Aspirin after preterm birth may help only when the placenta showed malperfusion

Design

Secondary analysis of a multicentre placebo-controlled RCT (APRIL)

Population

160 women with prior spontaneous preterm birth and available placental histology; 44 with malperfusion

Primary outcome

Recurrent preterm birth

Effect

With malperfusion: 4.2% vs 45.0%, RR 0.09 (0.01–0.43)

The Dutch APRIL trial found no overall benefit of low-dose aspirin for preventing recurrent spontaneous preterm birth. This secondary analysis looked back at placental histology from the earlier preterm birth, which was available for 160 of 387 participants.

In the 44 women whose previous placenta showed maternal vascular malperfusion, recurrent preterm birth occurred in 1 of 24 on aspirin against 9 of 20 on placebo (RR 0.09, 95% CI 0.01–0.43). In women without malperfusion the direction reversed, 29% versus 17% (RR 1.70, 0.87–3.56), though that difference was not significant.

The biology is plausible — aspirin acting on a vascular phenotype — but the numbers are tiny and placental histology was missing for most participants. Treat it as a reason to request and read placental pathology after a spontaneous preterm birth, not as a basis for prescribing.

• After a spontaneous preterm birth, check whether placental histology was sent and what it showed.
• Note any maternal vascular malperfusion in the notes for the next pregnancy's planning.
• Do not start aspirin for recurrent preterm birth prevention on this subgroup result alone.
• Aspirin given for pre-eclampsia risk remains governed by existing guidance, unaffected by this analysis.

Why it matters

It suggests spontaneous preterm birth is not one disease, and the placenta may identify who could benefit from aspirin.

Don't overread it

A post-hoc subgroup of 44 women from a trial that was neutral overall — hypothesis-generating only.

The statistics, in plain English

The relative risk of 0.09 looks dramatic, but it comes from 10 events in 44 women; the wide interval (0.01–0.43) shows how unstable that estimate is. Subgroup findings from a trial that was negative overall are often not reproduced.

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