Andrea G. Witlin

Peripartum cardiomyopathy: An ominous diagnosis ☆ ☆☆ ★

OBJECTIVE Our purpose was to review and characterize the initial presentation, etiology, and prognosis of peripartum cardiomyopathy. STUDY DESIGN Cases of peripartum cardiomyopathy confirmed by echocardiography were prospectively collected between 1986 and 1994. RESULTS A total of 28 patients without an antecedent history of heart disease were diagnosed with peripartum cardiomyopathy. Common associated disorders included preeclampsia or chronic hypertension (19), alcohol abuse (2), family history (2), and multiple tocolytic therapy (2). Five deaths occurred (18% mortality), 3 patients received heart transplants (11%), 18 continued with cardiac impairment (64%), and only 2 patients (7%) had regress on of cardiomyopathy. The perinatal mortality rate was 36 per 1000 births. Six patients had seven subsequent pregnancies; 4 patients decompensated earlier in the subsequent pregnancy, 1 patient remained well compensated on medical therapy in spite of poor systolic function and a dilated left ventricle, and 1 patient had two subsequent pregnancies without recurrence of cardiac compromise. CONCLUSION The unique hemodynamic stresses of pregnancy unmask previously undiagnosed cardiomyopathy in otherwise medically stable individuals. The prognosis for these patients is guarded.

Magnesium sulfate therapy in preeclampsia and eclampsia

Objective To review the available evidence regarding efficacy, benefits, and risks of magnesium sulfate seizure prophylaxis in women with preeclampsia or eclampsia. Data Sources The English-language literature in MEDLINE was searched from 1966 through February 1998 using the terms “magnesium sulfate,” “seizure,” “preeclampsia,” “eclampsia,” and “hypertension in pregnancy.” Reviews of bibliographies of retrieved articles and consultation with experts in the field provided additional references. Methods of Study Selection All relevant English-language clinical research articles retrieved were reviewed. Randomized controlled trials, retrospective reviews, and observational studies specifically addressing efficacy, benefits, or side effects of magnesium sulfate therapy in preeclampsia or eclampsia were chosen. Tabulation, Integration, and Results Nineteen randomized controlled trials, five retrospective studies, and eight observational reports were reviewed. The criteria used for inclusion were as follows: randomized controlled trials evaluating use of magnesium sulfate in eclampsia, preeclampsia, and hypertensive disorders of pregnancy; nonrandomized studies of historical interest; “classic” observational studies; and recent retrospective studies evaluating efficacy of magnesium sulfate therapy, using relative risk and 95% confidence intervals where applicable. Magnesium sulfate therapy has been associated with increased length of labor, increased cesarean delivery rate, increased postpartum bleeding, increased respiratory depression, decreased neuromuscular transmission, and maternal death from overdose. A summary of randomized, controlled trials in women with eclampsia reveals recurrent seizures in 216 (23.1%) of 935 women treated with phenytoin or diazepam, compared with recurrent seizures in only 88 (9.4%) of 932 magnesiumtreated women. Randomized controlled trials in women with severe preeclampsia collectively revealed seizures in 22 (2.8%) of 793 women treated with antihypertensive agents, compared with seizures in only seven of 815 (0.9%) magnesium-treated women. Conclusion The evidence to date confirms the efficacy of magnesium sulfate therapy for women with eclampsia and severe preeclampsia. However, there is a need for a randomized controlled trial to determine efficacy of magnesium sulfate therapy for women with mild preeclampsia and gestational hypertension.

Cerebrovascular disorders complicating pregnancy - Beyond eclampsia

OBJECTIVE Our purpose was to investigate the problems encountered in the diagnosis and management of cerebrovascular disorders associated with pregnancy and the puerperium. STUDY DESIGN Pregnancies complicated by cerebrovascular disorders were identified by retrospective chart review (1985 to 1995). Events associated with trauma, neoplasm, drug ingestion, and infection were excluded. RESULTS The study population comprised 24 women with a variety of cerebrovascular disorders: 14 with infarction (5 arterial, 9 venous), 6 with intracranial hemorrhage (3 anatomic malformation, 3 unknown etiology), 3 with hypertensive encephalopathy, and 1 with an unruptured aneurysm. Blood pressure reflected physical condition at presentation and did not predict diagnosis or outcome except in the 3 women with hypertensive encephalopathy. Only 4 of 14 women with infarction and 1 of 6 with intracranial hemorrhage had a diastolic blood pressure > or = 110 mm Hg. Presumption of eclampsia delayed the diagnosis in 10 women (41.7%). In addition, patient delay in seeking medical attention complicated 10 cases. After review, none of the adverse maternal outcomes were deemed preventable by earlier physician intervention. Seven maternal deaths occurred (29.2%). Neonatal outcome was related to the gestational age and the maternal condition at presentation. CONCLUSION Cerebrovascular disorders are an uncommon and unpredictable complication of pregnancy that are associated with substantial maternal and fetal mortality. Suspected eclampsia unresponsive to magnesium sulfate therapy warrants an immediate neuroimaging study. Interestingly, in women with intracranial hemorrhage, severe hypertension was not an associated predictive factor.

