The brain study: Cognition, quality of life and social functioning following preeclampsia; An observational study.

OBJECTIVES: Previously preeclamptic women may express cognitive difficulties, which have largely been unappreciated or attributed to stresses of a complicated pregnancy. This study aimed to explore the scope of perceived neurocognitive and psychosocial problems as well as quality of life following preeclampsia. STUDY DESIGN: Observational study. Through website promotion and e-mail, registrants of the USA-based Preeclampsia Foundation who experienced preeclampsia in the past 20years were invited to complete a web-based survey. Participants were requested to ask an acquaintance that had a normotensive pregnancy to also complete the survey (controls). MAIN OUTCOME MEASURES: The Cognitive Failures Questionnaire (CFQ), abbreviated WHO Quality Of Life questionnaire (WHOQOL-BREF), Social Functioning Questionnaire (SFQ) and Breslau Short Screening Scale for DSM-IV Posttraumatic Stress Disorder were used in the survey. Analysis was performed using Mann-Whitney U tests and linear regression. RESULTS: 966 cases and 342 controls completed the survey (median age 34, median time since first pregnancy 4 vs. 5years). Cases scored significantly worse on CFQ (median 35 vs. 27), WHOQOL-BREF domains physical health (15 vs. 17), psychological (13 vs. 15), social relationships (13 vs. 15) and environment (15 vs. 16), and SFQ (8 vs. 7). All p<0.001. Multivariable analysis showed an independent significant effect of eclampsia on CFQ and of migraine on all questionnaires and the effect of preeclampsia was still present after adjustment for confounders. Posttraumatic stress symptoms accounted for part of the relationships. CONCLUSIONS: Previously preeclamptic women appear to perceive more cognitive and social problems, and report poorer quality of life compared to a group of women with normotensive pregnancies. Research relating to the origin and management of these issues is needed.

Preeclampsia and risk of developing subsequent diabetes.

OBJECTIVE: Determine whether preeclampsia is associated with developing diabetes. METHODS: Subsequent diabetes was ascertained using ICD-9 codes, pharmacy and glucose data in a retrospective cohort study of 2,032 women with preeclampsia and 29,431 without preeclampsia. RESULTS: During a median follow-up of 8.2 years, 342 women developed diabetes. Preeclampsia was associated with a higher risk of diabetes adjusting for age, primigravidity, and gestational diabetes (hazard ratio, HR 1.82, 95%CI 1.26, 2.62) and in women without gestational diabetes (n = 30,109; HR 1.86, 95%CI 1.22, 2.84). CONCLUSION: Women with preeclampsia have greater risk of developing diabetes, even in the absence of gestational diabetes.

Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice.

Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, beta-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were approximately 50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 +/- 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable beta-cell responsivity indices, the average beta-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.

Clonidine pharmacokinetics in pregnancy.

The objective of this study was to determine the pharmacokinetic parameters of clonidine during pregnancy compared with previously published data in nonpregnant subjects. Serial blood and urine samples were collected in 17 women during mid to late pregnancy over one steady-state dosing interval to determine clonidine noncompartmental pharmacokinetic parameters (n = 17) and creatinine clearance. In six of these pregnant subjects, maternal and umbilical cord (venous and arterial) plasma samples were collected at the time of delivery for measurement of clonidine concentrations. Clonidine apparent oral clearance was found to be 440 +/- 168 ml/min during pregnancy compared with 245 +/- 72 ml/min as previously reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There was a strong correlation (r = 0.82, p < 0.001) between clonidine renal clearance, adjusted for variation in glomerular filtration rate, and urine pH. Umbilical cord to maternal plasma clonidine concentration ratios were 1.0 +/- 0.1 (arterial) and 1.0 +/- 0.1 (venous). In conclusion, clonidine is cleared more rapidly in pregnant women than in nonpregnant subjects. At the time of delivery, the fetus is exposed to similar plasma clonidine concentrations as the mother.

Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: a University of Washington specialized center of research study.

The objectives of the study were to evaluate the effects of pregnancy on CYP3A and P-glycoprotein (P-gp) activities, as measured by disposition of midazolam and digoxin, respectively. Thirteen women received digoxin (0.25 mg p.o.) and midazolam (2 mg p.o.) in random order, separated by 1-2 weeks at 28-32 weeks gestation, and the same order was repeated at 6-10 weeks postpartum. Plasma and urine concentrations were determined by liquid chromatography-mass spectrometry and analyzed by noncompartmental methods. Midazolam CL/F(unbound) (593 +/- 237 l/min vs. 345 +/- 103 l/min; P = 0.007), digoxin CL(Renal, unbound) (272 +/- 45 ml/min vs. 183 +/- 37 ml/min; P < 0.002) and digoxin CL(secretion,) (unbound) (109 +/- 34 ml/min vs. 58 +/- 22 ml/min; P < 0.002) were higher during pregnancy than postpartum. These data are consistent with increased hepatic and/or intestinal CYP3A and renal P-gp activities during pregnancy.

Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies.

Amoxicillin is recommended for anthrax prevention in pregnancy. The objective of this study was to evaluate the pharmacokinetics of amoxicillin during pregnancy and postpartum (PP). Sixteen women received amoxicillin during gestation (18-22 weeks (T2) and 30-34 weeks (T3)) as well as 3 months postpartum (PP) to evaluate single-dose pharmacokinetics. Amoxicillin compartmental pharmacokinetic parameters were used to simulate amoxicillin concentration-time profiles following different dosage strategies. Amoxicillin CL(renal) (T2: 24.8+/-6.7 l/h, P<0.001; T3: 24.0+/-3.9 l/h, P<0.001; and PP: 15.3+/-2.6 l/h) and renal CL(secretion) (T2: 280+/-105 ml/min, P<0.002; T3: 259+/-54 ml/min, P<0.001; and PP: 167+/-47 ml/min) were higher during pregnancy than postpartum. Simulations suggest that amoxicillin concentrations adequate to prevent anthrax may be difficult to achieve during pregnancy and postpartum. Increases in amoxicillin CL(renal) and renal CL(secretion) reflect increases in filtration and secretory transport or diminished reabsorption in the kidneys. Amoxicillin may not be an appropriate antibiotic for post-anthrax exposure prophylaxis.

Treatment of hypertension in pregnancy: effect of atenolol on maternal disease, preterm delivery, and fetal growth.

OBJECTIVE: To assess the impact of antihypertensive therapy initiated early in pregnancy on maternal and fetal outcomes. METHODS: A retrospective review of patients treated in early pregnancy with atenolol was conducted. Therapy was directed by measurements of cardiac output. Fetal growth was analyzed with reference to prior pregnancy outcome, treatment inconsistent with standards present at the end of the study period, and year of treatment. Data were analyzed by paired and unpaired t-test, analysis of variance for multiple comparisons, and linear regression. RESULTS: Two hundred thirty-five pregnancies at risk for preeclampsia were studied. Ten percent (n = 22) received additional therapy with furosemide; 20% (n = 48) with hydralazine. Six and one half percent had treatment inconsistencies. Fifty-five percent had greater than 100 mg of proteinuria at baseline. One patient developed severe preeclampsia. Only 2.1% delivered before 32 weeks; 4.7% delivered before 34 weeks. Low percentile birth weight was strongly associated with a prior pregnancy with intrauterine growth restriction (P = 0.001), treatment inconsistency (P <.001), and a pregnancy earlier in our treatment experience (P <.001). Percentile birth weight increased from the 20th at the beginning of the study period to the 40th by the end (P = 0.002). CONCLUSION: Early intervention with antihypertensive therapy was associated with a low rate of severe maternal hypertension and preterm delivery. The failure to adjust therapy in response to an excessive fall in cardiac output or increase in vascular resistance was associated with reduced fetal growth.

Risk of uterine rupture during labor among women with a prior cesarean delivery.

BACKGROUND: Each year in the United States, approximately 60 percent of women with a prior cesarean delivery who become pregnant again attempt labor. Concern persists that a trial of labor may increase the risk of uterine rupture, an uncommon but serious obstetrical complication. METHODS: We conducted a population-based, retrospective cohort analysis using data from all primiparous women who gave birth to live singleton infants by cesarean section in civilian hospitals in Washington State from 1987 through 1996 and who delivered a second singleton child during the same period (a total of 20,095 women). We assessed the risk of uterine rupture for deliveries with spontaneous onset of labor, those with labor induced by prostaglandins, and those in which labor was induced by other means; these three groups of deliveries were compared with repeated cesarean delivery without labor. RESULTS: Uterine rupture occurred at a rate of 1.6 per 1000 among women with repeated cesarean delivery without labor (11 women), 5.2 per 1000 among women with spontaneous onset of labor (56 women), 7.7 per 1000 among women whose labor was induced without prostaglandins (15 women), and 24.5 per 1000 among women with prostaglandin-induced labor (9 women). As compared with the risk in women with repeated cesarean delivery without labor, uterine rupture was more likely among women with spontaneous onset of labor (relative risk, 3.3; 95 percent confidence interval, 1.8 to 6.0), induction of labor without prostaglandins (relative risk, 4.9; 95 percent confidence interval, 2.4 to 9.7), and induction with prostaglandins (relative risk, 15.6; 95 percent confidence interval, 8.1 to 30.0). CONCLUSIONS: For women with one prior cesarean delivery, the risk of uterine rupture is higher among those whose labor is induced than among those with repeated cesarean delivery without labor. Labor induced with a prostaglandin confers the highest risk.

