Randomised comparison of uterine artery Doppler and aspirin (100 mg) with placebo in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 2). Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results: a multicenter randomised controlled trial.
To assess the effectiveness of a pre-eclampsia prevention strategy based on routine uterine artery Doppler flow velocity waveform examination during the second trimester of pregnancy, followed by a prescription for 100 mg aspirin in the case of abnormal Doppler findings.
                Multicentre randomised controlled trial.
                Eleven centres in the north of France and one in Belgium.
                One thousand and eight hundred and fifty-three nulliparous women recruited between 14 and 20 weeks of gestation.
                Randomisation either to undergo a uterine Doppler examination between 22 and 24 week of gestation or to take a placebo. Women with abnormal Doppler waveforms received 100 mg of aspirin daily from Doppler examination through 36 weeks.
                Pre-eclampsia was defined as hypertension (> or = 140 and/or 90 mmHg) associated with proteinuria (> or = 0.5 g/L).
                One thousand two hundred and fifty-three women (67%) were randomised into the systematic Doppler group and 617 (33%) into the placebo group. Of the 1175 patients in the Doppler group who underwent this examination, 239 (20.3%) had abnormal uterine artery Doppler and received a prescription for aspirin. Despite the aspirin prescription, the frequency of pre-eclampsia did not differ between the systematic Doppler group and the placebo group (28 of 1237 [2.3%] vs 9 of 616 [1.5%]; RR = 1.55, 95% CI 0.7-3.3). Furthermore, the groups did not differ in the frequency of children who were very small for their gestational age (< or =3rd centile) or for perinatal deaths. Compared with patients with normal Doppler findings, those with abnormal Doppler were at high risk of pre-eclampsia (RR = 5.5, 95% CI 2.5-12.2) and of giving birth to a small-for-gestational-age child (RR = 3.6, 95% CI 1.6-8.1).
                Despite its sensitivity in screening for pre-eclampsia, routine uterine Doppler in the second trimester cannot be recommended for nulliparous patients. To assess whether systematic screening with an uterine artery Doppler in low risk pregnant women followed by the prescription of low dose aspirin in cases with abnormal results reduced the incidence of intrauterine growth restriction and pre-eclampsia.
                A multicentre randomised trial.
                3,317 low risk pregnant women. In the Doppler group, the uterine artery Doppler was performed between 20 and 24 weeks. Women with abnormal results received 100 mg of aspirin daily until the 35th week.
                Intrauterine growth restriction was defined as birthweight below the tenth and the third centile according to gestational age. Pre-eclampsia was defined as hypertension associated with proteinuria > 0.5g/L.
                Intrauterine growth restriction, whether defined by the third or tenth centile, did not differ significantly between the two groups (RR = 1.22 [0.73 - 2.04] and 1.18 [0.93 - 1.51] respectively). Screening with uterine artery Doppler did not affect birthweight or any of the criteria of perinatal morbidity. There was no effect on the incidence of pre-eclampsia (RR = 1.99 [0.97 - 4.09]) or hypertensive disorders. These results were the same for nulliparae and multiparae.
                There is no justification for screening with uterine artery Doppler in a low risk population, even if abnormal results are followed by aspirin treatment and increased prenatal surveillance. Future studies must assess predictive tests that can be performed early in pregnancy and can identify populations at very high risk of pre-eclampsia and intrauterine growth restriction. Only when all of these conditions are fulfilled, aspirin or other treatments may prove its efficacy.
Present evidence failed to show any benefit to either the baby or the mother when utero-placental Doppler ultrasound was used in the second trimester of pregnancy in women at low risk for hypertensive disorders. Nevertheless, this evidence cannot be considered conclusive with only two studies included. There were no randomised studies in the first trimester, or in women at high risk. More research is needed to investigate whether the use of utero-placental Doppler ultrasound may improve pregnancy outcome.