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: Review of 11 cases

OBJECTIVE Little information exists regarding thrombotic thrombocytopenic purpura and hemolytic uremic syndrome during pregnancy. We report a series of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome complicating pregnancy, with emphasis on diagnosis and management of this rare disorder. STUDY DESIGN Between January 1988 and February 1996, 11 women with either thrombotic thrombocytopenic purpura (n = 8) or hemolytic uremic syndrome (n = 3) were evaluated. Clinical and laboratory findings and maternal and neonatal outcomes were recorded from the medical records. RESULTS Eight of the 11 women were in the third trimester or peripartum period, and three were seen before fetal viability. Treatment included fresh-frozen plasma in all women, plasmapheresis (n = 8), packed red blood cells (n = 9), and platelet transfusions (n = 5); 1 patient required splenectomy. There were two maternal deaths. Of the 9 surviving women, 4 had chronic renal disease, 1 of whom also had residual neurologic deficit. Preterm delivery occurred in 5 of 8 pregnancies continuing beyond 20 weeks. Indications for delivery in these 5 women included worsening maternal medical disease, nonreassuring fetal testing, and spontaneous preterm labor. Six of 8 women with viable fetuses underwent cesarean delivery. These 6 infants were born in good condition without thrombocytopenia. Of the remaining 2 infants delivered vaginally, one was healthy at 35 weeks and the other was stillborn. CONCLUSION Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome complicating pregnancy is associated with high maternal mortality and long-term morbidity. Preterm delivery and intrauterine fetal death are frequent complications of these pregnancies. Improved survival after this disorder has been attributed to aggressive treatment with plasma transfusion or plasmapheresis.

The effect of magnesium sulfate therapy on the duration of labor in women with mild preeclampsia at term: A randomized, double-blind, placebo-controlled trial

OBJECTIVE The primary outcome was to determine whether magnesium sulfate therapy prolongs the duration of labor in women with mild preeclampsia. Secondary outcomes were to assess the side effects associated with magnesium sulfate therapy: hours and maximum dose of oxytocin, incidence of progression to severe preeclampsia, incidence of cesarean delivery, change in maternal hematocrit, incidence of postpartum hemorrhage, incidence of maternal infection, and Apgar scores. STUDY DESIGN Women with a diagnosis of mild preeclampsia at term were randomized to receive standard therapy during labor and for 12 hours post partum with either magnesium sulfate (n = 67) or a matching placebo solution (n = 68). RESULTS There was no difference between magnesium sulfate and placebo with respect to the primary outcome variables: total length of labor (median 17.8 hours vs 16.5 hours, p = 0.7) and length of the active phase of labor (median 5.4 hours vs 6.0 hours, p = 0.5). In addition, no difference was observed in the secondary outcome variables: hours of oxytocin use, change in hematocrit, frequency of maternal infection, progression to severe preeclampsia, incidence of cesarean delivery, and Apgar scores. Although not statistically significant, the incidence of postpartum hemorrhage was approximately fourfold greater in the magnesium sulfate group (relative risk 4.1, 95% confidence interval 0.5 to 35.4). There was a significant difference in the maximum dose of oxytocin used (13.9 +/- 8.6 mU/min with magnesium sulfate vs 11.0 +/- 7.6 mU/min with placebo, p = 0.036). CONCLUSION The use of magnesium sulfate during labor in women with mild preeclampsia at term does not affect any component of labor but did necessitate a higher dose of oxytocin.

Risk factors for abruptio placentae and eclampsia: analysis of 445 consecutively managed women with severe preeclampsia and eclampsia.