First-birth cesarean and placental abruption or previa at second birth(1).

OBJECTIVE: To assess the association between first-birth cesarean delivery and second-birth placental abruption and previa. METHODS: We conducted a population-based, retrospective cohort analysis using data from the Washington State Birth Events Record Database. The study cohort included all primiparas who gave birth to live singleton infants in nonfederal short-stay hospitals from January 1, 1987, through December 31, 1996, and who had second singleton births during the same period (n = 96,975). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for placental abruption or previa at second births associated with first-birth cesareans. RESULTS: Among our study cohort, abruptio placentae complicated 11.5 per 1000 and placenta previa 5.2 per 1000 singleton deliveries at second births. In logistic regression analyses adjusted for maternal age, women with first-birth cesareans had significantly increased risk of abruptio placentae (OR 1.3, 95% CI 1.1, 1.5), and placenta previa (OR 1.4, 95% CI 1.1, 1.6) at second births, compared with women with prior vaginal deliveries. CONCLUSION: We found moderately increased risk of placental abruption and previa as a long-term effect of prior cesarean delivery on second births.

Cesarean delivery and postpartum mortality among primiparas in Washington State, 1987-1996(1).

OBJECTIVE: To examine the association between delivery method and mortality within 6 months of delivery among primiparas. METHODS: We conducted a population-based, retrospective cohort analysis using statewide, maternally linked birth certificate, hospital discharge, and death certificate data. The present cohort was all primiparas who gave birth to live-born infants in civilian hospitals in Washington State from January 1, 1987 through December 31, 1996 (n = 265,471). Odd ratios (OR) and 95% confidence intervals (CI) were calculated for overall mortality, pregnancy-related mortality, and pregnancy-unrelated mortality associated with delivery method. RESULTS: Thirty-two women (12.1 per 100,000 singleton live births) died within 6 months of delivery of their first child. Eleven of 32 deaths were pregnancy related (4.1 per 100,000 singleton live births, 95% CI 1.6, 6.5), and 21 of the 32 deaths were not pregnancy related (7.9 per 100,000 singleton live births, 95% CI 4.5, 11.3). The pregnancy-related mortality rate was higher among women delivered by cesarean (10.3/100,000) than among women delivered vaginally (2.4/100,000). In logistic regression analyses, women who had cesarean delivery were not at significantly higher risk of death overall after adjustment for maternal age (OR 1.7, 95% CI 0.3, 3.6), pregnancy-related death after adjustment for maternal age and severe preeclampsia (OR 2.2, 95% CI 0.6, 7.9), or pregnancy-unrelated death after adjustment for maternal age and marital status (OR 0.9, 95% CI 0.3, 2.7), relative to women who had vaginal delivery. CONCLUSION: Cesarean delivery might be a marker for serious preexisting morbidities associated with increased mortality risk rather than a risk factor for death in and of itself. Data from additional sources such as medical records and autopsy reports are necessary to disentangle preexisting mortality risk from risk associated solely with delivery method.

The relationship between hemodynamics and inflammatory activation in women at risk for preeclampsia.

OBJECTIVE: This study evaluated: 1) whether women with risk factors for preeclampsia had a hyperdynamic circulation and increased markers of endothelial and inflammatory activation; and 2) whether hemodynamically directed therapy was associated with a change in markers. METHODS: A controlled experimental study was performed for two groups: 1) women at risk for preeclampsia (high risk); and 2) women at low risk (controls). Tumor necrosis factor-alpha (TNF-alpha), TNF-alpha receptors 1 and 2, vascular cell adhesion molecule-1, cellular fibronectin, and cardiac output were measured at or before 24 weeks' gestation and at 6-8 week intervals. High-risk subjects with cardiac output greater than 7.4 L/minute were treated with atenolol. Atenolol therapy was not randomized. Therefore, the longitudinal data were descriptive. Data were analyzed by the t test, Wilcoxon rank sum test, chi(2) test, multivariable linear regression, and the standard two-stage test. RESULTS: There were 46 high-risk subjects and 25 controls. Maternal age, gestational age, and parity did not differ between the groups. Cardiac output (P <.001) and vascular cell adhesion molecule-1 (P =.02) at baseline were significantly increased in the high-risk group. A total of 42 women in the high-risk group received atenolol for high cardiac output. There was a slower rise in TNF-alpha receptor 1 in the treated group compared with the controls (P <.001). CONCLUSION: Women with risk factors for preeclampsia had a hyperdynamic circulation and endothelial activation. Hemodynamically directed therapy in women at risk was associated with a slower rise in TNF-alpha receptor 1 compared with low-risk women who were not treated, suggesting a relationship between hemodynamics and inflammatory activation.

