Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin‐thromboxane balance in mother and newborn

Abstract

Objective To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production 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 Helsinki, University of Oulu and Central Hospital of Middle Finland, Finland. Subjects Two hundred and eight pregnant women with pre‐existing hypertension or a history of severe preeclampsia in their previous pregnancy. Prostanoids were studied in a subgroup of 18 women. Interventions The women were randomised to receive ASA (50 mg/day, n= 103) or placebo (n= 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre‐existing hypertension or the appearance of hypertension in previously normotensive women, the appearance of proteinuria and fetal growth were the main end points, but some other clinical characteristics were also recorded. Urinary excretion of PGI2 and TxA2 metabolites by mothers and infants and their production in umbilical arteries in vitro were also studied. Results Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal anencephaly (ASA group). In addition, seven women discontinued the treatment due to urticaria (two women in ASA group), increased activity of aspartate amino tranferase in serum (one woman in both groups), or increased bleeding time (one woman in ASA group, two women in placebo group), 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 pressure 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 neonatal intensive care unit (10 vs 21, P= 0.04) were more rare in ASA group. ASA tended to increase the birthweight of the newborn (3348 ± 707 g vs 3170 ± 665 g, mean ± SD, P= 0.07), but two perinatal deaths 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 neonatal 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, but no decrease in the urinary excretion of PGI2 metabolites. Conclusions ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neonatal care. It inhibited strongly maternal thromboxane A2 but not PGI2 production and thus shifted the balance between PGI2/TxA2 to the dominance of the vasodilatory, anti‐aggregatory side.

Platelet function in pregnant women receiving aspirin and dipyridamole

“…In this study, aspirin and dipyridamole did not prolong the bleeding time. Previous studies of patients receiving low-dose aspirin have reported prolonged bleeding time, which was not associated with clinical bleeding [15,16]. The explanation of this discrepancy is not clear, but it may be related to the lower dose of aspirin used in our study compared with other studies (40 mg vs 50-60 mg), different methods of measurement, and the small number of subjects in our study.…”

Validity in Nulliparas of Increased b-Human Chorionic Gonadotrophin at Mid-Term for Predicting Pregnancy-Induced Hypertension Complicated with Proteinuria and Intrauterine Growth Retardation

“…Low-dose aspirin has been proven to reduce the risk of pregnancy-induced hypertension (PIH) complicated with proteinuria (preeclampsia), and/or of intrauterine growth retardation, and to a lesser extent the risk of noncomplicated PIH, only in selected multiparous or mixed popula tions with a high risk of developing these complications [1][2][3][4][5][6] but not in nonselected populations with moderate risk as in the recent Italian study [7], In the pioneering study ofBeaufils et al [1] in multipa ras the selection criteria were severe vascular complica tions during the previous pregnancies (early precclampsia, in utero fetal death, abruptio placentae, pregnancy-in duced hypertension with small for gestational age (SGA) babies. The same type of criteria were used in the study of Benigni et al [2] and Uzan et al [3].…”

O Papel da Aspirina na Prevenção da Pré-Eclâmpsia: Estado da Arte

“…[28][29][30][31] A avaliação da redução do risco de restrição de crescimento fetal com o uso de aspirina foi definida como objetivo principal num estudo multicêntrico, publicado em 1991, o estudo EPREDA. 30 Concluiu que com a utilização entre as 15 -18 semanas de aspirina na dose de 150 mg, associada a dipiridamol (225 mg/dia) houve prevenção do risco de restrição de crescimento fetal, em grávidas com este antecedente.…”

“…Vinikka et al, 31 utilizando uma baixa dose (50 mg) de ácido acetilsalicílico iniciado em média às 15 semanas em mulheres com hipertensão arterial prévia à gravidez ou pré--eclâmpsia grave em gestação anterior, verificou que, em comparação com os controles, os agentes anti-plaquetá-rios não impediram a subida da pressão arterial materna, mas melhoraram os resultados fetais, com melhor resposta hemodinâmica fetal, redução de restrição de crescimento fetal e menor necessidade de internamento em unidades de cuidados intensivos neonatais. Verificaram uma forte inibição do tromboxano A2 materno, sem redução da produção de prostaciclina, preponderando portanto a dominância da ação vasodilatadora e de anti-agregação plaquetária.…”