RESUMEN
OBJECTIVE: To determine the effectiveness and economic impact of two methods for induction of labour in hypertensive women, in low-resource settings. DESIGN: Cost-consequence analysis of a previously reported multicentre, parallel, open-label randomised trial. SETTING & POPULATION: A total of 602 women with a live fetus, aged ≥18 years requiring delivery for pre-eclampsia or hypertension, in two public hospitals in Nagpur, India. METHODS: We performed a formal economic evaluation alongside the INFORM clinical trial. Women were randomised to receive transcervical Foley catheterisation or oral misoprostol 25 mcg. Healthcare expenditure was calculated using a provider-side microcosting approach. MAIN OUTCOME MEASURES: Rates of vaginal this delivery within 24 hours of induction, healthcare expenditure per completed treatment episode. RESULTS: Induction with oral misoprostol resulted in a (mean difference) $20.6USD reduction in healthcare expenditure [95% CI (-) $123.59 (-) $72.49], and improved achievement of vaginal delivery within 24 hours of induction, mean difference 10% [95% CI (-2 to 17.9%), P = 0.016]. Oxytocin administration time was reduced by 135.3 minutes [95% CI (84.4-186.2 minutes), P < 0.01] and caesarean sections by 9.1% [95% CI (1.1-17%), P = 0.025] for those receiving oral misoprostol. Following probabilistic sensitivity analysis, oral misoprostol was cost-saving in 63% of 5,000 bootstrap replications and achieved superior rates of vaginal delivery, delivery within 24 hours of induction and vaginal delivery within 24 hours of induction in 98.7%, 90.7%, and 99.4% of bootstrap simulations. Based on univariate threshold analysis, the unit price of oral misoprostol 25 mcg could feasibly increase 31-fold from $0.24 to $7.50 per 25 mcg tablet and remain cost-saving. CONCLUSION: Compared to Foley catheterisation for the induction of high-risk hypertensive women, oral misoprostol improves rates of vaginal delivery within 24 hours of induction and may also reduce costs. Additional research performed in other low-resource settings is required to determine their relative cost-effectiveness. TWEETABLE ABSTRACT: Oral misoprostol less costly and more effective than Foley catheter for labour induction in hypertension.
Asunto(s)
Ahorro de Costo/estadística & datos numéricos , Trabajo de Parto Inducido/métodos , Misoprostol/administración & dosificación , Oxitócicos/administración & dosificación , Parto , Cateterismo Urinario , Administración Oral , Adolescente , Adulto , Análisis Costo-Beneficio , Femenino , Gastos en Salud/estadística & datos numéricos , Humanos , India , Trabajo de Parto Inducido/economía , Misoprostol/efectos adversos , Misoprostol/economía , Oxitócicos/efectos adversos , Oxitócicos/economía , Preeclampsia/terapia , Embarazo , Resultado del Tratamiento , Cateterismo Urinario/efectos adversos , Cateterismo Urinario/economía , Adulto JovenRESUMEN
OBJECTIVE: To compare magnesium sulphate concentrations achieved by intramuscular and intravenous regimens used for the prevention of eclampsia. SETTING: Low-resource obstetric hospitals in Nagpur and Vellore, India. POPULATION: Pregnant women at risk for eclampsia due to hypertensive disease. METHODS: A pharmacokinetic study was performed as part of a randomised trial that enrolled 300 women comparing intramuscular and intravenous maintenance regimens of magnesium dosing. Data from 258 enrolled women were analysed in the pharmacokinetic study. A single sample was drawn per woman with the expectation of using samples in a pooled data analysis. MAIN OUTCOME MEASURES: Pharmacokinetic parameters of magnesium distribution and clearance. RESULTS: Magnesium clearance was estimated to be 48.1 dl/hour, volume of distribution to be 156 dl and intramuscular bioavailability to be 86.2%. The intramuscular regimen produced higher initial serum concentrations, consistent with a substantially larger loading dose. At steady state, magnesium concentrations in the intramuscular and intravenous groups were comparable. With either regimen, a substantial number of women would be expected to have serum concentrations lower than those generally held to be therapeutic. CONCLUSIONS: Clinical implications were that a larger loading dose for the intravenous regimen should be considered; where feasible, individualised dosing of magnesium sulphate would reduce the variability in serum concentrations and might result in more women with clinically effective magnesium concentrations; and lower dose magnesium sulphate regimens should be considered with caution.
Asunto(s)
Anticonvulsivantes/farmacocinética , Eclampsia/prevención & control , Sulfato de Magnesio/farmacocinética , Preeclampsia/tratamiento farmacológico , Adolescente , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Disponibilidad Biológica , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Intramusculares , Sulfato de Magnesio/administración & dosificación , Sulfato de Magnesio/uso terapéutico , Tasa de Depuración Metabólica , Embarazo , Adulto JovenRESUMEN
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.
