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Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double‐blind, placebo‐controlled trial

Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth.

Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: A secondary analysis from a randomized, double-blind, placebo-controlled trial

To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester.

Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial

To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth.

Route of breech delivery and maternal and neonatal outcomes

Objective: To compare maternal and neonatal outcomes in elective cesarean vs. attempted vaginal delivery for breech presentation at or near term. Methods: We reviewed the maternal and neonatal charts of all singleton breech deliveries of at least 35 weeks’ gestation or 2000 g delivered between 1986 and 1997 at our institution. Patients delivered by elective cesarean were compared to those attempting a vaginal delivery. The neonatal outcomes analyzed were: corrected mortality; Apgar scores less than 7 at 5 min; abnormal umbilical cord blood gases; birth trauma; and admissions to the intensive care nursery. Maternal morbidity was also assessed and compared. Results: Of 848 women meeting criteria for evaluation, 576 were delivered by elective cesarean while 272 attempted a vaginal delivery. Of 272 women undergoing a trial of labor, 203 (74.6%) were delivered vaginally, while 69 (25.4%) failed an attempt at vaginal delivery and underwent a cesarean. When comparing patients delivered by elective cesarean with those attempting a vaginal delivery, no significant differences were noted in neonatal outcomes. However, maternal morbidity was higher among women delivered by cesarean, regardless of the indications for the procedure. Similar neonatal and maternal results were noted when nulliparous patients were analyzed separately. Conclusions: Cesarean delivery of selected near‐term infants presenting as breech is associated with increased maternal morbidity without corresponding improvement in neonatal outcomes.

The hemodynamic effects of intravenous digoxin-binding fab immunoglobulin in severe preeclampsia: a double-blind, randomized, clinical trial.

Objective:An endogenous digitalis-like factor (EDLF) has been implicated in the pathophysiology of preeclampsia (PE). This hypothesis is supported by two cases of preeclampsia in which administration of digoxin immune Fab (DIF) reduced mean arterial pressure (MAP).Study Design:To study this observation further, we performed a double-blind, placebo-controlled, randomized clinical trial to examine the effects on MAP of intravenous DIF given after delivery in 26 subjects with severe preeclampsia. Treating obstetricians were blinded to subject assignment and were allowed to use standard antihypertensive drugs during the trial.Results:The primary outcome, a significant difference in blood pressure between the two groups over the 24-h period of observation after the intervention, was not supported. However, mean MAP was significantly lower in the DIF-treated subjects for the first 4 h after therapy as compared with controls (P=0.05). Six subjects (46.2%) in the placebo arm were given conventional antihypertensive medications by their obstetrician for blood pressure >160 mm Hg systolic or >110 mm Hg diastolic, compared with zero subjects in the treatment arm (P=0.01). A trend towards increased creatinine clearance was observed in DIF-treated subjects (137.6±42.6 versus 104.1±43.4, P=0.07).Conclusion:These results support the hypothesis that EDLF contributes to the elevated blood pressure in preeclampsia and suggests a possible role for DIF as a treatment for this condition.

The role of antepartum surveillance in the management of gastroschisis

Objective: To evaluate the perinatal morbidity and mortality of fetuses diagnosed with gastroschisis at our Fetal Diagnosis and Treatment Center. Methods: A retrospective review of a regional prenatal diagnostic center. Twenty‐nine cases of gastroschisis which were diagnosed, managed, delivered and had corrective surgeries through the Fetal Diagnosis and Treatment Center were identified from 1985 to 1994. Perinatal morbidity and mortality were reviewed. Antepartum testing schemes were reviewed when available to determine whether morbidity or mortality could have potentially been prevented. Results: Meconium occurrence, intrauterine growth retardation (IUGR) and oligohydramnios complicated 79%, 41% and 36% of the cases, respectively. The perinatal mortality of this series was 241/1000. Significant differences in perinatal mortality were noted when fetal testing was incorporated (200/1000 vs. 286/1000, P ≤ 0.001). Conclusion: Gastroschisis is associated with a high incidence of IUGR, meconium, oligohydramnios and high perinatal mortality. Antenatal testing appears to significantly lower perinatal mortality in pregnancies complicated by gastroschisis.

