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

OBJECTIVES: To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth. METHODS: We performed a planned secondary analysis from a large, multinational preterm birth prevention trial of daily intravaginal progesterone gel, 90 mg, compared with placebo in women with a history of spontaneous preterm birth or premature cervical shortening. Transvaginal cervical length measurements were obtained in all randomized patients at baseline (18 + 0 to 22 + 6 weeks' gestation) and at 28 weeks' gestation. For this secondary analysis, the difference in cervical length between these time points was compared for the study population with a history of spontaneous preterm birth and for a population with premature cervical shortening (< or = 30 mm) at randomization. Differences between groups in cervical length for the 28-week examination were analyzed using ANCOVA, including adjustment for relevant clinical parameters and maternal characteristics. RESULTS: Data were analyzed from 547 randomized patients with a history of preterm birth. The progesterone-treated patients had significantly less cervical shortening than the placebo group (difference 1.6 (95% CI, 0.3-3.0) mm; P = 0.02, ANCOVA). In the population of 104 subjects with premature cervical shortening at randomization, the cervical length also differed significantly on multivariable analysis, with the treatment group preserving more cervical length than the placebo group (difference 3.3 (95% CI, 0.3-6.2) mm; P = 0.03, ANCOVA), with adjustment for differences in cervical length at screening. A significant difference was also observed between groups for categorical outcomes including the frequency of cervical length progression to < or = 25 mm and a > or = 50% reduction in cervical length from baseline in this subpopulation. CONCLUSIONS: Intravaginal progesterone enhances preservation of cervical length in women at high risk for preterm birth.

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.

Digibind attenuates cytokine TNFalpha-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-alpha (TNFalpha). STUDY DESIGN: Confluent endothelial cells were treated with TNFalpha 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 TNFalpha-induced extracellular signal-regulated kinase and Na(+)/K(+)-ATPase expressions were also examined. RESULT: (1) TNFalpha induced dose-dependent increases in ICAM, VCAM and E-selectin expressions in endothelial cells; (2) Digibind could attenuate and reduce TNFalpha-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 TNFalpha-induced upregulation of extracellular signal-regulated kinase phosphorylation, but could block TNFalpha-induced downregulation of Na(+)/K(+)-ATPase beta1 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.

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 (86)Rubidium uptake (in nM per hour per 10(6) 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 sodium pump activity than normotensive pregnancy. These data suggest that plasma levels of a biologically active EDLF are elevated in patients with severe preeclampsia.

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.

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.

OBJECTIVE: 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. METHODS: This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at

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

OBJECTIVE: 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. METHODS: This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at

Use of misoprostol on an outpatient basis for postdate pregnancy.

OBJECTIVE: Within the obstetric community, several studies suggest that cervical ripening and labor induction after 40 weeks' gestation leads to improved maternal and neonatal outcomes. The most effective drug regimen to safely promote labor has not been determined. METHOD: Forty-nine subjects followed in an outpatient obstetrical clinic with pregnancies of at least 40 weeks' gestation, and an unfavorable Bishop score were assigned randomly to receive oral misoprostol 50 or 25 microg every 3 days for a maximum of three doses. RESULTS: Twenty-three subjects received misoprostol 25 microg and 26 received 50 microg. The mean interval (+/-standard deviation) from start of cervical ripening to delivery was 2.4 days +/-0.3 vs. 3.9 days +/-0.7 for the 50 and 25 microg groups (P<0.05). No adverse events were noted. However, due to small sample size, less frequent adverse events may be missed. Type II errors cannot be excluded. CONCLUSION: In the prevention of postdate pregnancy, outpatients use of oral misoprostol 50 microg appears to result in earlier delivery, as compared to 25 microg.

Detection of interleukin-6 in maternal plasma predicts neonatal and infectious complications in preterm premature rupture of membranes.

The objective of this study is to determine if the detection of interleukin-6 (IL-6) in maternal plasma prior to delivery predicts neonatal and/or infectious complications in patients with preterm premature rupture of membranes. Patients with preterm premature rupture of membranes between 24 and 35 weeks' gestation were asked to participate in the study. Maternal blood was obtained prior to delivery. All patients received Ampicillin-sulbactam and steroids. IL-6 concentrations were determined by enzyme-linked immunoadsorbent assay (ELISA) using 50 mL of plasma assayed in duplicate. ELISA sensitivity was 18 pg/mL. Neonatal and infectious complications examined were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, intra-amniotic infection, presumed neonatal sepsis, neonatal sepsis, and congenital pneumonia. Fifty-seven patients' plasma was analyzed. Thirty-five had positive plasma IL-6 prior to delivery. Twenty-seven patients had at least one neonatal complication with 24 (89%) being positive for IL-6. Of the 30 patients without complications, only 11 (37%) were positive (p = 0.0001, OR 13.8. 95% CI, 2.93-74.7). A subanalysis of patients who received a course of corticosteroids was performed and significance was maintained. Ten of 13 patients (77%) with neonatal complications had positive IL-6 compared with 40% without complications (p

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.

