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.
Medline, Embase, Google Scholar, Cochrane and Clinicaltrial.gov 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
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.