PLoS Medicine (Feb 2022)

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial.

  • Anadeijda J E M C Landman,
  • Marjon A de Boer,
  • Laura Visser,
  • Tobias A J Nijman,
  • Marieke A C Hemels,
  • Christiana N Naaktgeboren,
  • Marijke C van der Weide,
  • Ben W Mol,
  • Judith O E H van Laar,
  • Dimitri N M Papatsonis,
  • Mireille N Bekker,
  • Joris van Drongelen,
  • Mariëlle G van Pampus,
  • Marieke Sueters,
  • David P van der Ham,
  • J Marko Sikkema,
  • Joost J Zwart,
  • Anjoke J M Huisjes,
  • Marloes E van Huizen,
  • Gunilla Kleiverda,
  • Janine Boon,
  • Maureen T M Franssen,
  • Wietske Hermes,
  • Harry Visser,
  • Christianne J M de Groot,
  • Martijn A Oudijk

DOI
https://doi.org/10.1371/journal.pmed.1003892
Journal volume & issue
Vol. 19, no. 2
p. e1003892

Abstract

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BackgroundPreterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth.Methods and findingsWe performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth ConclusionsIn this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth.Trial registrationDutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.