Low-dose aspirin inhibits lipid peroxides and thromboxane but not prostacyclin in pregnant women

328

Citations from the Literature

postnatal age. Results: Fetal RCC were usually at the vascular pole of the most mature glomeruli within the deeper areas of the cortex and were occasionally located within glomeruli. This distribution persisted until birth, even when the kidney was histologically mature. By contrast there were fewer RCC in neonatal and infant kidneys and, as in adult kidneys, these were located predominantly in the superftcial cortex. Conclusion: The change in RCC distribution around the time of normal birth may relate to the transition to independent renal function. The location and density of RCC during fetal life may influence renal perfusion and amiotic fluid production. Maternal aod fetal atria1 ?atriuretic ? peptide levels at delivery from normal and growth retarded pregnancies

Kingdom JCP; McQueen J; Connell JMC; Whittle MJ Department of Fetal Medicine, Birmingham Maternity Hospital, Birmingham BI5 2TG. GBR

BR J OBSTET GYNAECOL 1992 99/10 (845-849) Objective: To determine whether circulating fetal levels of the vasodilator atrial natriuretic peptide (ANP) are reduced in pregnancies complicated by intrauterine growth retardation (IUGR). Design: Prospective observational study. Setting: University teaching hospital and research laboratory. Subjects: 25 normal singleton pregnancies delivered at term by spontaneous vertex delivery (n = 16) or by elective cesarean section (n= 9), and a series of 14 singleton pregnancies complicated by IUGR. Intervention: Measurement of ANP by radio-immunoassay in maternal venous, umbilical artery, and umbilical vein plasma from a series of normal, and IUGR pregnancies. Main outcome measures: Comparison of plasma ANP levels between the three groups; relation between fetal ANP, PO* and pH. Results: Mode of delivery did not influence either maternal, umbilical artery or umbilical vein plasma ANP levels in normal term singleton pregnancies. Umbilical vein ANP levels were significantly higher in the IUGR group when compared with normal pregnancies at term (mean 66 95%, CI 36-122 vs. mean 37, 95% CI 29-47 pgrnl, P = 0.03) and were inversely related to umbilical artery pH (R’ = 65%; P = 0.003). Conclusions: These data suggest that umbilical vein ANP levels are elevated in pregnancies complicated by IUGR, and rise appropriately in response to the stress of acidosis. In the absence of any receptor or second messenger defect within feto-placental vascular smooth muscle, these data suggest that ANP is not directly implicated in the vascular pathophysiology of IUGR. Neonatal periven~iculu-intraven~iculnr hemorrhage after maternal #J-sympatbomimetic tocolysis Groome LJ; Goldenberg RL; Cliver SP; Davis RO; Copper RL Division of Maternal-Fetal Medicine, Department of Obstetrics/ Gynecology, University of South Alabama, 2451 Fillingim St., Mobile, AL 36617, USA

AM J OBSTET GYNECOL 1992 167/4 I (873-879) Objective: Our objective was to determine if the rate of periventricular-intraventricular hemorrhage is increased in the offspring of women who received a &sympathomimetic agent as part of the management of preterm labor. Study design: This retrospective study consists of 2827 women who were delivered Int J Gynecoi Obstet 41

of a singleton, live infant free of congenital neurologic anomalies between 25 and 36 completed weeks of gestation during a multicenter preterm birth prevention trial. The data were analyzed, adjusting for type of tocolytic agent, race, infant sex, gestational age, birth weight, health care center, route of delivery, indication for delivery, intrapartum fetal distress, respiratory distress syndrome, and neonatal sepsis. Results: The overall incidence of periventricular-intraventricular hemorrhage in this populatien was 5.6%. In a univariate analysis in which no adjustment was made for potentially confounding variables, &sympathomimetic tocolysis was found to be associated with nearly a fourfold increase in the incidence of periventricular-intraventricular hemorrhage when compared with the use of either magnesium sulfate or no tocolytic agent. The results of a multivariate regression analysis revealed that j3sympathomimetic agents were associated with a statistically significant increase in the overall incidence of periventricularintraventricular hemorrhage (odds ratio 2.47, 95% confidence interval 1.34 to 4.56, P = 0.004) and a similar, but not significant, increase in the incidence of grades 3 and 4 periventricularintraventricular hemorrhage (odds ratio 2.50, 95% confidence interval 0.96 to 6.48, P = 0.06). Conclusion: gSympathomimetic tocolytic therapy may be associated with a more than twofold increase in the incidence of neonatal p&ventricular-intraventricuar hemorrhage. A randomized prospective comparison of aifedipine and bed rest versusbed restalone ia the management of preechmpsia remote from term

