Aspirin for preventing adverse outcomes in low risk nulliparous women with singleton pregnancies: a systematic review and meta-analysis

Objective: To assess the effects of aspirin in pregnancy for the prevention of adverse outcomes in low risk, nulliparous women with singleton pregnancies. Study design: Medline, Embase, CINAHL, the Cochrane library, Web of Science and clinicaltrials.gov were searched from inception until February 2020. Randomised controlled trials were eligible for inclusion where women were nulliparous, had singleton pregnancies and no other risk factors for pre-eclampsia such as diabetes or pre-existing hypertension. Primary outcomes were pre-eclampsia, gestational hypertension and eclampsia. Secondary outcomes included; pre-term birth, postpartum haemorrhage, antepartum haemorrhage, miscarriage, small for gestational age (SGA), fetal growth restriction (FGR), birthweight and further markers of maternal and neonatal morbidity and mortality. The results were combined into meta-analysis where appropriate. Results: Ten studies were eligible for inclusion involving 23,162 women. Two studies (involving 214 women) used aspirin doses of 100 mg, with the remainder using smaller doses. There was no significant difference found in the risk of developing pre-eclampsia between women receiving aspirin compared to no aspirin (relative risk [RR] 0.70, 95 % confidence interval [CI] 0.47–1.05, p = 0.08). Women receiving aspirin had a reduced risk of having a preterm birth <34 weeks (RR 0.50, 95 % CI 0.26−0.96, p = 0.04), and reduced risk of having a SGA neonate (RR 0.94, 95 % CI 0.89–1.00, p = 0.04). An increase in birthweight was seen when aspirin was received (mean difference 105.17 g, 95 % CI 12.38 g–197.96 g, p = 0.03) and there was no increase in risk of postpartum or antepartum haemorrhage in those receiving aspirin (RR 1.24, 95 % CI 0.90–1.71, p = 0.19 and RR 1.06, 95 % CI 0.66–1.70, p = 0.81 respectively). Conclusion: The results did not demonstrate a significant difference amongst low risk nulliparous women in the risks of pre-eclampsia or gestational hypertensive disorders with aspirin administration. Although we found significantly improved fetal growth parameters and prevention of preterm birth in women receiving aspirin, there were few eligible studies, with those included generally providing low quality evidence and many studies using aspirin doses ≤100 mg, commenced late in pregnancy. More research in the form of a high quality randomised controlled trial is needed before recommendations can be made.