OBJECTIVE Our purpose was to characterize the clinical presentation or laboratory variables predictive of either abruptio placentae or eclampsia in women with severe preeclampsia. STUDY DESIGN Prospective collection of perinatal data from 445 consecutively managed women with severe preeclampsia and eclampsia. Univariate analysis was used to determine which of the independent variables were significantly different between the groups (abruptio placentae vs no abruptio placentae; eclampsia vs no eclampsia). Those with significant differences were then entered into multiple logistic regression analysis to determine those characteristics that were independently related to the outcome variable (abruptio placentae or eclampsia). Before multivariate analysis, the independent variables with an interval scale of measurement were converted to a dichotomous scale, with the receiver-operator characteristic curve used to determine a cutoff level. RESULTS Univariate analysis revealed statistical significance for the following variables associated with eclampsia: uric acid concentration, > 8.1 mg/dL; proteinuria (>3+); headache; visual symptoms; deep tendon reflexes >3+; serum albumin concentration, <3 mg/dL; and serum creatinine concentration, >1.3 mg/dL. However, with subsequent multivariate analysis, only headache and deep tendon reflexes >3+ remained significant. Univariate analysis for variables associated with abruptio placentae revealed an association between bleeding and platelet count <60,000/mm3. There was no association between abruptio placentae and eclampsia and systolic, diastolic, or mean arterial pressure, quantitative proteinuria, epigastric pain, bleeding, gestational age at delivery, history of preeclampsia, or chronic hypertension. CONCLUSION Quantitative proteinuria and degree of blood pressure elevation were not predictive of either abruptio placentae or eclampsia, as has previously been suggested. The greatest morbidity associated with eclampsia occurred in women with preterm gestations not receiving medical attention.

Peripartum cardiomyopathy: A longitudinal echocardiographic study

OBJECTIVE Our purpose was to determine echocardiographic trends after initial diagnosis of peripartum cardiomyopathy. STUDY DESIGN Nine women diagnosed with peripartum cardiomyopathy were prospectively recruited for a longitudinal echocardiographic study. Severe myocardial dysfunction was defined as left ventricular end-diastolic dimension > or = 60 mm + fractional shortening < or = 21%, and mild dysfunction was defined as left ventricular end-diastolic dimension < 60 mm + fractional shortening 22% to 24%. Unpaired t tests were used to compare sample means and Fishers exact test used to compare discrete variables. RESULTS All women were seen initially for pulmonary edema. Echocardiography showed decreased systolic function in all women. The mean age at diagnosis was 33.0 +/- 6.9 years. All but one woman had a diagnosis of either chronic hypertension (n = 6) or preeclampsia (n = 2). Four women were first seen ante partum and five post partum (range 1 day to 2 months). Repeat echocardiography was performed in all nine women (median 8 months, range 6 weeks to 5 years). There was no correlation between antepartum or postpartum presentation and cardiovascular status on follow-up (p = 0.3). Values for initial left ventricular end-diastolic dimension, severe versus mild dysfunction (68.3 +/- 7.2 mm vs 55.0 +/- 4.2 mm, p = 0.046), follow-up left ventricular end-diastolic dimension, severe versus mild (68.7 +/- 4.1 mm vs 52.0 +/- 5.7 mm, p = 0.002), and follow-up fractional shortening, severe versus mild (14.6% +/- 5.0% vs 28.5% +/- 9.2%, p = 0.02) are significant. Six of the seven women with severe dysfunction had stable disease in follow-up and one is awaiting heart transplant. One of the two women with mild dysfunction had disease resolution and one had stable disease. CONCLUSION Patients with severe myocardial dysfunction due to peripartum cardiomyopathy are unlikely to regain normal cardiac function on follow-up.

Placental and Fetal Growth and Development in Late Rat Gestation Is Dependent on Adrenomedullin