Sibai BM; Barton JR; Akl S; Sarinoglu C; Mercer BM 853 Jefferson Ave., Memphis, TN 38103. USA AM J OBSTET GYNECOL 1992 167/4 I (879-884) Objective: The objective of our study was to test the hypothesis that treatment with nifedipine for mild preeclampsia remote from term reduces the number of days of maternal hospitalization and improves pregnancy outcome. Study design: A total of 200 patients at 26 to 36 weeks’ gestation were randomly allocated to treatment with either bed rest alone (n = 100) or bed rest in combination with nifedipine (n = 100). Results: Patients receiving nifedipine had significantly lower systolic (P < 0.0001) and diastolic (P < 0.0001) blood pressures during therapy. Severe hypertension as an indication for delivery was significantly (P < Q.05) more frequent in the bed-rest-alone group. The two study groups had similar average days of maternal hospitalization (12.6 f 7.9 vs 12.3 f 10.3) and pregnancy prolongation (22.3 f 13.5 vs. 22.5 f 15.7). There were no differences between groups with respect to birth weight, incidences of small-for-gestational-age infants and preterm birth, number of days spent in special care unit, or cord blood gas measurement. Conclusion: Nifedipine therapy for preeclampsia reduces maternal blood pressure but does not reduce number of days of maternal hospitalization or improve perinatal outcome. Low-dose aspirin inhibits lipid peroxides and thromboxaw not prostacyclin ia pregnant women

Walsh SW; Wang Y; Kay HH; McCoy MC

bat

Citations from the Literature Medical College of Virginia, Department of Obstetrics/Gynecology. Box 34, MCV Station, Richmond, VA 23298-0034, USA

AM. J OBSTET GYNECOL 1992 16714I (926-930) Objective: Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin and an abnormal increase of lipid peroxides. Lipid peroxides are toxic compounds that damage cells and inhibit prostacyclin synthesis. Low-dose aspirin therapy reduces the incidence of preeclampsia, presumably by selective inhibition of thromboxane to restore a balance between thromboxane and prostacyctin. However, the effectiveness of low-dose aspirin might also relate to inhibition of lipid peroxides. Study design: To test this hypothesis, 10 women at risk of preeclampsia were placed on low-dose aspirin therapy (81 mg/day) between 9 and 34 weeks of gestation. Plasma samples were collected before and after 3 to 4 days and 3 to 4 weeks of aspirin therapy. Samples were analyzed for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites, thromboxane B2 and 6keto-prostaglandin F( lo), and for lipid peroxides by hydrogen peroxide equivalents. Results: Low-dose aspirin significantly decreased (P < 0.05) both lipid peroxides (130 * 18 vs. 92 f 11 and 68 * 9 nmol/ml, mean f SE) and thromboxane (502 f 67 vs. 138 f 67 and 8 f 5 pgAnl), but it did not affect prostacyclin (55 f 10 vs. 41 i 8 and 40 f 11 pgAnl, P > 0.1). Conclusion: Low-dose aspirin selectively inhibits both lipid peroxides and thromboxane without affecting prostacyclin. Inhibition of both lipid peroxides and thromboxane by low-dose aspirin reveals a new mechanism of action and may account for its effectiveness in the prevention of preeclampsia. M~R&IBI sulfate therapy in preeclampsia is associated with increawd urinary cyclic fgmnohe monopbmpbte excretion Barton JR; Sibai BM; Ahokas RA; Whybrew WD; Mercer BM Antenatal Diagnostic Division, Central Baptist Hospital, 1740 Ncholawille Road, Lexington, KY 40503, USA

