
- 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: 351-356https://doi.org/10.1056/NEJM198908103210603
- A randomised trial of low dose aspirin for primiparae in pregnancy. The Jamaica Low Dose Aspirin Study Group.Br J Obstet Gynaecol. 1998; 105: 293-299https://doi.org/10.1111/j.1471-0528.1998.tb10089.x
- Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae.Lancet. 1986; 1: 1-3https://doi.org/10.1016/s0140-6736(86)91891-x
- Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial.Br J Obstet Gynaecol. 1999; 106: 647-651https://doi.org/10.1111/j.1471-0528.1999.tb08362.x
- Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial.Am J Obstet Gynecol. 2000; 183: 1008-1012https://doi.org/10.1067/mob.2000.106754
- Chronotherapy with low-dose aspirin for prevention of complications in pregnancy.Chronobiol Int. 2013; 30: 260-279https://doi.org/10.3109/07420528.2012.717455
- Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.Ultrasound Obstet Gynecol. 2017; 49: 435-441https://doi.org/10.1002/uog.17351
- Time-dependent effects of low-dose aspirin administration on blood pressure in pregnant women.Hypertension. 1997; 30: 589-595https://doi.org/10.1161/01.hyp.30.3.589
- Randomized controlled trial using low-dose aspirin in the prevention of pre-eclampsia in women with abnormal uterine artery Doppler at 23 weeks’ gestation.Ultrasound Obstet Gynecol. 2003; 22: 233-239https://doi.org/10.1002/uog.218
- A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow.Obstet Gynecol. 1996; 87: 74-78https://doi.org/10.1016/0029-7844(95)00340-1
- Doppler ultrasound and aspirin in recognition and prevention of pregnancy-induced hypertension.Lancet. 1990; 335: 1552-1555https://doi.org/10.1016/0140-6736(90)91377-m
- The angiotensin sensitivity test and low-dose aspirin are ineffective methods to predict and prevent hypertensive disorders in nulliparous pregnancy.Am J Obstet Gynecol. 1995; 173: 865-872https://doi.org/10.1016/0002-9378(95)90356-9
- Prediction of pre-eclampsia by abnormal uterine Doppler ultrasound and modification by aspirin.Br J Obstet Gynaecol. 1996; 103: 625-629https://doi.org/10.1111/j.1471-0528.1996.tb09829.x
- Low-dose aspirin in the prevention of hypertensive disorders of pregnancy in relatively low-risk nulliparous women.Hypertens Preg. 1995; 14: 49-55https://doi.org/10.3109/10641959509058050
- Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.N Engl J Med. 1998; 338: 701-705https://doi.org/10.1056/NEJM199803123381101
- Early prediction and aspirin for prevention of pre-eclampsia (EPAPP) study: a randomized controlled trial.Ultrasound Obstet Gynecol. 2015; 46: 414-418https://doi.org/10.1002/uog.14889
- Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.N Engl J Med. 1993; 329: 1213-1218https://doi.org/10.1056/NEJM199310213291701
- A randomized controlled trial of low-dose aspirin in women at risk from pre-eclampsia.Int J Gynecol Obstet. 1998; 60: 129-135https://doi.org/10.1016/S0020-7292(97)00257-9
- ACOG Committee opinion no. 743: low-dose aspirin use during pregnancy.Am J Obstset Gynecol. 2018; 132: e44-e52https://doi.org/10.1097/aog.0000000000002708
Use of aspirin for primary prevention of heart attack and stroke. Food and Drug Administration; United States. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/use-aspirin-primary-prevention-heart-attack-and-stroke. Updated December 30, 2016. Accessed September 12, 2020.
- Risk factors and poor prognostic factors of preeclampsia in Ibn Rochd University Hospital of Casablanca: about 401 preeclamptic cases.Pan Afr Med J. 2018; 31: 225https://doi.org/10.11604/pamj.2018.31.225.14401
- The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.Am J Obstet Gynecol. 2017; 216: 110-120.e6https://doi.org/10.1016/j.ajog.2016.09.076
- Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222.Obstet Gynecol. 2020; 135: e237-e260https://doi.org/10.1097/AOG.0000000000003891
- Hypertension in Pregnancy: diagnosis and management: NICE guideline [NG133].National Institute for Health and Care Excellence, London, United Kingdom2019 (Published June 25,Accessed September 20, 2020)
Article Info
Publication History
Published online: March 30, 2021
Identification
Copyright
© 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