Abstract Adrenomedullin is a potent, endogenous vasodilator peptide synthesized and secreted by diverse locations such as adrenal glands, lungs, kidneys, vascular smooth muscle, and endothelium. Homozygous deletion of the adrenomedullin gene is embryonic lethal. We hypothesized that adrenomedullin has an important role in placental and fetal growth and development in rat pregnancy. The current study evaluated maternal systolic blood pressure, litter size, placental and pup weight, pup mortality, and placental pathology in pregnant rats following continuous in utero exposure to an adrenomedullin antagonist. Osmotic minipumps were inserted on Gestational Day 14 to continuously deliver either adrenomedullin, adrenomedullin antagonist, or vehicle control. Systolic blood pressure was recorded daily. Pregnant rats were killed on Gestational Day 15–18, 20, and/or 22 to evaluate placental development and fetal growth. The placentas were graded for the presence of necrosis in the decidua and fetal labyrinth as well as fetal vessel development in the labyrinth. A trend toward increased systolic blood pressure was noted between Gestational Days 17 and 20 in mothers treated with adrenomedullin antagonist, but the difference was not statistically significant. Antagonism of adrenomedullin function during rat pregnancy caused fetal growth restriction, decreased placental size, gross necrosis of placental margins and amniotic membranes, histologically deficient fetal vessel development in the labyrinth, and fetal edema. Adrenomedullin contributes to angiogenesis, functions as a growth factor, and helps regulate vascular tone during rat gestation.

Presentation of venous thromboembolism during pregnancy

OBJECTIVE We sought to characterize the presentation, recurrence, and outcome of venous thromboembolism during pregnancy. STUDY DESIGN We performed a 12-year, single-center, retrospective review of 38 patients with venous thromboembolism during pregnancy. The independent variables were subjected to univariate analysis (unpaired t test for normally distributed continuous variables and Fisher exact test for discrete variables). P <.05 was considered significant. RESULTS There was no significant difference for the following variables according to time of presentation (antepartum vs post partum): gestational age at delivery (37.4 +/- 6.6 wk vs 38.1 +/- 2.4 wk; P =.7), birth weight (3257 +/- 458 g vs 3093 +/- 719 g; P =.3), and mode of delivery (2 vs 4 cesarean deliveries; P =.15). There were 2 maternal deaths. All 3 women with antepartum recurrent venous thromboembolism (despite heparin prophylaxis) had findings of protein C deficiency, protein S deficiency, and lupus anticoagulant-anticardiolipin antibody, respectively. CONCLUSION The gestational age at presentation appears more equally distributed throughout gestation than previously reported. Notwithstanding limited numbers, the recurrence of venous thromboembolism despite use of prophylactic heparin therapy suggests the need to reexamine the current recommendations for heparin dosing.

Perinatal and maternal outcome following abruptio placentae.

Objective: To characterize the maternal and fetal presentation of abruptio placentae and associated maternal and fetal morbidity and mortality by mode of delivery and fetal status on admission. Study Design: Perinatal data (gestational age > 24 weeks) from women with abruptio placentae at a tertiary referral center were analyzed. For the purpose of evaluating fetal morbidity and mortality, group 1 included women with hypertensive disorders of pregnancy (preeclampsia or chronic hypertension), PROM, cocaine abuse, and > 20% abruptio placentae without regard to fetal status on admission (reassuring, nonreassuring, or stillborn). In group 1, either umbilical artery pH < 7.0, Apgar < 35, or base excess > 12 mmol/L represented perinatal hypoxia for this evaluation. Group 2 included women with stillborn fetuses on admission without regard to etiology or size of abruptio placentae. Comparisons between groups were made with one-way analysis of variance, Kruskal–Wallis, or χ2 tests; p < 0.05 was considered significant. Results: Group 1 was comprised of 342 women; 58.4% of fetuses had abnormal fetal heart rate tracings. Overall, the sensitivity of an abnormal fetal heart rate tracing to predict perinatal hypoxia was 87.2%, specificity was 33.9%, positive predictive value was 22.2%, and negative predictive value was 92.5%. Of parameters suggestive for perinatal hypoxia, 17.3% of neonates had Apgar < 35, 13.0% had umbilical artery pH < 7.0, and 9.9% had base excess > 12 mmol/L. Overall, neonatal survival was 84.7%; 12.0% of fetuses were stillborn. For those fetuses alive on admission, cesarean delivery was associated with a significant reduction in neonatal mortality: odds ratio of 0.10 (95% confidence interval: 0.05–0.20) and p = 0.0001. Group 2 was comprised of 61 women. Women presenting with a stillborn infant on admission were more likely to require transfusions and suffer the complications (disseminated intravascular coagulopathy, acute renal failure, and acute respiratory distress syndrome) than women presenting with a live fetus. Conclusion: Cesarean delivery appeared to reduce neonatal mortality. Whether emergent cesarean delivery resulted in the birth of compromised fetus cannot be evaluated from this study. Composite maternal morbidity is increased when a stillborn fetus is present on admission.