AM J OBSTET GYNECOL 1992 167/4 I (931-934) Objective: Our objective was to determine if maternal urinary cyclic guanosine monophosphate levels are altered in preeclampsia. Study design: Aliquots from 24-h urine samples collected from 57 women with preeclampsia and 14 normotensive pregnant women in the third trimester of pregnancy were assayed for urinary cyclic guanosine monophosphate. Urinary cyclic guanosine monophosphate values were expressed per milligram of urinary creatinine to standardize for renal function. Results: There was no difference in gestational age at time of urine collection between the two groups. Urinary cyclic guanosine monophosphate levels (mean * SD.) were similar between normotensive and preeclamptic pregnant women (751 f 498 vs. 632 f 363 pmol/mg urinary creatinine, respectively, P = 0.12). Preeclamptic women receiving magnesium sulfate had signiticantly higher levels of urinary cyclic guanosine monophosphate than those not receiving magnesium sulfate (786 360 vs. 555 344 pmoUmg urinary creatinine, respectively, P = 0.02). Conclusions: These preliminary results indicated that cyclic guanosine monophosphate excretion increases in patients with preeclampsia during magnesium sulfate infusion. The vascular smooth muscle relaxation effects of magnesium sulfate

329

may be mediated by directly increasing cyclic guanosine monophosphate production or indirectly through endotheliumderived relaxing factor. PIaeeMaIIipidperoxidesandtbron~boxaneareincreasedandpre!itacyeIIa Is &XXe&XdIn women with PreeelarnpaIa Wang Y; Walsh SW, Ray HH Medical College of Virginia, Department of Obstetrics/Gynecology, Box 34, MCV Station, Richmond, VA 23298-0034,

USA

AM J OBSTET GYNECOL 1992 167/4 I (946-949) Objective: There is an imbalance of increased thromboxane and decreased prostacyclin in placentas of women with preeclampsia, but this may not be the only imbalance. There is also an abnormal increase in serum lipid peroxides in preeclamptic women. Lipid peroxides are toxic compounds that damage cells and inhibit prostacyclin synthesis. The following study examined lipid peroxides to determine if they were also increased in placentas of preeclamptic women. Study design: Placental tissue for nine normal and eight preeclamptic women were frozen in liquid nitrogen immediately after delivery. Frozen tissue samples (1 gm) were homogenized and analyzed for lipid peroxides by malondialdehyde and hydrogen peroxide equivalents and for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites, thromboxane B, and 6keto prostaglandin F&Y). Results: Lipid peroxides were significantly higher in preeclamptic placentas than in normal placentas by both analytic methods (49 f 5 vs. 31 ?? 1 nmoUgm for malondialdehyde and 5.3 ?? 0.3 vs. 3.2 f 0.3 pmol/gm for hydrogen peroxide equivalent; mean + SE; P < 0.01, respectively). Thromboxane was significantly higher and prostacyclin significantly lower in preeclamptic placentas than in normal placentas (213 f 23 vs. 158 f 14 ng/gm for thromboxane and 24 f 3 vs. 53 f 7 r&m for prostacyclin, P < 0.05). The thromboxane/prostacyclin and lipid peroxides/prostacychn ratios were threefold higher in preeclamptic placentas than in normal placentas. Conclusion: Placental levels of both lipid peroxides and thromboxane are increased and prostacyclin decreased in preeclampsia. We speculate that abnormally increased levels of lipid peroxides in preeclamptic placentas may be a cause of decreased prostacyclin. Nifedipine treatment in preeclampsia reverts tbe increased erythcyte aggregatbn to normal Tranquilli AL; Garxetti GG, De Tommaso G, Boemi M; Lucino E; Fumelli P, Romanini C PO Box 51, 60100 Ancona. ITA AM J OBSTET GYNECOL 1992 167/4 I (942-945) Objectives: Our objectives were to assess erythrocyte aggregation in hypertensive pregnancy and to evaluate the effect of the antihypertensive treatment on it. Study design: The mean entity of erythrocyte aggregation was determined by an automatic aggregometer in 57 pregnant women: 20 normotensive, seven chronically hypertensive, 10 chronically hypertensive with superimposed preeclampsia, and 20 with preeclampsia. Ten of the latter were subsequently treated by 40 mg/day oral nifedipine; the other 10 by 400 mg/day oral labetalol, to keep diastolic blood pressure ~90 mm Hg. Also, Int J Gynecol Obstet 41