Low-dose aspirin may not prevent preterm labour in high-risk women

Findings from the APRIL trial presented at SMFM 2021 fail to show substantial evidence that low-dose aspirin may reduce the recurrence of preterm birth (PTB) when initiated in early pregnancy in high-risk women (ie, women with a history of spontaneous PTB*).

“Recurrent spontaneous PTB remains a large contributor to perinatal morbidity and mortality as a result of PTB, [hence the] need for additional preventive methods,” the researchers noted previously. [BMC Pregnancy Childbirth 2017;17:223] PTB accounts for 70 percent of all neonatal mortality and 40 percent of childhood neurologic morbidity. [Early Hum Dev 1999;53:193-218] “[These may lead to] a tremendous impact on both the child and its parents.”

Owing to the promising effect of aspirin against spontaneous PTB seen in previous randomized trials on pre-eclampsia, in vitro fertilization, and miscarriage, [Obstet Gynecol 2010;116:402-414; Obstet Gynecol 2017;129:327-336; Hum Reprod 2013;28:1480-1488; N Engl J Med 2010;362:1586-1596] the investigators postulated that aspirin, when given before 16 weeks gestation onwards, may reduce the recurrence of spontaneous PTB. Moreover, aspirin has been deemed as a safe intervention in pregnancy, as per the US Preventive Services Task Force. [Ann Intern Med 2014;160:695-703]

As such, the team sought to evaluate the efficacy of aspirin in the prevention of recurrent spontaneous PTB. Between May 2016 and June 2019, 387 women were randomized 1:1 to receive daily aspirin 80 mg or placebo, initiated from 8 to 16 weeks up to a maximum of 36 weeks gestation or delivery. Eligible participants were women with a singleton pregnancy and a history of spontaneous PTB in a singleton pregnancy (between 22–37 weeks). [SMFM 2021, abstract 9]

Compared with the placebo arm, small numerical reductions were seen in the aspirin arm in terms of the incidences of PTB (21.2 percent vs 25.4 percent; relative risk [RR], 0.83, 95 percent confidence interval [CI], 0.58–1.2) and spontaneous PTB (20.1 percent vs 23.8 percent; RR, 0.84, 95 percent CI, 0.58–1.2).

The risk of PTB was also numerically lower among women on aspirin who were ≥80 percent compliant with the study drug, as opposed to the respective placebo subgroup (18.5 percent vs 24.8 percent; RR, 0.75, 95 percent CI, 0.46–1.2).

Despite the greater fraction of women having poor neonatal outcomes** in the aspirin vs the placebo arm (4.6 percent vs 2.6 percent; RR, 1.79, 95 percent CI, 0.61–5.3), no significant differences were observed in terms of maternal morbidities (eg, postpartum haemorrhage, hypertensive disease), the researchers noted.

The investigators have previously noted that since aspirin “is already widely embedded in the obstetric practice for other indications … if [it] is proven effective in reducing recurrent spontaneous PTB, it would be easy to implement in daily practice.”

“[Nonetheless, while] the small reduction of PTB from aspirin … cannot be discounted … [our current] data did not demonstrate a [significant] reduction of PTB in women with a previous SPTB who used aspirin 80 mg,” said the researchers. “[Moreover,] the RR for PTB is comparable to larger studies on aspirin in other groups of women.”