Low dose aspirin in women with raised maternal serum alpha-fetoprotein and abnormal Doppler waveform patterns from the uteroplacental circulation

Abstract

Objective: To investigate the use of low dose aspirin in the reduction of perinatal morbidity and mortality in women with unexplained raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns.

Design: Prospective randomised controlled trial.

Setting: A tertiary referral obstetric service.

Subjects: One hundred and sixty-four women referred to our unit with raised maternal serum alpha-fetoprotein and a structurally normal fetus had abnormal uteroplacental Doppler waveform patterns at 24 weeks of gestation.

Intervention: Women were randomly allocated to two groups, receiving either low dose aspirin 75 mg (n = 76) or placebo (n = 88) daily until delivery.

Main outcome measures: Preterm labour, low birthweight, the occurrence of placental abruptions and perinatal mortality.

Results: The frequency of severely small for gestational age infants (birthweight < 5th centile) was reduced in the aspirin treated group to 16% compared with 25% in the placebo group (95% CI-21% to 13%). The frequency of delivery before 34 weeks of gestation was 26% in the aspirin group and 42% in the placebo group (95% CI--30% to 1%). The perinatal mortality was 240/1000 in the aspirin group and 320/1000 in the placebo group (95% CI--22% to 6%). None of these reductions was statistically significant. Although the frequency of placental abruptions was similar in the two groups, significantly more babies died from abruption in the aspirin treated group (91% versus 30%, 95% CI 28% to 94%). Low dose aspirin did cause a significant reduction (P = 0.008) in deaths from causes other than placental abruption.

Conclusion: This trial revealed a benefit of low dose aspirin therapy in women with raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns, but the effect was smaller than expected. Although a reduction in deaths from small preterm babies was observed, there was an increase in the number of deaths following placental abruption without a significant increase in the number of abruptions. We recommend that this should be considered before giving aspirin to these high risk women and that other investigators should specifically look for this effect.