RESUMEN
INTRODUCTION: Magnesium sulfate is the agent of choice for the treatment and prevention of eclampsia. Optimal loading and maintenance dosing has not been determined. OBJECTIVES: To compare the pharmacokinetic parameters if IM vs. IV magnesium sulfate. METHODS: A pharmacokinetic study was performed as part of a randomized trial that enrolled 300 women comparing IM and IV regimens of magnesium dosing in two low resource sites in India. Data from 258 enrolled women were analyzed in the pharmacokinetic study. Due to infrastructure available at the sites, a single sample was drawn per subject with the expectation of utilizing samples in a pooled data analysis. RESULTS: Magnesium clearance was estimated via pharmacokinetic modeling to be 48.1dL/h, volume of distribution 156dL and IM bioavailability 86.2%. The IM regimen produced higher initial serum concentrations, consistent with a substantially larger loading dose. At steady state, Mg concentrations in the IM and IV Groups were comparable. With either regimen, a substantial number of subjects would be expected to have serum concentrations lower than those generally expected to be therapeutic. CONCLUSION: A larger loading dose for the IV regimen should be considered. Where feasible, individualized higher doses of magnesium sulfate would yield a greater number of treated women with clinically effective magnesium concentrations.
RESUMEN
INTRODUCTION: Previously preeclamptic women may express cognitive difficulties, which have largely been ignored or attributed to the stresses of a complicated pregnancy. OBJECTIVES: This study aimed to identify the scope of neurocognitive and psychosocial problems following preeclampsia. METHODS: Through website promotion and a mass e-mail members of the USA-based Preeclampsia Foundation who experienced preeclampsia in the past 20 years were invited to complete a web-based survey, consisting of a questionnaire about current and past medical health, the Cognitive Failures Questionnaire (CFQ), the abbreviated WHO Quality Of Life questionnaire (WHOQOL-BREF), and the Social Functioning Questionnaire (SFQ). Participants were stimulated to ask a friend who had a normotensive pregnancy to complete the survey as well (controls). Women with current or past neurological conditions were excluded. Analysis was performed using Mann Whitney U test and linear regression. RESULTS: 966 cases and 342 controls were included. Median age was 34, median time since first pregnancy 4 and 5 years respectively. Cases scored significantly worse on all three questionnaires, and more often underwent psychiatric therapy, currently or in the past. There was a significant effect of migraine on all questionnaires and of eclampsia on CFQ score. Cronbach's alphas were >0.7, indicating good internal consistency of the questionnaires. Results are expressed as median (range) or number (percentage) (∗)p<.001. CONCLUSION: Previously preeclamptic women report more cognitive and social problems, and worse quality of life compared to women who had normotensive pregnancies. Health care providers and patients should be aware of this so that affected women may receive recognition, psychological care and escape from the ignorance of their environment. Our findings may stimulate research relating to the origin and management of these important issues.
RESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2/etiología , Diabetes Gestacional/metabolismo , Preeclampsia/metabolismo , Factores de Edad , Glucemia/metabolismo , Estudios de Cohortes , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Clasificación Internacional de Enfermedades , Embarazo , Estudios Retrospectivos , RiesgoRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Gestacional/tratamiento farmacológico , Gliburida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Adulto , Área Bajo la Curva , Hidrocarburo de Aril Hidroxilasas , Glucemia/análisis , Citocromo P-450 CYP2C9 , Relación Dosis-Respuesta a Droga , Femenino , Sangre Fetal/química , Gliburida/farmacocinética , Humanos , Hipoglucemiantes/farmacocinética , Resistencia a la Insulina , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/fisiología , Tasa de Depuración Metabólica , Método de Montecarlo , Embarazo , Tercer Trimestre del EmbarazoRESUMEN
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.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacocinética , Clonidina/farmacocinética , Hipertensión/tratamiento farmacológico , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Agonistas alfa-Adrenérgicos/sangre , Agonistas alfa-Adrenérgicos/uso terapéutico , Adulto , Área Bajo la Curva , Clonidina/sangre , Clonidina/uso terapéutico , Femenino , Semivida , Humanos , Hipertensión/complicaciones , EmbarazoRESUMEN
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.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Citocromo P-450 CYP3A/metabolismo , Digoxina/farmacocinética , Midazolam/farmacocinética , Periodo Posparto/metabolismo , Embarazo/metabolismo , Adulto , Anestésicos Intravenosos/farmacocinética , Ansiolíticos/farmacocinética , Antiarrítmicos/farmacocinética , Área Bajo la Curva , Cardiotónicos/farmacocinética , Creatinina/orina , Digoxina/sangre , Digoxina/orina , Inhibidores Enzimáticos/farmacocinética , Femenino , Cromatografía de Gases y Espectrometría de Masas , Genotipo , Humanos , Hipnóticos y Sedantes/farmacocinética , Midazolam/sangre , Midazolam/orina , Tercer Trimestre del Embarazo/metabolismoRESUMEN
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.
