Previous delivery of low-weight babies not an indication for subsequent low-dose aspirin use

Low-dose aspirin falls short of preventing the incidence of small-for-gestational age (SGA) neonates in subsequent pregnancies, suggesting that the drug should not be used to prevent the recurrence of delivering smaller babies, according to a study.

In the Swedish register-based study, the number of SGA neonates born was similar among women who used and those who did not use low-dose aspirin (21.7 percent vs 20.7 percent). Low-dose aspirin use in pregnancy did not reduce the risk of having an SGA neonate (adjusted relative risk [aRR], 0.86, 95 percent confidence interval [CI], 0.67–1.10) or a severely SGA neonate (aRR, 0.98, 95 percent CI, 0.71–1.34) in subsequent pregnancies. [Obstet Gynecol 2022;doi:10.1097/AOG.0000000000004696]

On further analysis, considering the strong association between pre-eclampsia and SGA, low-dose aspirin use still had a null effect on the risk of having an SGA (aRR 0.83, 95 percent CI 0.63–1.10) or severely SGA (aRR 1.02, 95 percent CI 0.73–1.44) neonate among women who had an SGA neonate and co-existing pre-eclampsia in their first pregnancy. The same was true among women who developed pre-eclampsia in their second pregnancy.

“Aspirin has been shown to be an effective preventative agent for women at risk of developing pre-eclampsia. Pre-eclampsia and foetal growth restriction often coexist, and, with related placental pathologies, aspirin has been suggested to prevent foetal growth restriction or birth of an SGA neonate,” according to the investigators. [Drug Ther Bull 2021;59:56-59]

“Our data do not support previous SGA alone as an indication for subsequent aspirin use,” they added.

The findings were further supported by a large randomized controlled trial that evaluated aspirin (81 mg daily) use for the prevention of preterm birth among nulliparous women. In this trial, aspirin produced a significant decrease in the incidence of preterm birth but did not alter the risk of having an SGA neonate (RR, 0.95, 95 percent CI, 0.90–1.01). [Lancet 2020;395:285-293]

In terms of safety, previous reports showed aspirin to be associated with an increased risk of maternal bleeding, including postpartum haemorrhage and postpartum haematoma. [Am J Obstet Gynecol 2021;224:95.e1-12; Cochrane Database Syst Rev 2019;2019:CD004659]

“Thus, the use of aspirin for preventing SGA may place women at an increased risk of intrapartum and postpartum bleeding complications,” the investigators pointed out.

The present study included 8,416 women (mean age 31.1 years, mean body mass index 24.3 kg/m²) who gave birth to an SGA neonate in their first pregnancy, among whom 801 (9.5 percent) used low-dose aspirin during their second pregnancy.

Compared with unexposed women, those who used low-dose aspirin were more likely to be older, have obesity, have become pregnant through in vitro fertilization, be employed, and were less likely to smoke. Additionally, women using low-dose aspirin tended to have pregestational disorders and have had experienced complications during their first and second pregnancies.

The investigators acknowledged the presence of several study limitations, including the nongeneralizability of the findings to non-Swedish populations. Also, information on the dosage of aspirin used, indication, and adherence were not captured, leaving a potential for maternal underreporting and ascertainment bias.

“However, in Sweden, aspirin is routinely prescribed at 75 mg during pregnancy,” they said, adding that further investigations using other populations and higher doses, including 150 mg, are warranted to establish the utility of aspirin for the primary prevention of SGA.