Nonpharmacologic approaches to cervical priming and labor induction.

Nonpharmacologic and alternative methods of cervical ripening are highly efficacious, safe, and, in general, have more favorable cost advantages when compared with their pharmacologic counterparts. Unfortunately, there have been limited research efforts to precisely determine the overall usefulness and the most clinically efficient application for many of these. These methods also share similar time courses to affect cervical change and are, in general, not as rapid as pharmacologic applications. Thus, limitations of time may ultimately determine the choice between alternative methods and pharmacologic modalities. Most of these alternative methods require more than 12 to 18 hours, and some even days to accomplish favorable changes in the cervix to promote ripening and subsequent labor initiation. These methods have also been shown to be efficient and safe, the most important criteria for any ripening agent, for both the maternal and fetal compartments. These alternative methods will continue to occupy an appropriate place in the armamentarium of cervical ripeners and labor-inducing agents.

A randomized clinical trial of daily nonstress testing versus biophysical profile in the management of preterm premature rupture of membranes.

OBJECTIVE: Our purpose was to evaluate the ability of 2 different antepartum testing modalities to predict infectious morbidity in patients with preterm premature rupture of membranes. STUDY DESIGN: During a 36-month period, patients with preterm premature rupture of membranes (at 23 to 34 weeks of gestation) were randomly assigned to either a daily nonstress test or a biophysical profile, after a 24-hour observational period. We used the original scoring system of Manning et al for the biophysical profile, with a score of

Increased neutrophil-endothelial adhesion induced by placental factors is mediated by platelet-activating factor in preeclampsia.

OBJECTIVE: Endothelial cell activation or dysfunction and neutrophil-endothelial cell adhesion have been suggested to be important in the pathophysiology of preeclampsia. However, the mechanisms that underlie the alteration of endothelial cell function in preeclampsia are unknown. Placenta from preeclamptic pregnancies produces mediators and autacoids, which may be released into the maternal circulation and modulate endothelial function. In this study, the effect of placental factor(s) on neutrophil-endothelial adhesion and the possible role of platelet-activating factor (PAF) in mediating the response have been examined. METHODS: Endothelial cells were isolated from human umbilical veins (HUVECs) from normal pregnancies. Confluent primary passage HUVECs were exposed to conditioned medium derived from normal and preeclamptic placental tissue cultures, with unconditioned medium as a control. Placental-conditioned medium was prepared by incubation of placental whole villous tissue in Dulbecco's Modified Eagle's Medium (DMEM) for 48 hours. Neutrophil-endothelial adhesion assays were performed to evaluate placental factors in mediating neutrophil-endothelial adhesion, and a PAF-3H scintillation proximity assay (SPA) system was used to determine endothelial PAF production. The PAF-receptor antagonist WEB 2086 was used to block placental factor-mediated increased neutrophil-endothelial adhesion induced by conditioned medium derived from preeclamptic placenta. RESULTS: Neutrophils were significantly more adherent to HUVECs treated with conditioned medium from preeclamptic placentas (28.44 +/- 2.47%) than to HUVECs treated with conditioned medium from normal placentas (18.95 +/- 1.57%) or with unconditioned medium (14.60 +/- 1.29%, P < .01). Also, HUVECs exposed to preeclamptic placental-conditioned medium produced more PAF than the cells exposed to normal conditioned medium and unconditioned medium, 416.18 +/- 17.14 pg/1 x 10(7) cells versus 330.90 +/- 35.70 and 296.43 +/- 44.40 pg/1 x 10(7) cells, P < .05, respectively. The PAF receptor antagonist WEB 2086 completely blocked increased neutrophil-endothelial adhesion induced by preeclamptic placental-conditioned medium (13.24 +/- 0.81% versus 31.31 +/- 4.75%, P < .01). CONCLUSION: In preeclampsia, the placenta releases one or more factors promoting neutrophil-endothelial adhesion. The increased neutrophil-endothelial adhesion thereby induced is a PAF-mediated event. It is suggested that if preeclamptic placentas release toxic factors into the maternal circulation in vivo, these factors may contribute to the altered vascular endothelial cell function in preeclampsia.

Interleukin-8 stimulates placental prostacyclin production in preeclampsia.

