Low‐Dose Aspirin in the Prevention of Recurrent Spontaneous Preterm Birth Stratified by Placental Maternal Vascular Malperfusion: Secondary Analysis of a Randomized Trial

OBJECTIVE: To evaluate the effectiveness of low-dose aspirin in the prevention of recurrent preterm birth (PTB) in women with signs of maternal vascular malperfusion (MVM) in the placenta of the previous spontaneous PTB. DESIGN: Secondary analysis of the APRIL study. SETTING: The APRIL study, conducted in 34 centres in the Netherlands, evaluated low-dose aspirin versus placebo in the prevention of recurrent PTB after spontaneous PTB. POPULATION: Women with a history of spontaneous PTB participating in the APRIL study, with available placenta histology reports from the previous spontaneous PTB. METHODS: Placental histology reports were retrieved from participating centres and categorized for presence of MVM as defined by the Amsterdam criteria. MAIN OUTCOME MEASURES: Recurrent PTB. RESULTS: Placental histology reports of the previous spontaneous PTB were available for 41.3% (160/387) of participants, and MVM was present in 27.5% (44/160). In participants with MVM, recurrent PTB occurred in 4.2% (1/24) of the aspirin group, versus in 45.0% (9/20) in the placebo group (Relative Risk (RR) 0.09; 95% Confidence Interval (CI) 0.01-0.43; p = 0.02). In participants without MVM, PTB occurred in 29.3% (17/58) in the aspirin group compared to 17.2% (10/58) in the placebo group (RR 1.70; 95% CI 0.87-3.56; p = 0.13). CONCLUSION: In women with a history of spontaneous PTB and signs of MVM in the placenta, a vascular-mediated subgroup, the use of low-dose aspirin in a subsequent pregnancy was associated with a lower rate of recurrent PTB.