Low-dose, short-acting, angiotensin-converting enzyme inhibitors as rescue therapy in pregnancy.

OBJECTIVE: To assess the risks and potential benefits of low-dose angiotensin-converting enzyme (ACE) inhibitor treatment in pregnancies complicated by severe hypertension. METHODS: A retrospective review of pregnant women treated with ACE inhibitors was conducted. Hemodynamics before and after treatment were assessed by using Doppler technique to measure cardiac output. Data were analyzed by using the Wilcoxon signed-rank test. Maternal and neonatal outcomes were assessed by chart review and phone interview. RESULTS: Ten pregnancies were identified in which ACE inhibitor therapy was initiated in pregnancy for severe, unresponsive vasoconstricted hypertension; three were complicated by severe chronic hypertension, 4 by renal insufficiency, and 3 by severe preeclampsia. Treatment was limited to a low-dose, short-acting ACE inhibitor (captopril, 12.5 to 25 mg/day). Treatment was associated with an increase in cardiac output from 5.7 +/- 1.5 L/minute to 7.4 +/- 1.4 L/minute (P<.01) and a reduction in total peripheral resistance from 1770 +/- 670 to 1222 +/- 271 dyne. sec. cm(-5) (P =.005). No fetal or neonatal complications were observed. The probability of observing one or more adverse neonatal outcome in this sample, based on an assumed true risk of 5% and 10%, was calculated to be 12% and 50%, respectively. CONCLUSION: Low-dose captopril therapy was associated with improvement in maternal hemodynamics and, in cases complicated by severe hypertension and renal insufficiency, successful continuation of pregnancy. Fetal and neonatal complications were not experienced, but complication rates of 5-10% could have been missed because of the small number of exposed pregnancies.

Maternal hemodynamics and pregnancy outcome in women with prior orthotopic liver transplantation.

The aim of this study is to evaluate the hemodynamics and pregnancy outcome of women with prior orthotopic liver transplantation. Hemodynamic measurements by Doppler technique were performed on pregnant subjects with prior orthotopic liver transplantation. Maternal characteristics, renal function, pregnancy complications, delivery indications, delivery mode, and neonatal outcomes were evaluated. Six pregnancies occurred in 5 women after orthotopic liver transplantation at the University of Washington Medical Center (Seattle, WA) between 1991 and 1999. Four of the 6 pregnancies were complicated by chronic hypertension, fetal growth restriction, and preterm delivery. Two pregnancies had worsening hypertension characterized by vasoconstriction in the second trimester despite antihypertensive therapy. These 2 subjects were administered cyclosporine for maintenance immunosuppression and had greater mean arterial pressures preconception and in the first trimester than the other subjects. One of these pregnancies resulted in fetal demise at 25 weeks' gestation. The other subject was delivered at 28 weeks' gestation for nonreassuring fetal status and superimposed preeclampsia. All pregnancies were complicated by renal insufficiency; however, the 2 subjects with poor obstetric outcome had preconception serum creatinine levels greater than 1.5 mg/dL and creatinine clearances less than 40 mL/min. Pregnancies complicated by second-trimester vasoconstriction and moderate renal insufficiency are at risk for preeclamspia, fetal growth restriction, and fetal demise. Good obstetric outcome can occur in women with mild renal insufficiency and well-controlled chronic hypertension. Improved hypertensive control preconception may decrease the risk for preeclampsia and poor obstetric outcome.

The maternal hemodynamic effect of indomethacin in normal pregnancy.

The vasodilation of pregnancy is thought by many to be due to increased endothelial production of prostacyclin, a vasodilatory prostanoid. Indomethacin, a potent inhibitor of prostaglandin synthesis, is known to increase the maternal blood pressure response to angiotensin II infusion. We sought to measure directly the hemodynamic effects of a short course of indomethacin. Twenty-three healthy pregnant women with uncomplicated pregnancies between 26-32 weeks' gestation completed the study. Using Doppler technology, we determined cardiac output, stroke volume, and total peripheral resistance before and after three 25-mg doses of indomethacin. Although blood pressure did not change, peripheral resistance rose and stroke volume fell following indomethacin administration. Our findings support the hypothesis that indomethacin interferes with tonic prostaglandin-induced vasodilation in pregnancy. However, the increase in vascular resistance was very slight, suggesting that other vasodilators are also at work in pregnancy. We recommend that indomethacin be used judiciously in hypertensive pregnant patients until more information concerning possible adverse hemodynamic effects becomes available.

The effect of maternal hemodynamics on fetal growth in hypertensive pregnancies.

Seventy-six pregnancies in which hypertension complicated pregnancy before 28 weeks' gestation were studied. In 36, hemodynamics were characterized by increased cardiac output and low vascular resistance; in 32, hemodynamics were characterized by high resistance; in eight hemodynamics crossed over from high output to high resistance during pregnancy. High-resistance hypertension was associated with a mean birth weight 1058 gm less than that in the low-resistance group (p = 0.001). The reduction in birth weight was due to a 4-week difference in gestational age (p = 0.001) and lower percentile weights for gestational age, 19th versus 39th (p = 0.005). Infants in the crossover group had low percentile weights and a high rate of intrauterine fetal death.

Measurement of cardiac output in pregnancy by Doppler technique.

Doppler technique of measuring cardiac output was evaluated during pregnancy. In a study of accuracy Doppler technique correlated well with thermodilution, (r = 0.95, y = 1.05x - 0.35). In a study of interoperator variability, the technique was found to be reproducible, (r = 0.92, y = 0.91x + 0.74).