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

Autor: Landman AJEMC; Department of Obstetrics and Gynaecology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands., de Boer MA; Department of Obstetrics and Gynaecology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands., Visser L; Department of Obstetrics and Gynaecology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands., Nijman TAJ; Department of Obstetrics and Gynaecology, Haaglanden Medical Centre, Den Haag, the Netherlands., Hemels MAC; Department of Neonatal Intensive Care, Isala, Zwolle, the Netherlands., Naaktgeboren CN; Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands., van der Weide MC; Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands., Mol BW; Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia.; Aberdeen Centre for Women's Health Research, University of Aberdeen Aberdeen, United Kingdom., van Laar JOEH; Department of Obstetrics and Gynaecology, Máxima Medical Centre, Veldhoven, the Netherlands., Papatsonis DNM; Department of Obstetrics and Gynaecology, Amphia Hospital, Breda, the Netherlands., Bekker MN; Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht, the Netherlands., van Drongelen J; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands., van Pampus MG; Department of Obstetrics and Gynaecology, OLVG, Amsterdam, the Netherlands., Sueters M; Department of Obstetrics and Gynaecology, Leiden University Medical Centre, Leiden, the Netherlands., van der Ham DP; Department of Obstetrics and Gynaecology, Martini Hospital, Groningen, the Netherlands., Sikkema JM; Department of Obstetrics and Gynaecology, Hospital Group Twente Almelo, Almelo, the Netherlands., Zwart JJ; Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, the Netherlands., Huisjes AJM; Department of Obstetrics and Gynaecology, Gelre Hospitals Apeldoorn, Apeldoorn, the Netherlands., van Huizen ME; Department of Obstetrics and Gynaecology, Haga Hospital, Den Haag, the Netherlands., Kleiverda G; Department of Obstetrics and Gynaecology, Flevo Hospital Almere, Almere, the Netherlands., Boon J; Department of Obstetrics and Gynaecology, Diakonessenhuis, Utrecht, the Netherlands., Franssen MTM; Department of Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen, the Netherlands., Hermes W; Department of Obstetrics and Gynaecology, Haaglanden Medical Centre, Den Haag, the Netherlands., Visser H; Department of Obstetrics and Gynaecology, Tergooi Hospitals, Hilversum, the Netherlands., de Groot CJM; Department of Obstetrics and Gynaecology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands., Oudijk MA; Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands.
Jazyk: angličtina
Zdroj: PLoS medicine [PLoS Med] 2022 Feb 01; Vol. 19 (2), pp. e1003892. Date of Electronic Publication: 2022 Feb 01 (Print Publication: 2022).
DOI: 10.1371/journal.pmed.1003892
Abstrakt: Background: Preterm 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 Findings: We 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 <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > 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 <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates.
Conclusions: In 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 Registration: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BM reported an Investigator grant from the National Health and Medical Research Council (NHMRC; grant no. GNT1176437); receipt of research funding from Guerbet; and is a former advisory board member at ObsEva. All other authors do not report any relevant financial activities outside the submitted work.
Databáze: MEDLINE
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