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.

Association between method of delivery and maternal rehospitalization.

CONTEXT: Despite nearly 4 million deliveries in the United States each year, minimal information exists on unintended health consequences following childbirth, particularly in relation to delivery method. OBJECTIVE: To assess the risk for maternal rehospitalization associated with cesarean or assisted vaginal delivery compared with spontaneous vaginal delivery. DESIGN: Retrospective cohort study of data from the Washington State Birth Events Record Database for 1987 through November 1, 1996. SETTING AND PARTICIPANTS: All primiparous women without selected chronic medical conditions who delivered live singleton infants in nonfederal short-stay hospitals in Washington State (N =256,795). MAIN OUTCOME MEASURES: Relative risks (RRs) of rehospitalization within 60 days of cesarean or assisted vaginal vs spontaneous vaginal deliveries. RESULTS: A total of 3149 women (1.2%) were rehospitalized within 60 days of delivery. In logistic regression analyses adjusting for maternal age, rehospitalization was found to be more likely among women with cesarean delivery (RR, 1.8; 95% confidence interval [CI], 1.6-1.9) or assisted vaginal delivery (RR, 1.3; 95% CI, 1.2-1.4) than among women with spontaneous vaginal delivery. Cesarean delivery was associated with significantly increased risks of rehospitalization for uterine infection, obstetrical surgical wound complications, and cardiopulmonary and thromboembolic conditions. Among women with assisted vaginal delivery, significant increased risks were seen for rehospitalization with postpartum hemorrhage, obstetrical surgical wound complications, and pelvic injury. CONCLUSIONS: Women with cesarean and assisted vaginal deliveries were at increased risk for rehospitalization, particularly with infectious morbidities. Effective strategies for preventing and controlling peripartum infection should be an obstetrical priority.

Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition.

Nine healthy males participated in a double-blind, placebo-controlled, randomized, crossover study to determine the effects of verapamil and metoprolol administered alone and concurrently on blood flow through the hepatic artery and portal and hepatic veins and to detect a possible drug interaction between the two agents. Single oral doses of placebo/placebo, metoprolol (50 mg)/placebo, verapamil (80 mg)/placebo, or verapamil/metoprolol were separated by at least 14 days. Liver blood flow through individual hepatic vessels was measured up to 8 hours after dosage administration using a duplex Doppler ultrasound technique. Cardiac output, heart rate, blood pressure, stroke volume, and total peripheral resistance were measured for 3 hours after drug doses were given. In 5 subjects, pharmacokinetic parameters for total drug as well as S- and R-enantiomers were also measured. Verapamil given alone caused a rapid and intense increase in liver blood flow (hepatic artery = 50%, portal vein = 42%, hepatic vein = 55%) 0.75 to 1 hour after administration because of a decrease in total peripheral resistance and an increase in heart rate, stroke volume, and cardiac output. Metoprolol given alone caused a slow but prolonged decrease in liver blood flow (maximum decrease: hepatic artery = -54%, portal vein = -21%, hepatic vein = -27%) 4 hours after administration because of a decrease in heart rate and cardiac output. When the two agents were given together, a composite of the changes noted after separate administration was noted: a brief peak increase in liver blood flow at 0.33 to 1 hour followed by a slow, prolonged decrease that reached its maximum decline 4 to 5 hours postdose. During the combined phase, metoprolol and its enantiomers had an increased AUC and Cmax, while verapamil and its enantiomers had an increased AUC and t1/2. These pharmacokinetic changes were consistent with the magnitude and time course of liver blood flow changes through the hepatic artery and portal or hepatic veins.

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.

Pulmonary hypertension in pregnancy: treatment with pulmonary vasodilators.

