Low-dose aspirin started in early pregnancy reduces preterm delivery in low-resource settings, and the practical questions that follow are when exactly to start it and how hard to chase adherence. This post hoc analysis of a large randomised trial addressed both. Outcomes were available for 11,908 of 11,943 women randomised between 6 weeks 0 days and 13 weeks 6 days at hospitals across Africa, Asia and Latin America. Medication was supplied in two-week packs with pill counts every fortnight; median gestational age at initiation was 10.1 weeks, and 85.5% of women had adherence above 90%.
Neither variable modified the treatment effect. For each additional week of gestational age at initiation, the treatment risk ratio was unchanged for preterm delivery (0.97, 95% CI 0.93 to 1.02), for preterm delivery before 34 weeks (0.98, 0.89 to 1.07), and for perinatal mortality (1.04, 0.96 to 1.12). For each 5% increase in adherence, again nothing: 1.01, 0.99 and 1.02 respectively. There was no effect modification by region.
That is reassuring in two directions. A woman who books at 13 weeks rather than 7 has not missed the window — the benefit does not depend on starting at the earliest possible moment within this range. And the substantial minority whose adherence is imperfect are still getting the benefit, so aspirin does not need to be perfectly taken to work.
Be careful about what this does not say. Adherence was high overall, with 85.5% of women above 90%, so the analysis had limited range to detect an effect of poor adherence — it says little about a woman taking a third of her tablets. And the whole analysis is confined to initiation between 6 and 13 weeks; it offers no support for starting aspirin at 20 weeks, which is a separate and much less favourable question.
For Indian antenatal practice, where first booking frequently happens later than ideal, the useful message is not to abandon aspirin because the woman presented at 12 weeks rather than 8, and not to spend the consultation on adherence anxiety when there are more consequential things to check.
- Start low-dose aspirin at any point between 6 and 13 weeks; later initiation within that window did not reduce benefit.
- Do not withhold aspirin from a woman booking at 12 or 13 weeks on the grounds that it is too late.
- Imperfect adherence still delivered benefit — reinforce it, but do not treat it as pass or fail.
- This says nothing about starting aspirin after 14 weeks, which was outside the trial.
- Adherence was high overall, so the analysis cannot speak to severely poor adherence.
The statistics, in plain English
This is an interaction analysis, which asks a subtler question than whether a drug works: it asks whether the size of the effect differs across levels of something else. Interaction tests need far more data than main-effect tests, which is why they usually fail to find anything even when a real difference exists — so a null interaction is weaker evidence than a null main effect. Here the intervals are tight (0.93 to 1.02 for initiation timing), which strengthens the conclusion, and the analysis is post hoc, meaning the question was asked after the data were seen.
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