PROBLEM: Our purpose was to determine placental interleukin (IL)-8 production and its correlation with the prostacyclin production in normal and preeclamptic pregnancies and to evaluate the beneficial effect of IL-8 on prostacyclin production. METHOD OF STUDY: We determined 1) the in vitro production of IL-8 and prostacyclin by placental villous tissues from normal and preeclamptic pregnancies and 2) the production of prostacyclin by villous tissues from preeclampsia treated with recombinant human IL-8 (rhIL-8). IL-8 levels were measured by enzyme-linked immunosorbent assay and prostacyclin by radioimmunoassay of 6-keto PGF1alpha, the stable metabolite of prostacyclin. RESULTS: 1) Placental production of IL-8 and 6-keto PGF1alpha were significantly less in preeclampsia than in normal pregnancies, P<0.05. 2) Placental production of 6-keto PGF1alpha and IL-8 was significantly correlated in preeclampsia, P<0.01. 3) Placental tissues treated with IL-8 exhibited a concentration-dependent increase in 6-keto PGF1alpha production. CONCLUSIONS: Placental tissues from preeclampsia produce significantly less IL-8 than tissues from normal pregnancies, which correlates with decreased prostacyclin production. IL-8 improves placental prostacyclin production in preeclampsia.

Oral or vaginal misoprostol administration for induction of labor: a randomized, double-blind trial.

OBJECTIVE: To compare the efficacy and vaginal birth intervals after intravaginal or oral misoprostol for labor induction. METHODS: One hundred seventy-eight women were randomized to one of two double-blind groups: 1) oral misoprostol 200 microg and one-half tablet placebo intravaginal or 2) oral placebo tablet and one-half tablet of a 100-microg misoprostol intravaginal (dose 50 microg). Doses were repeated every 6 hours until labor was established (maximum of three doses). RESULTS: Ninety-three subjects were assigned to oral misoprostol and 85 to intravaginal administration. Oral administration was accompanied by significantly shorter intervals to the onset of uterine contractility (133+/-78 minutes versus 168+/-93, P < .01) but a higher incidence of abnormal uterine contractile activity (tachysystole 38.7% versus 20.0%, P < .01; hyperstimulation syndrome 44.1% versus 21.2%, P < .01). No adverse maternal or neonatal outcomes were noted, nor were there differences in cesarean delivery rates or total lengths of labor. CONCLUSION: Oral administration of 200 microg misoprostol has similar efficacy to intravaginal administration of 50 microg but is associated with more frequent abnormal uterine contractility.

Activation of endothelial cells in preeclampsia: increased neutrophil-endothelial adhesion correlates with up-regulation of adhesion molecule P-selectin in human umbilical vein endothelial cells isolated from preeclampsia.

OBJECTIVE: Increased endothelial activation has been suggested to be important in the pathophysiology for preeclampsia. Our objective was to examine whether in preeclampsia neutrophil adherence to endothelial cells is increased and whether endothelial cell-surface adhesion molecule expression is up-regulated. METHODS: Endothelial cells were isolated from normal (n = 10) and preeclamptic (n = 9) human umbilical veins (HUVECs). Neutrophils were isolated from normal, healthy, nonpregnant female volunteers. Freshly isolated neutrophils were labeled with 51Cr, and labeled neutrophils were coincubated with confluent normal and preeclamptic endothelial monolayers. Adhesion assays were then performed. To determine whether in preeclampsia endothelial cellular-surface adhesion molecules are responsible for increased neutrophil-endothelial adhesion, cellular adhesion molecule expression of P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin were examined by an enzyme-linked binding assay. Furthermore, adhesion assays were also performed on HUVECs pretreated with antibodies against P-selectin, ICAM-1, VCAM-1, and E-selectin. RESULTS: Neutrophil adhesion to the HUVECs from preeclamptic pregnancies was significantly increased compared with neutrophil adhesion to the HUVECs from normal pregnancies (P < .01). Expression of cellular-surface adhesion molecule of P-selectin was significantly higher (P < .01) and ICAM-1 was significantly lower (P < .05) in HUVECs isolated from preeclampsia than from normal controls, whereas there was no difference for VCAM-1 and E-selectin expression between HUVECs from normal and preeclamptic pregnancies. No differences were found for neutrophil-endothelial adhesion on normal HUVECs pretreated with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin compared with the untreated cells. However, pretreatment of preeclampsia HUVECs with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin completely or partially blocked the neutrophil-endothelial adhesion compared to the untreated cells. CONCLUSION: There is a significant increase in neutrophil adhesion to HUVECs that are isolated from preeclamptic pregnancies compared with normal controls. This increase appears to be a result of up-regulation of the cell-surface adhesion molecule P-selectin. Elevated P-selectin expression may play a significant role in neutrophil-endothelial hyperadhesiveness and contribute to vascular complications associated with preeclampsia.

Can shoulder dystocia be predicted? Preconceptive and prenatal factors.

