LOW-DOSE ASPIRIN IN HYPERTENSIVE PREGNANT-WOMEN - EFFECT ON PREGNANCYOUTCOME AND PROSTACYCLIN THROMBOXANE BALANCE IN MOTHER AND NEWBORN

Objective To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the producti on prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants. Design Placebo controlled prospective study. Setting Departments of Obstetrics and Gynaecology, University of Hels inki, University of Oulu and Central Hospital of Middle Finland, Finla nd. Subjects Two hundred and eight pregnant women with pre-existing hy pertension or a history of severe pre-eclampsia in their previous preg nancy. Prostanoids were studied in a subgroup of 18 women. Interventio ns The women were randomised to receive ASA (50 mg/day, n = 103) or pl acebo (n = 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre-existing hypertension or the appearance of hy pertension in previously normotensive women, the appearance of protein uria and fetal growth were the main end points, but some other clinica l characteristics were also recorded. Urinary excretion of PGI2 and Tx A2 metabolites by mothers and infants and their production in umbilica l arteries in vitro were also studied. Results Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal a nencephaly (ASA group). In addition, seven women discontinued the trea tment due to urticaria (two women in ASA group), increased activity of aspartate amino tranferase in serum (one woman in both groups), or in creased bleeding time (one woman in ASA group, two women in placebo gr oup), and one woman in the placebo group was lost from follow-up. Thus the end points could be assessed in 97 women taking ASA and 100 women taking placebo. ASA did not diminish the rate of the rise of blood pr essure without (12 vs 14, respectively) or with proteinuria (9 vs 11), but fetal haemodynamic disturbances as assessed by Doppler equipment (1/44 vs 6/45 women studied, P = 0.05) and need for treatment in neona tal intensive care unit (10 vs 21, P = 0.04) were more rare in ASA gro up. ASA tended to increase the birthweight of the newborn (3348 +/- 70 7 g vs 3170 +/- 665 g, mean +/- SD, P = 0.07), but two perinatal death s occurred in ASA group. ASA prolonged the bleeding time of the mother (435 s, 210-998 s (geometric mean, range) vs 349 s, 210-690 s, P = 0. 02), but caused no extra blood loss during delivery, nor affected neon atal hemostasis. In a subgroup of mothers (ASA, n = 10; placebo, n = 8 ), ASA inhibited more than 90% of platelet TxA2-production, and caused a 65 to 80% decrease in the urinary excretion of TxA2 metabolites, bu t no decrease in the urinary excretion of PGI2 metabolites. Conclusion s ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neona tal care. It inhibited strongly maternal thromboxane A2 but not PGI2 p roduction and thus shifted the balance between PGI2/TxA2 to the domina nce of the vasodilatory, anti-aggregatory side.