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

Published:November 16, 2022DOI:



      To investigate the potential role of Aspirin in reducing the risk of pre-eclampsia (PE), as well as adverse maternal and perinatal outcomes in twin pregnancies.

      Data sources

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

      Study eligibility criteria

      The search and selection criteria were restricted to English language.

      Study appraisal and synthesis methods

      The primary outcome was the incidence of PE. The secondary outcomes included gestational hypertension, fetal growth restriction (FGR), preterm birth (PTB), either spontaneous or iatrogenic, prior to 34 weeks’ gestation, gestational age (GA) at birth, neonatal birthweight and adverse events secondary to Aspirin administration, including ante and post-partum hemorrhage. Sub-group analyses according to chorionicity (dichorionic vs monochorionic), Aspirin dose, considering only studies with daily Aspirin dose ≥100mg/day, and gestational age at Aspirin administration (< vs≥16 weeks of gestation) were also performed. Head-to-head meta-analyses reporting results as summary odds ratios (OR) and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trial was independently performed by two researchers based on the Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The conclusion of the meta-analysis on the primary outcome was assessed using GRADE.


      Nine studies (2273 twin pregnancies) were included. When considering all studies, the risk of PE was lower in twin pregnancies treated compared to those not treated with Aspirin (OR 0.64; 95% CI 0.48-0.85, p=0.003), while there was no significant difference in the risk of gestational hypertension (p=0.987), FGR (p=0.9) or adverse maternal and perinatal events (p=0.9) compared to those not treated. There were no significant differences in the GA at birth (p=0.2) and neonatal birthweight (p=0.06) between women receiving compared to those not receiving Aspirin. When considering only studies with Aspirin dose >100 mg/day, the risk of PE (OR 0.45, 95% CI 0.23-0.86, p=0.02) was significantly lower in pregnancies taking comparing to those not taking Aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (p=0.20), FGR (p= 0.1), GA at birth (p=0.06) and neonatal weight (p=0.05) between the two groups. Likewise, there was no significant difference in the risk of PE when considering only studies with Aspirin dose >80 mg/day (p= 0.611). The association between Aspirin administration PE persisted when considering aspirin dose >100 mg/day or when the drug was started before 16 weeks of gestation. The overall quality of evidence using GRADE assessment was low.


      Administration of Aspirin in women with twin pregnancies reduces the risk of PE. The findings from this study highlight the need for randomized controlled trial elucidating the actual role of Aspirin in affecting maternal and perinatal outcome in twin pregnancies.


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