OBJECTIVE: To describe the clinical course of pregnancies complicated by pulmonary hypertension and treated with the pulmonary vasodilators nifedipine and prostacyclin. METHODS: Four pregnant women with pulmonary hypertension were treated with pulmonary vasodilators. Therapy with oral nifedipine and intravenous prostacyclin was guided by right pulmonary artery catheterization and Doppler measurements of cardiac output. RESULTS: Three of four women responded to vasodilator therapy and successfully completed their pregnancies. Two who conceived at least 1 year after successful treatment and normalized right ventricle function carried three uncomplicated pregnancies. The woman who did not respond died. Delay in diagnosis contributed to her outcome. Noninvasive measurement of cardiac output helped diagnosis of right ventricular failure and offered reassurance in women who remained compensated. Postpartum decompensation in one woman was characterized by a negative Starling response as central venous pressure increased from 4 to 11 mmHg. She responded positively to diuresis. CONCLUSION: Early diagnosis of pulmonary hypertension is critical. Volume overload postpartum might significantly contribute to decompensation. We recommend a year of successful therapy after a response to vasodilator therapy and near-normal right ventricular function before pregnancy is considered. In complicated pregnancies, women must balance the best estimate of risk with the value they put on pregnancy.

Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension.

OBJECTIVE: To determine if assessment of maternal hemodynamics could predict women at risk for the development of preeclampsia, if treatment directed at hemodynamic abnormalities before the onset of hypertension could prevent preeclampsia, and if mothers could be treated in a way that protects fetal growth. METHODS: A double-blinded, randomized controlled trial was conducted. Subjects were considered to be at risk for preeclampsia if their cardiac output was greater than 7.4 L/min before 24 weeks' gestation. Nulliparous and diabetic subjects at risk were treated with 100 mg of atenolol or placebo. Cardiac output was measured by Doppler technique. Inulin and para-aminohippurate clearances were performed. RESULTS: Treatment with atenolol reduced the incidence of preeclampsia from 5 of 28 (18%) to 1 of 28 (3.8%), (P = .04). Nulliparous women determined to be at risk for preeclampsia were similar to diabetic women at risk. Each was significantly heavier and had inulin and para-aminohippurate clearances greater than the control group. Treatment with atenolol was associated with infants weighing 440 g less than infants in the nulliparous placebo group, (P = .02). No effect on birth weight was seen in the diabetic patients. Mothers of the smallest infants who were treated with atenolol could be identified by unexpectedly large reductions in cardiac output. CONCLUSION: Measurement of cardiac output in the second trimester identified women at risk for preeclampsia. Treatment with atenolol decreased the incidence of preeclampsia. Nulliparous and diabetic women at risk for preeclampsia were similar with regard to maternal hemodynamics, maternal weight, and renal function. Treatment with atenolol was associated with reduced infant birth weight.

The central and renal hemodynamic effects of amino acid infusion in the study of renal reserve in the baboon.

Normal human renal function is characterized by a large renal reserve. Recruitment of this reserve is a compensatory and pathological response to renal injury. This study was designed to assess the renal reserve and central hemodynamics of young female baboons and, in doing so, the appropriateness of the use of these animals in a model of human renal disease. Eight female baboons completed the protocol. PAH and inulin clearances were measured before and after an amino acid infusion. Central hemodynamics were measured with arterial and pulmonary artery catheters. Effective renal plasma flow and glomerular filtration rate increased by 42% after amino acid infusion (P = .025). Expansion of renal function was not consistent among individual baboons; two of the eight animals did not demonstrate renal reserve. Central hemodynamics were unaffected by the protocol.

A randomized controlled trial of the effect of third-trimester calcium supplementation on maternal hemodynamic function.

OBJECTIVE: To determine the effect of third-trimester calcium supplementation on maternal hemodynamic function. METHODS: Pregnant women were randomized to receive either 1.5 g of elemental calcium or placebo for 6 weeks during the third trimester. Using Doppler technique, maternal hemodynamic characteristics were measured at baseline, at 2 hours after the first dose of study drug, and at the completion of 6 weeks. Serum, dietary, and urinary calcium levels were also assessed. Power calculation indicated the need to study ten subjects in each group to detect a 1.2 L (20%) difference in cardiac output between groups, assuming a mean of 6.2 +/- 1.0 L/minute. Data were analyzed by analysis of variance for repeated measures, Student t test, Mann-Whitney U test, and Fisher exact test. RESULTS: Twenty-three women enrolled, and 18 completed the study. There were no statistically significant differences in demographic characteristics or in serum, dietary, or urinary calcium levels between the two groups. There were also no statistically significant differences in hemodynamic function over time within the calcium supplementation or placebo group (P > .05; analysis of variance for repeated measures). After 6 weeks, there were no significant differences between the calcium- and placebo-treated subjects in any hemodynamic measurement. Specifically, there was not a statistically significant difference in cardiac output (7.3 +/- 1.2 L/minute versus 8.0 +/- 0.9 L/minute; P = .09) between the calcium- and placebo-treated groups. CONCLUSION: These findings suggest that third-trimester calcium supplementation does not significantly alter cardiac output. The mechanism by which calcium supplementation lowers blood pressure remains to be elucidated.