Aspirin after spontaneous preterm birth: does the placenta pick who benefits?

Design

Secondary analysis of a randomised placebo-controlled trial (APRIL)

Population

160 women with previous spontaneous preterm birth and available placental histology

Primary outcome

Recurrent preterm birth

Effect

With malperfusion: 4.2% vs 45.0%, RR 0.09 (95% CI 0.01 to 0.43); without: RR 1.70 (0.87 to 3.56)

The Dutch APRIL trial compared low-dose aspirin with placebo in women with a previous spontaneous preterm birth. This secondary analysis retrieved placental histology from that earlier birth, which was available for 160 of 387 participants (41%), and grouped women by whether the placenta showed maternal vascular malperfusion on standard criteria.

Malperfusion was present in 44 women. Among them, preterm birth recurred in 1 of 24 on aspirin and 9 of 20 on placebo (RR 0.09, 95% CI 0.01 to 0.43). In the 116 women without malperfusion, there was no benefit: 29% on aspirin versus 17% on placebo (RR 1.70, 0.87 to 3.56).

The idea is plausible: a spontaneous preterm birth driven by placental vascular disease might respond to a drug that helps in pre-eclampsia. But this is a small subgroup of a subgroup, with histology missing for most of the trial, so chance and selection could explain much of it.

For now, this is a reason to look for the previous placental report and to discuss the uncertainty, not a basis for a new aspirin protocol.

• Check whether placental histology from a previous spontaneous preterm birth exists, and request the report.
• Note whether maternal vascular malperfusion was described.
• Discuss aspirin in a subsequent pregnancy as uncertain evidence, not a proven preterm-birth preventive.
• Keep established measures such as cervical length surveillance and progesterone where indicated.

Why it matters

It suggests one cause of spontaneous preterm birth may respond to aspirin while others do not.

Don't overread it

A post-hoc subgroup of 44 women cannot establish benefit; histology was missing for most participants.

The statistics, in plain English

The relative risk of 0.09 looks dramatic but rests on 44 women, and the confidence interval is wide (0.01 to 0.43). In women without malperfusion the interval crosses 1.0, so it neither shows benefit nor clearly shows harm. Subgroup results like this need confirming in a trial designed to test them.

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