CAROLI'S DISEASE COMPLICATING PREGNANCY

We describe two pregnancies in the same patient with Carolis disease (congenital dilatation of the intrahepatic bile ducts). The first pregnancy was uneventful concerning the maternal Carolis disease. The second pregnancy highlights the serious and potentially lethal complications of an acute episode to both the fetus and mother. The patient had acute ascending cholangitis, disseminated intravascular coagulopathy, and septic shock. Fetal distress necessitated delivery by cesarean section. The mothers postoperative course required prolonged critical care and interdisciplinary consultation. Both mother and neonate survived. We present the first report of Carolis disease in pregnancy and review implications to the pregnant patient.

Erythrocyte sodium/potassium ATPase activity in severe preeclampsia.

Objective:Elevated blood levels of endogenous digitalis-like factors (EDLF) may decrease erythrocyte sodium pump activity in preeclampsia. As the highest EDLF levels might be expected in severe preeclampsia, we investigated sodium pump activity in that group of patients.Study Design:Erythrocyte sodium pump activity was determined by 86Rubidium uptake (in nM per hour per 106 cells) in women with severe preeclampsia and those with normal pregnancies, matched for gestational age, and in healthy nonpregnant women (n=12 in each group). Differences between groups were analyzed by a two-sided Student t-test.Result:Sodium pump activity was significantly increased in normotensive pregnancies as compared with normotensive non-pregnant women (81.4±8.4 vs 61.1±7.4, mean±s.d., p<0.05), and was decreased 43% in severe preeclamptic pregnancies as compared with normotensive pregnancies (46.4±14.1 vs 81.4±8.4, p<0.05).Conclusion:Severe preeclampsia is associated with significantly lower erythrocyte sodim pump activity than normotensive pregnancy. These data suggest that plasma levels of a biologically active EDLF are elevated in patients with severe preeclampsia.

Digibind attenuates cytokine TNFα-induced endothelial inflammatory response: potential benefit role of Digibind in preeclampsia

Objective:Exaggerated inflammatory response occurs in preeclampsia. Preeclampsia is also associated with elevated endogenous digoxin-like factors (EDLFs). Clinical data suggest that Digibind (a polyclonal sheep digoxin binding Fab fragment) binds to EDLF and may have the potential to attenuate vasoconstriction and other clinical symptoms of preeclampsia. This study was undertaken to determine if Digibind could attenuate increased endothelial inflammatory response induced by tumor necrosis factor-α (TNFα).Study Design:Confluent endothelial cells were treated with TNFα at different concentrations with or without Digibind in culture. Endothelial adhesion molecule ICAM, VCAM and E-selectin expressions were determined by an immunoassay directly detected on the endothelial surface. Effects of Digibind on TNFα-induced extracellular signal-regulated kinase and Na+/K+-ATPase expressions were also examined.Result:(1) TNFα induced dose-dependent increases in ICAM, VCAM and E-selectin expressions in endothelial cells; (2) Digibind could attenuate and reduce TNFα-induced upregulation of endothelial E-selectin, ICAM and VCAM expressions. The blocking effect was in a concentration dependent manner; (3) Digibind had no effects on TNFα-induced upregulation of extracellular signal-regulated kinase phosphorylation, but could block TNFα-induced downregulation of Na+/K+-ATPase β1 expression.Conclusion:Digibind may exert beneficial effects by preserving cell membrane Na+/K+-ATPase function and consequently to offset increased inflammatory response in endothelial cells.

Repeated dosing of digoxin-fragmented antibody in preterm eclampsia

Early onset eclampsia has significant morbidity and mortality for both the mother and fetus. No effective treatment exists at present except delivery and seizure prophylaxis with magnesium sulfate. We report the novel use of a fragmented ovine antibody against digoxin for the treatment of eclampsia. A 16-year-old primagravida at 29 weeks 5/7 days gestation presented with clinical diagnosis of eclampsia and was treated with compassionate off-label use of digoxin-fragmented ovine antibody (Digibind Glaxo Smith Kline, Research Triangle Park, NC, USA). Improvement of her underlying disorder during a 48 h treatment window was noted without adverse maternal or neonatal outcome. We suggest digoxin-fragmented ovine antibody as a possible intervention in preterm pregnancies complicated by pre-eclampsia or eclampsia.