Asunto(s)
Amoxicilina/administración & dosificación , Amoxicilina/farmacocinética , Penicilinas/administración & dosificación , Penicilinas/farmacocinética , Embarazo/metabolismo , Adolescente , Adulto , Algoritmos , Área Bajo la Curva , Simulación por Computador , Femenino , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Método de Montecarlo , Segundo Trimestre del Embarazo/metabolismo , Tercer Trimestre del Embarazo/metabolismoRESUMEN
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.
Asunto(s)
Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Desarrollo Embrionario y Fetal/efectos de los fármacos , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Adulto , Gasto Cardíaco , Desarrollo Embrionario y Fetal/fisiología , Femenino , Edad Gestacional , Hemodinámica , Humanos , Trabajo de Parto Prematuro/etiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Trabajo de Parto Inducido/efectos adversos , Trabajo de Parto , Rotura Uterina/etiología , Parto Vaginal Después de Cesárea/efectos adversos , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Incidencia , Embarazo , Complicaciones del Embarazo , Prostaglandinas/efectos adversos , Estudios Retrospectivos , Riesgo , Rotura Uterina/epidemiología , WashingtónRESUMEN
BACKGROUND: Cyclosporine is known to be excreted in breast milk, but levels in infants are not known. Post-transplant breast-feeding has been contraindicated in mothers treated with calcineurin inhibitors such as cyclosporine. CASE: A 35-year-old woman exclusively breast-fed her infant during the first 10.5 months of life while she was being treated with cyclosporine. Cyclosporine measurements in infant and maternal blood and breast milk revealed a mean breast milk/maternal blood level ratio of 84%, but undetectable levels in the infant. The infant grew and developed normally. CONCLUSION: The infant of a cyclosporine-treated mother was breast-fed exclusively during the first 10.5 months of life and did not absorb a detectable amount of the drug. Fetal growth and development were normal.
Asunto(s)
Lactancia Materna , Ciclosporina/metabolismo , Inmunosupresores/metabolismo , Trasplante de Riñón , Leche Humana/metabolismo , Trasplante de Páncreas , Complicaciones del Embarazo/terapia , Adulto , Ciclosporina/uso terapéutico , Diabetes Mellitus Tipo 1 , Femenino , Humanos , Inmunosupresores/uso terapéutico , Recién Nacido , Fallo Renal Crónico , Masculino , Periodo Posparto , EmbarazoRESUMEN
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.
Asunto(s)
Desprendimiento Prematuro de la Placenta/epidemiología , Cesárea/estadística & datos numéricos , Placenta Previa/epidemiología , Desprendimiento Prematuro de la Placenta/etiología , Adolescente , Adulto , Orden de Nacimiento , Cesárea/efectos adversos , Cesárea/métodos , Estudios de Cohortes , Intervalos de Confianza , Femenino , Humanos , Incidencia , Oportunidad Relativa , Paridad , Placenta Previa/etiología , Vigilancia de la Población , Embarazo , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Washingtón/epidemiologíaRESUMEN
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.
Asunto(s)
Causas de Muerte , Cesárea/mortalidad , Paridad , Complicaciones Posoperatorias/mortalidad , Trastornos Puerperales/mortalidad , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Edad Materna , Preeclampsia/mortalidad , Embarazo , Estudios Retrospectivos , Riesgo , Washingtón/epidemiologíaRESUMEN
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.
Asunto(s)
Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Hemodinámica/fisiología , Inflamación/sangre , Preeclampsia/tratamiento farmacológico , Preeclampsia/fisiopatología , Adulto , Antígenos CD/sangre , Gasto Cardíaco Elevado/fisiopatología , Femenino , Fibronectinas/sangre , Edad Gestacional , Humanos , Preeclampsia/inmunología , Embarazo , Receptores del Factor de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral , Factores de Riesgo , Resultado del Tratamiento , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
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.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Captopril/administración & dosificación , Hipertensión/tratamiento farmacológico , Preeclampsia/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Captopril/efectos adversos , Gasto Cardíaco/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Edad Gestacional , Humanos , Hipertensión/etiología , Preeclampsia/etiología , Embarazo , Complicaciones del Embarazo/etiología , Estudios Retrospectivos , Resistencia Vascular/efectos de los fármacosRESUMEN
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.
Asunto(s)
Parto Obstétrico , Readmisión del Paciente/estadística & datos numéricos , Adulto , Cesárea/estadística & datos numéricos , Parto Obstétrico/efectos adversos , Parto Obstétrico/métodos , Parto Obstétrico/estadística & datos numéricos , Femenino , Humanos , Funciones de Verosimilitud , Modelos Logísticos , Complicaciones Posoperatorias/epidemiología , Hemorragia Posparto/epidemiología , Embarazo , Estudios Retrospectivos , Riesgo , WashingtónRESUMEN
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.