Advertisement

Aspirin for prevention of preeclampsia and adverse perinatal outcome in twin pregnancies: a systematic review and meta-analysis

Published:November 16, 2022DOI:https://doi.org/10.1016/j.ajogmf.2022.100803

      OBJECTIVE

      This study aimed to investigate the potential role of aspirin in reducing the risk of preeclampsia and adverse maternal and perinatal outcomes in twin pregnancies.

      DATA SOURCES

      Medline, Embase, Google Scholar, Cochrane, and ClinicalTrial.gov databases were searched.

      STUDY ELIGIBILITY CRITERIA

      The search and selection criteria were restricted to the English language.

      METHODS

      The primary outcome was the incidence of preeclampsia. The secondary outcomes included gestational hypertension; fetal growth restriction; preterm birth, either spontaneous or iatrogenic, before 34 weeks of gestation; gestational age at birth; neonatal birthweight; and adverse events secondary to the administration of aspirin, including antepartum and postpartum hemorrhage. In addition, subgroup analyses according to chorionicity (dichorionic vs monochorionic), aspirin dose, and gestational age at administration of aspirin (<16 vs ≥16 weeks of gestation) and considering only studies with a daily aspirin dose of ≥100 mg/d were performed. Head-to-head meta-analyses reporting results as summary odds ratios and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trials was independently performed by 2 researchers based on the risk of bias that was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The conclusion of the meta-analysis on the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation.

      RESULTS

      Overall, 9 studies (2273 twin pregnancies) were included. When considering all studies, the risk of preeclampsia was lower in twin pregnancies treated with aspirin than in those not treated with aspirin (odds ratio, 0.64; 95% confidence interval, 0.48–0.85; P=.003), although there was no significant difference in the risk of gestational hypertension (P=.987), fetal growth restriction (P=.9), or adverse maternal and perinatal events (P=.9) in twin pregnancies treated with aspirin compared with those not treated with aspirin. There was no significant difference in the gestational age at birth (P=.2) and neonatal birthweight (P=.06) between women receiving aspirin and those not receiving aspirin. When considering only studies with an aspirin dose of >100 mg/d, the risk of preeclampsia (odds ratio, 0.45; 95% confidence interval, 0.23–0.86; P=.02) was significantly lower in pregnancies receiving aspirin than in those not receiving aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (P=.20), fetal growth restriction (P=.1), gestational age at birth (P=.06), and neonatal weight (P=.05) between the 2 groups. Furthermore, there was no significant difference in the risk of preeclampsia when considering only studies with an aspirin dose of >80 mg/d (P=.611). The association between the administration of aspirin and preeclampsia persisted when considering an aspirin dose of >100 mg/day or when the medication was started before 16 weeks of gestation. The overall quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation assessment was low.

      CONCLUSION

      The administration of aspirin in women with twin pregnancies reduced the risk of preeclampsia. The findings from this study highlighted the need for randomized controlled trials elucidating the actual role of aspirin in affecting maternal and perinatal outcomes in twin pregnancies.

      Key words

      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 access
      One-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 Obstetrics & Gynecology MFM
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dall'Asta A
        • D'Antonio F
        • Saccone G
        • et al.
        Cardiovascular events following pregnancy complicated by pre-eclampsia with emphasis on comparison between early- and late-onset forms: systematic review and meta-analysis.
        Ultrasound Obstet Gynecol. 2021; 57: 698-709
        • Audette MC
        • Kingdom JC.
        Screening for fetal growth restriction and placental insufficiency.
        Semin Fetal Neonatal Med. 2018; 23: 119-125
        • Stepan H
        • Hund M
        • Andraczek T.
        Combining biomarkers to predict pregnancy complications and redefine preeclampsia: the angiogenic-placental syndrome.
        Hypertension. 2020; 75: 918-926
        • Scott G
        • Gillon TE
        • Pels A
        • von Dadelszen P
        • Magee LA.
        Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension.
        Am J Obstet Gynecol. 2022; 226: S1222-S1236
        • Choi YJ
        • Shin S.
        Aspirin prophylaxis during pregnancy: a systematic review and meta-analysis.
        Am J Prev Med. 2021; 61: e31-e45
        • Hoffman MK
        • Goudar SS
        • Kodkany BS
        • et al.
        Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.
        Lancet. 2020; 395: 285-293
        • Bartsch E
        • Medcalf KE
        • Park AL
        • Ray JG
        • High Risk of Pre-eclampsia Identification Group
        Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies.
        BMJ. 2016; 353: i1753
        • Mehta LS
        • Warnes CA
        • Bradley E
        • et al.
        Cardiovascular considerations in caring for pregnant patients: a scientific statement from the American Heart Association.
        Circulation. 2020; 141: e884-e903
      1. Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222.
        Obstet Gynecol. 2020; 135: e237-e260
        • Brennecke SP
        • Brown MA
        • Crowther CA
        • et al.
        Aspirin and prevention of preeclampsia. Position statement of the use of low-dose aspirin in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy.
        Aust N Z J Obstet Gynaecol. 1995; 35: 38-41
        • Bates SM
        • Greer IA
        • Middeldorp S
        • Veenstra DL
        • Prabulos AM
        • Vandvik PO.
        VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2012; 141 (e691S–736S)
        • Poon LC
        • Shennan A
        • Hyett JA
        • et al.
        The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention.
        Int J Gynaecol Obstet. 2019; 145: 1-33
        • Preventive Services Task Force US
        • Davidson KW
        • Barry MJ
        • et al.
        Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force recommendation statement.
        JAMA. 2021; 326: 1186-1191
        • Lowe SA
        • Bowyer L
        • Lust K
        • et al.
        SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014.
        Aust N Z J Obstet Gynaecol. 2015; 55: e1-29
        • Webster K
        • Fishburn S
        • Maresh M
        • Findlay SC
        • Chappell LC
        • Committee Guideline
        Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance.
        BMJ. 2019; 366: l5119
        • Regitz-Zagrosek V
        • Roos-Hesselink JW
        • Bauersachs J
        • et al.
        2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy.
        Eur Heart J. 2018; 39: 3165-3241
        • Henderson LK
        • Craig JC
        • Willis NS
        • Tovey D
        • Webster AC.
        How to write a Cochrane systematic review.
        Nephrology (Carlton). 2010; 15: 617-624
      2. Centre for Reviews and Dissemination. Systematic reviews: CRD's guidance for undertaking reviews in health care. 2009. Available at: https://www.york.ac.uk/media/crd/Systematic_Reviews.pdf. Accessed December 3, 2016.

