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.

Project Start
1988-04-01
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Parker Jr, C R; Hauth, J C; Goldenberg, R L et al. (2000) Umbilical cord serum levels of thromboxane B2 in term infants of women who participated in a placebo-controlled trial of low-dose aspirin. J Matern Fetal Med 9:209-15
Hauth, J C; Goldenberg, R L; Parker Jr, C R et al. (1995) Low-dose aspirin: lack of association with an increase in abruptio placentae or perinatal mortality. Obstet Gynecol 85:1055-8
Wenstrom, K D; Hauth, J C; Goldenberg, R L et al. (1995) The effect of low-dose aspirin on pregnancies complicated by elevated human chorionic gonadotropin levels. Am J Obstet Gynecol 173:1292-6
Hauth, J C; Goldenberg, R L; Parker Jr, C R et al. (1995) Maternal serum thromboxane B2 reduction versus pregnancy outcome in a low-dose aspirin trial. Am J Obstet Gynecol 173:578-84
Copper, R L; Goldenberg, R L; Dubard, M B et al. (1995) Cervical examination and tocodynamometry at 28 weeks' gestation: prediction of spontaneous preterm birth. Am J Obstet Gynecol 172:666-71
Atkinson, M W; Maher, J E; Owen, J et al. (1994) The predictive value of umbilical artery Doppler studies for preeclampsia or fetal growth retardation in a preeclampsia prevention trial. Obstet Gynecol 83:609-12
Hauth, J C; Goldenberg, R L; Parker Jr, C R et al. (1993) Low-dose aspirin therapy to prevent preeclampsia. Am J Obstet Gynecol 168:1083-91;discussion 1091-3
DuBard, M B; Goldenberg, R L; Copper, R L et al. (1993) Are pill counts valid measures of compliance in clinical obstetric trials? Am J Obstet Gynecol 169:1181-2
Owen, J; Maher, J E; Hauth, J C et al. (1993) The effect of low-dose aspirin on umbilical artery Doppler measurements. Am J Obstet Gynecol 169:907-11
Maher, J E; Owen, J; Hauth, J et al. (1993) The effect of low-dose aspirin on fetal urine output and amniotic fluid volume. Am J Obstet Gynecol 169:885-8

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