Low-dose aspirin not tied to notable reduction in recurrent preterm birth, study reveals

Netherlands: A recent study found that low-dose aspirin does not significantly reduce the rate of preterm birth in women with a previous spontaneous preterm birth. However, the researchers add that a modest decrease in preterm birth with aspirin cannot be ruled out. The findings of this study were published in PLOS Medicine.

A parallel multicenter, randomized, double-blind, placebo-controlled experiment was carried out by the researchers (the APRIL study). In the Netherlands, the study was conducted in eight tertiary and twenty-six secondary care facilities. Women who were pregnant with a singleton and had a history of spontaneous preterm delivery of a singleton between the ages of 22 and 37 weeks were included in the study. Participants were given either 80 mg of aspirin per day or a placebo starting between 8 and 16 weeks of pregnancy and continuing until 36 weeks or delivery. Computer-generated randomization was used, with allocation concealment achieved by employing sequentially numbered pharmaceutical containers. The treatment allocation was kept a secret from the participants, their healthcare providers, and the researchers.

The major result was a baby born prematurely at 37 weeks of pregnancy. Poor neonatal outcome (periventricular leukomalacia > grade 1, bronchopulmonary dysplasia, necrotizing enterocolitis > stage 1, intraventricular hemorrhage > grade 2, culture-proven sepsis, retinopathy of prematurity, or perinatal mortality) were among the secondary outcomes. Analyses were carried out with the purpose to treat.

The key findings are as follow:

1. 406 women were randomly assigned to aspirin (n = 204) or placebo (n = 202) from May 31, 2016 to June 13, 2019.

2. In the end, 387 women participated in the study, with 194 receiving aspirin and 193 receiving placebo. Preterm delivery occurred in 41 (21.2%) of aspirin-treated women and 49 (25.4%) of placebo-treated women at 37 weeks.

3. Preterm birth occurred in 24 (19.2%) women with 80% medication adherence versus 30 (24.8%) women with 80% medication adherence.

4. The rate of poor newborn outcome as a composite was 4.6% (n = 9) versus 2.6% (n = 5). Serious adverse events occurred in 11 out of 204 (5.4 percent) women who were given aspirin and 11 out of 202 (5.4%) women who were given a placebo.

5. None of the major adverse events were thought to be linked to the therapy group. The key study flaw is the small sample size, which was caused by lower-than-expected preterm birth rates.

In conclusion, When compared to placebo, there was no significant reduction in recurrent preterm delivery of a singleton in women who took low-dose aspirin (80 mg) from 8 to 16 weeks to 36 weeks of pregnancy. With the current trial, a small impact of aspirin or an effect in a subset of women (e.g., with a prior early preterm delivery) cannot be ruled out.

Reference:

Landman, A. J. E. M. C., de Boer, M. A., Visser, L., Nijman, T. A. J., Hemels, M. A. C., Naaktgeboren, C. N., van der Weide, M. C., Mol, B. W., van Laar, J. O. E. H., Papatsonis, D. N. M., Bekker, M. N., van Drongelen, J., van Pampus, M. G., Sueters, M., (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. In S. J. Stock (Ed.), PLOS Medicine (Vol. 19, Issue 2, p. e1003892). Public Library of Science (PLoS). https://doi.org/10.1371/journal.pmed.1003892