OBJECTIVE: To evaluate the predictability of shoulder dystocia using preconceptive and prenatal risk factors. STUDY DESIGN: Data from 1,622 term patients with prenatal care prior to 20 weeks who delivered single, vertex fetuses during a consecutive 12-month period were analyzed. Two groups were chosen. The first group was patients whose fetuses experienced shoulder dystocia during delivery (cases). The second group (controls) consisted of the remaining patients, whose fetuses had not experienced shoulder dystocia. The two groups were compared with regard to demographics and pregnancy characteristics. RESULTS: Factors not significantly different between the two groups included were obesity, multiparity, history of diabetes, short maternal stature, postdatism and advanced maternal age. The incidence of macrosomia was significantly higher (P < .001) in cases (35.4%) than in controls (4.8%). Other factors associated with shoulder dystocia were previous shoulder dystocia, concurrent diabetes, prior delivery of a fetus > 4,000 g and excessive weight gain during pregnancy. Many factors previously associated with shoulder dystocia were found to be nonsignificant in our study. CONCLUSION: Macrosomia appears to be the single important factor associated with shoulder dystocia which, even in the presence of significant risk factors, remains largely unpredictable.

Obstructive sleep apnea during pregnancy resulting in pulmonary hypertension.

Obesity is known to increase maternal morbidity and mortality. We describe a case of obstructive sleep apnea due to obesity and discuss our treatment of the resulting pulmonary hypertension. A patient was transferred to our hospital at 29 weeks' gestation with severe anasarca and more than a 100-pound weight gain during pregnancy. Pulmonary hypertension due to obstructive sleep apnea was diagnosed. The patient was treated with nasal continuous positive airway pressure (CPAP) during sleep and remained in the hospital the remainder of her pregnancy. She had a massive spontaneous diuresis during her hospital stay and lost more than 100 pounds. She was delivered at term via cesarean section because of transverse lie. Preoperative hemodynamic monitoring confirmed the diagnosis of pulmonary hypertension. This represents the first case in the literature of obstructive sleep apnea leading to pulmonary hypertension in pregnancy. This patient responded well to nasal CPAP as evident by the massive diuresis and good maternal outcome.

Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin.

OBJECTIVE: To determine side effect profiles and cure rates of azithromycin compared with erythromycin in the treatment of chlamydial cervicitis complicating pregnancy. METHODS: Pregnant patients with positive DNA antigen assays for Chlamydia trachomatis were randomized to either azithromycin, 1 g oral slurry in a single dose, or erythromycin, 500 mg every 6 hours for 7 days. Repeat assays were planned for 3 weeks after therapy. Side effects, compliance, and treatment efficacy were assessed. RESULTS: One hundred six women were enrolled, and eighty-five women completed the protocol. Significantly fewer gastrointestinal side effects were noted in the azithromycin group than in the erythromycin group (11.9% versus 58.1%, P < or = .01). Enhanced compliance was noted with azithromycin, because it was given in a single observed dose. Similar treatment efficacy was noted between azithromycin and erythromycin (88.1% versus 93.0%, P > .05). CONCLUSION: Compared with erythromycin, azithromycin is associated with significantly fewer gastrointestinal side effects in pregnancy. This association, along with the ease of administration and similar efficacy, suggests that azithromycin should be considered for the initial treatment of chlamydial cervicitis in pregnancy.

Successful magnesium sulfate tocolysis: is "weaning" the drug necessary?

OBJECTIVE: Magnesium sulfate is the most commonly used tocolytic agent for preterm labor. A common clinical practice is to slowly discontinue the drug (wean) after successful tocolysis. Our objective was to determine the necessity of this practice. STUDY DESIGN: A prospective, randomized clinical trial was performed from June 1993 to July 1996. After successful magnesium sulfate tocolysis, patients with preterm labor were randomized to two groups: stopping the drug abruptly (no weaning) or gradually weaning the drug (approximately 1 gm every 4 hours). Preterm labor was defined as documented cervical change with regular uterine contractions or regular uterine contractions with a cervix of 2 cm and 75% effacement. The primary outcome variable was the necessity to reinstitute magnesium sulfate therapy within 24 hours of discontinuation of successful tocolysis. RESULTS: One hundred forty-one patients completed the study. No patient in the no-wean group required retocolysis within 24 hours of magnesium discontinuation. However, eight patients in the wean group required retocolysis within 24 hours of magnesium discontinuation (p = 0.01). Significantly more patients in the wean group had retocolysis during pregnancy (3 vs 12, p = 0.03). Patients in the wean group were also in the labor and delivery unit longer and, as would be anticipated, received magnesium sulfate significantly longer. No differences in the neonatal outcomes were noted between the two groups. Seventy-seven percent of the patients in the study were delivered prematurely. CONCLUSION: This study demonstrated an increased need for retocolysis in the group weaned from magnesium sulfate. We also found that patients in the wean group had an increased labor and delivery time and a longer administration time of magnesium sulfate. Thus weaning magnesium sulfate increases health care cost. The practice of weaning magnesium sulfate does not appear beneficial.