Journal Club Papers
There is no doubt aspirin prevents preterm preeclampsia. And by doing this, it is likely to reduce overall rates of preterm birth, medically indicated ones.
Interesting data is emerging that suggests aspirin can prevent spontaneous preterm birth, even if preeclampsia is not involved. This has clinical relevance as it could become a new tool to prevent spontaneous preterm birth, perhaps added to progesterone or cervical cerclage.
The following complementary papers examine whether low-dose aspirin reduces the risk of another episode of preterm birth among women with a history of preterm birth. One is an RCT, the other a large linkage study. Both point in the same direction, suggesting aspirin may reduce the spontaneous preterm birth risk.
Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial. Landam et al. PLOS Medicine. Feb 2022
- This multicentre, double-blinded, placebo-controlled trial randomised 406 women with a singleton pregnancy and a history of spontaneous preterm birth.
- Women were randomised to 80 mg of aspirin (n=204) or placebo (n=202) starting at 8 – 16 weeks’ gestation. Aspirin was continued until 36 weeks’ gestation.
- 387 women were included in the final analysis.
- Preterm birth <37 weeks’ gestation occurred in 21.1% (41/194) of women in the aspirin group and in 25.4% (49/193) in the placebo group.
- While there was a trend - 17% reduced risk - aspirin was not associated with a significantly reduced risk of spontaneous preterm birth; relative risk 0.83 (95% CI 0.58 to 1.20, p-value 0.32).
- There were no differences between treatment groups for gestational age at birth, preterm birth <34 and <28 weeks gestation, mode of delivery, postpartum haemorrhage, and the incidence of small for gestational age neonates.
- Serious adverse events were equal in both group (5.4%)
The obvious limitation is that the sample size was underpowered. The authors anticipated a preterm birth rate of 35%, but the actual rate was only 25%, and this rendered the study underpowered. It is therefore possible (though still unknown) that the 17% reduced relative risk would have been significant if the trial had recruited larger numbers.
Low dose aspirin use in pregnancy and the risk of preterm birth: a Swedish register-based cohort study. Kupka et al. AJOG. September 2022
Review contributed by Dr Rangi De Silva.
- This next paper harnessed the power of large datasets to examine the association between low dose aspirin and the risk of preterm birth.
- This Swedish registry-based cohort study included pregnant women who had suffered a previous preterm birth.
- The primary outcome was the risk of recurrent preterm birth in the second pregnancy (spontaneous or medically indicated), according to aspirin use.
- Low-dose aspirin use was defined as one or more prescriptions during pregnancy. Doses dispensed were 75 – 160mg.
- The study included 22,127 pregnant women who had a previous preterm birth. In this second pregnancy, 3,057 women (14%) were prescribed aspirin and 19,070 (86%) were not.
- Aspirin was associated with a 13% reduced risk of overall preterm birth (both medically indicated and spontaneous), with an adjusted marginal relative risk (mRR) of 0.87 (95% CI 0.77-0.99).
- The incidence of preterm birth in the second pregnancy was 17.9% among women using aspirin and 16.6% for women not using aspirin.
- Stratifying by onset of preterm birth, low dose aspirin was associated with a reduced risk of spontaneous preterm birth (mRR 0.70 95% CI 0.57-0.86), but not medically indicated preterm birth (mRR 1.09 95% CI 0.91-1.30).
This study suggests low-dose aspirin may be an effective prophylaxis for preterm birth. Interestingly, it appeared to only work to prevent spontaneous preterm birth (but not medically indicated births), where the risk reduction may be as much as 30%. Further large studies are needed to validate these encouraging findings. In summary, both papers suggest low dose aspirin may be effective in reducing the risk of spontaneous preterm birth, but further studies are needed before it is used for this indication.