        • Welch V
        • Petticrew M
        • Petkovic J
        • et al.
        Extending the PRISMA statement to equity-focused systematic reviews (PRISMA-E 2012): explanation and elaboration.
        J Clin Epidemiol. 2016; 70: 68-89
        • Moher D
        • Liberati A
        • Tetzlaff J
        • Altman DG
        • PRISMA Group
        Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
        Ann Intern Med. 2009; 151: 264-269
        • Zorzela L
        • Loke YK
        • Ioannidis JP
        • et al.
        PRISMA harms checklist: improving harms reporting in systematic reviews.
        BMJ. 2016; 352: i157
        • Stroup DF
        • Berlin JA
        • Morton SC
        • et al.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
      3. Wells GA, Shea B, O'Connell D, et al. Newcastle-Ottawa Scale for assessing the quality of nonrandomised studies in meta- analyses. Ottawa Hospital Research Institute. 2011. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 2011.

        • Bradburn MJ
        • Deeks JJ
        • Berlin JA
        • Russell Localio A.
        Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events.
        Stat Med. 2007; 26: 53-77
      4. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration. 2011. Available at: www.cochrane-handbook.org. Accessed 2011.

        • Sterne JA
        • Sutton AJ
        • Ioannidis JP
        • et al.
        Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.
        BMJ. 2011; 343: d4002
        • Egger M
        • Davey Smith G
        • Schneider M
        • Minder C
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Carpentier C
        • Guerby P
        • Camiré B
        • Tapp S
        • Boutin A
        • Bujold E.
        Aspirin responsiveness at a dose of 80 mg and its impact on birth weight when used in twin pregnancies: the GAP Pilot Randomized Trial.
        Am J Perinatol. 2022; 39: 1396-1400
        • Ye Y
        • Wen L
        • Liu X
        • et al.
        Low-dose aspirin for primary prevention of adverse pregnancy outcomes in twin pregnancies: an observational cohort study based on propensity score matching.
        BMC Pregnancy Childbirth. 2021; 21: 786
        • Kalafat E
        • Shirazi A
        • Thilaganathan B
        • Khalil A.
        The role of aspirin in prevention of preeclampsia in twin pregnancies: does the dose matter?.
        Am J Obstet Gynecol. 2020; 223: 457-458
        • Euser AG
        • Metz TD
        • Allshouse AA
        • Heyborne KD.
        Low-dose aspirin for pre-eclampsia prevention in twins with elevated human chorionic gonadotropin.
        J Perinatol. 2016; 36: 601-605
        • Golding J.
        A randomised trial of low dose aspirin for primiparae in pregnancy. The Jamaica low dose aspirin study group.
        Br J Obstet Gynaecol. 1998; 105: 293-299
        • Caritis S
        • Sibai B
        • Hauth J
        • et al.
        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: 701-705
        • Caspi E
        • Raziel A
        • Sherman D
        • Arieli S
        • Bukovski I
        • Weinraub Z.
        Prevention of pregnancy-induced hypertension in twins by early administration of low-dose aspirin: a preliminary report.
        Am J Reprod Immunol. 1994; 31: 19-24
        • Sibai BM
        • Caritis SN
        • Thom E
        • et al.
        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: 1213-1218
        • Porreco RP
        • Hickok DE
        • Williams MA
        • Krenning C.
        Low-dose aspirin and hypertension in pregnancy.
        Lancet. 1993; 341: 312
        • Roberge S
        • Nicolaides K
        • Demers S
        • Hyett J
        • Chaillet N
        • Bujold E.
        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 (110–20.e6)
        • Cnossen JS
        • Morris RK
        • ter Riet G
        • et al.
        Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.
        CMAJ. 2008; 178: 701-711
        • Hiersch L
        • Ray JG
        • Barrett J
        • et al.
        Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study.
        CMAJ. 2021; 193: E1448-E1458
        • Hastie R
        • Tong S
        • Wikström AK
        • Sandström A
        • Hesselman S
        • Bergman L.
        Aspirin use during pregnancy and the risk of bleeding complications: a Swedish population-based cohort study.
        Am J Obstet Gynecol. 2021; 224 (95.e1–12)