Comparison of two aspirin doses for the prophylaxis of pre-eclampsia in twin pregnancy: a multicentre retrospective study with propensity score matching.

Background: Aspirin has proved its efficacy in reducing the rate of preeclampsia in singleton pregnancy, however, there is discrepancy about the efficient dosage that should be used. While some societies recommend daily 75-81mg, others recommend higher dosage (160mg). This discrepancy is due to the lack of randomized controlled studies that compare these two dosages. Moreover, there remains a considerable gap in our knowledge concerning the appropriate prophylactic aspirin dosage for twin pregnancies.

Objective: This study aimed to assess the efficacy of various aspirin prophylaxis dosages in the prevention of preeclampsia and hypertensive disorders of pregnancy (HDP) in twin pregnancies.

Study design: This was an international multicentre retrospective cohort study that was conducted in three European centers. We included all twin pregnancies with 2 live fetuses at 13 weeks of gestation (WG). We excluded fetal malformations, twin-twin transfusion syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion sequence, twin pregnancies at onset but continued as singletons (vanishing twin/arrest before 13 WG), and loss of follow-up. Patients were categorized into three groups: no aspirin, daily 80-100mg aspirin, and daily 160mg aspirin. Primary outcomes were the incidence of preeclampsia and HDP, whereas secondary outcomes were small-for-gestational age, postpartum hemorrhage>1000 mL, antenatal bleeding of obstetrical origin, thrombocytopenia, miscarriage, intrauterine fetal demise (IUFD), neonatal death, and gastritis. Propensity score matching and multivariate analyses were conducted to assess outcomes including pre-eclampsia, gestational hypertension, maternal complications, and gastritis. Propensity score matching was used to balance the three groups of study. Cox regression models were done for each outcome after matching to compare the three groups. A p-value<0.05 was considered statistically significant.

Results: A total of 1907 twin pregnancies were included: 1423 (74,62%) received no aspirin, 212 (11.12%) received 80-100 mg, and 272 (14.26%) received 160 mg. After using propensity score matching for maternal age, body mass index, race, parity, history of preeclampsia, chronic hypertension, diabetes mellitus, thrombophilia, spontaneous conception, and type of twin pregnancy, the three groups were adequately balanced (absolute standardized difference [ASD] <15%), except for age and thrombophilia (ASD 22.1% and 16.4% respectively). The administration of aspirin 160mg decreased the hazard ratio (HR) for preeclampsia to 0.63 and for HDP to 0.56, whereas the administration of aspirin 80-100mg failed to decrease both HR below 1. In addition, aspirin 160mg decreased the risk for preeclampsia <34 WG. No significant increase for aspirin-related complications, such as bleeding or thrombocytopenia, or other obstetrical outcomes was observed with the higher dose of aspirin.

Conclusion: The use of 160 mg aspirin for the prevention of hypertensive disorders of pregnancy may offer superior outcomes in twin pregnancies, with no discernible rise in complications when compared to aspirin doses ranging from 80-100 mg. Further research should explore long-term impacts and refine dosage strategies for optimal outcomes in twin pregnancies.