Journal club papers
Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial. Hoffman et al. Lancet (25/01/2020)
- Randomised, placebo-controlled trial of aspirin to prevent preterm birth, recruiting across 6 low- and middle-income countries.
- 11,976 nulliparous women randomised to receive 81 mg of aspirin or placebo, starting 6+0 – 13+6 weeks gestation until 36 weeks, or delivery.
- Women assigned to aspirin were 11% less likely to give birth before 37 weeks gestation (Relative risk 0.89 [95% confidence interval 0.81-0.98]).
- Overall, women were 25% less likely to give birth before 34 weeks (RR 0.75 [95% CI 0.61-0.93]; 3.3% vs. 4.0%).
- The incidence of women giving birth <34 weeks with a hypertensive disorder was decreased by 62% in the aspirin group (RR 0.38 [95% CI 0.17-0.85]; 0.1% vs. 0.4%).
- Perinatal mortality was reduced among the aspirin group (RR 0.86 [95% CI 0.73-1.00]).
- The overall incidence of hypertensive disorders of pregnancy were no different between groups (may be underpowered).
Interpretation/things to consider:
- The data provides strong validation that aspirin prevents preterm preeclampsia. There were also encouraging benefits, such as reduced perinatal mortality.
- Despite administering 81 mg the rate reduction of preterm birth (62% for <34 weeks) was similar to the ASPRE trial (also 62% for <37 weeks) which used 150 mg of aspirin (Rolnick NEJM 2017). It suggests doses around 75-100 mg may be enough to prevent preterm preeclampsia.
- While unclear, the reduced rates of preterm birth were probably driven by decreasing rates of preeclampsia. However, it is an intriguing thought that aspirin can prevent preterm birth unrelated to preeclampsia.
- It was conducted in low-middle income countries where the baseline rates of preterm birth are high (13.1% among placebo). Thus while we believe the data supports the beneficial actions of aspirin we do not think it means aspirin should be liberally given to all nulliparous women in well-resourced settings. Please be aware there is a small but significant postpartum bleeding risk associated with aspirin (see Duley et al. Cochrane Review 2019). Hence aspirin may only be beneficial if the original risk of developing preeclampsia is increased.
- A randomized trial to determine whether planned caesarean birth results in a lower risk of adverse perinatal outcomes than planned vaginal birth for twin pregnancies.
- Women with a twin pregnancy (first twin cephalic) were randomised between 32+0 and 38+6 for either planned caesarean (1398 women) or planned vaginal delivery (1406 women).
- Elective delivery was planned to happen between 37+5 and 38+6
- 89.9% of the planned caesarean group underwent caesarean delivery for both twins (59.2% prior to labour); 56.2% of the planned vaginal delivery group had a vaginal birth of both twins, 4.2% had a combined vaginal birth-caesarean and the remainder (39.6%) were delivered by caesarean section.
- The time from randomization to delivery was shorter in the planned caesarean group, and the mean gestational age at delivery was lower in the planned caesarean group (p=0.01)
- The primary outcome – a composite of fetal or neonatal death or serious neonatal morbidity – was not significantly different between the groups (OR 1.16; 95%CI 0.77-1.74)
- The authors concluded that in twin pregnancy between 32+0 and 38+6weeks gestation, planned caesarean delivery did not significantly decrease or increase the risk of serious adverse neonatal morbidity compared with planned vaginal delivery.
- For this secondary analysis of data from the 2013 Twin Birth Study, the cohort was divided according to whether the twins were preterm or term at birth so the outcomes for those who arrived at term could be assessed.
This new re-analysis showed:
Preterm: for twins at 32+0 – 36+6 weeks gestation (n=2 630 twins), planned vaginal birth trended towards fewer adverse outcomes compared to planned caesarean birth (OR 0.62; 95%CI 0.37-1.03).
Term gestation: from 37+0 onwards (n=2 932 twins), the risk of perinatal adverse outcome was two-fold greater after planned vaginal birth than planned caesarean birth (OR 2.25; 95%CI 1.06-4.77).
- Maternal and pregnancy characteristics, including maternal age, parity, history of previous caesarean, twin chorionicity, estimated fetal weights of each twin etc, were not found to be associated with a difference in outcome between the groups
- Not surprisingly, gestational age at delivery was significantly associated with risk of adverse perinatal outcome (later gestational age = lower risk)
The authors offer a more moderate conclusion compared to the original Twin Birth Study: that ‘from 32-37 weeks, a planned vaginal delivery seems favourable, while from around 37 weeks on, planned caesarean delivery might be safer’ but that the absolute risks at term are low and must be weighed against the increased maternal risks associated with planned CS.