Pregnancy-associated hypertensive disorders (PAH) are responsible for numerous maternal deaths and at least 100 perinatal deaths nationally each day. PAH may occur due to derangements in eicosanoid production Since inhibitors of eicosanoid production can ameliorate or even prevent PAH, we propose a randomized double- blinded trial of 60 mg aspirin (ASA) or placebo daily (beginning at 24 weeks' gestation) in 600 otherwise healthy nulliparous women. Patient compliance, possible mechanisms of action of ASA, and normalcy of the fetoplacental unit will be evaluated by measurements of salicylate, thrombin-induced platelet production of malondialdehyde, TXB, 6-keto-PGF, progesterone and estriol in maternal blood each 4 weeks from 24 weeks' gestation until delivery. We also will evaluate the possibility that altered deoxycorticosterone formation from plasma progesterone is predictive of which women will develop PAH. Such maternal samples also will e resource for future analyses of other potential predictive markers of PAH. The pathophysiology of PAH, as well as a possible mechanism of the efficacy of aspirin in preventing PAH, will be further assessed by placental bed biopsies in patients requiring cesarean delivery. Tissue will be viewed with light microscopy to assess the integrity of the placental spiral arteries as well as the extent of their trophoblastic invasion. Every 4 weeks from 24 weeks until delivery, fetal growth and development will be determined by ultrasound parameters (biparietal diameter femur length head circumference, four-quadrant measurement of amniotic fluid and placental grading), and pulse and continuous doppler estimation of uterine and umbilical arterial flow will be measured. newborns will be assessed with a routine clinical exam to include percentiles of fetal growth parameters. Evaluation for persistent fetal circulation will be performed when indicated, and all newborns will be assessed for alterations in hemastosis. We will also quantify umbilical venous and arterial levels of salicylate TXB, 6-keto-PGH, and markers of the fetal hypothalamic- pituitary-adrenal axis.
Showing the most recent 10 out of 11 publications
